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Clinical Trial Results:
A Phase III, randomized, multicenter, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of switching to dolutegravir plus lamivudine in HIV-1 infected adults who are virologically suppressed

Summary
EudraCT number	2015-004401-17
Trial protocol	DE GB ES BE NL
Global end of trial date	03 May 2022

Results information
Results version number	v6(current)
This version publication date	02 Aug 2023
First version publication date	02 May 2020
Other versions	v1 , v2 , v3 , v4 , v5
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

204862

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

ViiV Healthcare

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS

Public contact

GSK Response Center, ViiV Healthcare, 1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, ViiV Healthcare, 1 8664357343, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

27 Jun 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 May 2022

Was the trial ended prematurely?

Main objective of the trial

To demonstrate the non-inferior antiviral activity of switching to DTG +3TC once daily compared to continuation of TBR over 48 weeks in HIV-1 infected, ART therapy (ART)-experienced, virologically suppressed participants.

Protection of trial subjects

Not Applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

18 Jan 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 40

Country: Number of subjects enrolled

Belgium: 25

Country: Number of subjects enrolled

Canada: 25

Country: Number of subjects enrolled

France: 26

Country: Number of subjects enrolled

Germany: 83

Country: Number of subjects enrolled

Japan: 11

Country: Number of subjects enrolled

Netherlands: 5

Country: Number of subjects enrolled

Spain: 229

Country: Number of subjects enrolled

United States: 286

Country: Number of subjects enrolled

United Kingdom: 13

Worldwide total number of subjects

743

EEA total number of subjects

368

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

726

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study evaluated antiviral activity of switching to dolutegravir(DTG)+lamivudine(3TC) fixed dose combination(FDC) once daily compared to continuation of Tenofovir alafenamide (TAF)-based regimen(TBR)over 148weeks in participants with human immunodeficiency type 1 infection. At week148 all participants received DTG+3TC FDC until week 196.

Screening details

A total of 743 participants were randomized to receive treatment. Two participants in the DTG+3TC group were randomized but not treated. A total of 741 participants received at least one dose of study treatment either DTG + 3TC or TBR creating the intent to treat-exposed (ITT-E) Population.

Period 1 title

Early Switch Phase (Day 1 to week 148)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

DTG+3TC FDC

Arm description

Participants who were on a stable TBR and who had an HIV-1 ribonucleic acid (RNA) less than (<)50 copies per millilter (c/mL) at the time of screening, received fixed dose combination of DTG 50 milligrams (mg) + 3TC 300 mg in early switch phase (Day 1 to Week 148) and continued to receive DTG/3TC FDC in late switch phase (Week 148 to Week 196).

Arm type

Experimental

Investigational medicinal product name

Dolutegravir (DTG)+Lamivudine (3TC) fixed dose combination (FDC)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants received DTG 50 milligrams (mg) + 3TC 300 mg FDC as a white, oval and film-coated tablet. The tablets were packed in high density polyethylene (HDPE) bottles with induction seals, 2 grams (gm) desiccant, and child resistant closures. Each 60 milliliter (mL) bottle contains 30 tablets.

TAF-based regimen

Arm description

Participants who were on a stable TBR and had an HIV-1 RNA<50 c/mL at the time of screening received TBR up to Week 148 in early switch phase, these participants were switched to DTG/3TC FDC in late switch phase (Week 148 to Week 196). One participant randomized to this arm received TDF rather than TAF-and was presented within the "TAF-based regimen" arm (early switch phase) for efficacy because the efficacy of TAF and TDF are comparable. However, the participant was presented separately under "TDF-based regimen"arm (early switch phase) for Safety because the safety profiles of TDF and TAF differ.

Arm type

Active comparator

Investigational medicinal product name

Tenofovir alafenamide (TAF) based regimen (TBR)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants continued to receive stable TBR

Number of subjects in period 1 ^[1]	DTG+3TC FDC	TAF-based regimen
Started	369	372
Completed	319	299
Not completed	50	73
Adverse event, serious fatal	3	-
Physician decision	2	11
Consent withdrawn by subject	16	33
Adverse event, non-fatal	20	7
Lost to follow-up	4	10
Protocol deviation	5	6
Lack of efficacy	-	6

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: One participant was not switched to DTG+ 3TC FDC due to being lost to follow up post Week 148 visit, hence did not enter in the late switch phase

Period 2 title

Late Switch Phase (Week 148 to Week 196)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

DTG+3TC FDC

Arm description

Arm type

Experimental

Investigational medicinal product name

Dolutegravir (DTG)+Lamivudine (3TC) fixed dose combination (FDC)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

TAF-based regimen

Arm description

Arm type

Active comparator

Investigational medicinal product name

Tenofovir alafenamide (TAF) based regimen (TBR)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Participants continued to receive stable TBR

Number of subjects in period 2 ^[2]	DTG+3TC FDC	TAF-based regimen
Started	319	298
Completed	307	274
Not completed	12	24
Adverse event, serious fatal	1	-
Consent withdrawn by subject	4	6
Physician decision	-	1
Adverse event, non-fatal	1	9
Lost to follow-up	5	6
Lack of efficacy	1	1
Protocol deviation	-	1

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: A total of 743 participants were enrolled, of which two participants did not receive treatment and hence 741 participants received at least one treatment in the study.

Baseline characteristics

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Reporting group title

DTG+3TC FDC

Reporting group description

Reporting group title

TAF-based regimen

Reporting group description

Reporting group values	DTG+3TC FDC	TAF-based regimen	Total
Number of subjects	369	372	741
Age categorical
Baseline Characteristic data are reported for participants in the ITT-E Population
Units: Subjects
Total	369	372	741
Age Continuous
Baseline Characteristic data are reported for participants in the ITT-E Population
Units: years
arithmetic mean (standard deviation)	40.6 ( 10.76 )	40.9 ( 11.54 )	-
Sex: Female, Male
Baseline Characteristic data are reported for participants in the ITT-E Population
Units: Participants
Female	25	33	58
Male	344	339	683
Race/Ethnicity, Customized
Baseline Characteristic data are reported for participants in the ITT-E Population
Units: Subjects
American Indian or Alaska Native	7	8	15
Asian-Central/South Asian Heritage (H)	3	4	7
Asian-Japanese H/East Asian H/South East Asian H	10	9	19
Black or African American	50	58	108
Native Hawaiian or other Pacific Islander	1	3	4
White-Arabic/North African (NA) H	5	2	7
White-Arabic/NA H and white/caucasia/European H	0	1	1
White-White/caucasian/European H	292	286	578
Asian and White	0	1	1
Black or African American and White	1	0	1
HIV infection by Centers for Disease Control and Prevention (CDC) classification
CDC classification for human immunodeficiency (HIV) were: Stage 1: No acquired immuno deficiency syndrome (AIDS) defining condition and CD4+ T-lymphocyte count: >=500 cells per microliter (cells/mcL); Stage 2: No AIDS-defining condition and CD4 200-499; Stage 3: Documentation of an AIDS- defining condition or CD4 < 200cells/mcL. Baseline Characteristic data are reported for participants in the ITT-E Population
Units: Subjects
HIV infection Stage 1	255	259	514
HIV infection Stage 2	94	94	188
HIV infection Stage 3	20	19	39
Baseline third agents
Baseline third agents including non-nucleoside reverse transcriptase inhibitors (NNRTI), integrase strand transfer inhibitors (INSTI) and protease inhibitors (PIs) based on the antiretroviral medications taken at Baseline. Baseline Characteristic data are reported for participants in the ITT-E Population
Units: Subjects
NNRTI	51	48	99
INSTI	289	296	585
PIs	29	28	57
Cluster of differentiation 4 plus (CD4+) cell count
Blood samples were collected to evaluate Baseline CD4+ cell count using flow cytometry. Median along with first and third quartiles are presented for Baseline CD4+ count. Baseline Characteristic data are reported for participants in the ITT-E Population
Units: Cells per cubic millimeter (cells/mm^3)
median (inter-quartile range (Q1-Q3))	682.0 (492.0 to 862.0)	720.0 (531.5 to 901.5)	-

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who were on a stable TBR and who had an HIV-1 ribonucleic acid (RNA) <50 copies per millilter (c/mL) at the time of screening, received fixed dose combination of DTG 50 milligrams (mg) + 3TC 300 mg once daily up to 148 weeks during early switch phase.

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who were on a stable TBR and who had an HIV-1 RNA<50 c/mL at the time of screening, were continued to receive TBR up to 148 weeks during early switch phase. One participant randomized to the TAF-based regimen arm received TDF rather than TAF-and was presented within the "TAF-based regimen" arm for efficacy because the efficacy of TAF and TDF are comparable. However, the participant was presented separately under "TDF-based regimen" for Safety because the safety profiles of TDF and TAF differ.

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Randomized to TBR But Received TDF-based Regimen(Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participant randomized to TBR arm who had HIV-1 RNA <50 c/mL at the time of screening, received TDF-based regimen instead of TAF-based regimen in error. Participant continued to receive TDF-regimen up to the Week 48 visit (participant withdrew from the study at Week 36)

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Randomized to TBR But Received TDF-based Regimen(Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants who were on a stable TBR and who had an HIV-1 RNA<50 c/mL at the time of screening, were continued to receive TBR up to 48 weeks. One participant randomized to the this arm received TDF rather than TAF-and was presented within the “TAF-based regimen” arm for efficacy because the efficacy of TAF and TDF are comparable. However the participant was presented separately under “TDF-based regimen” for Safety because the safety profiles of TDF and TAF differ.

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early Switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

DTG+3TC FDC (Early switch)

TAF Based Regimen (Early switch)

DTG+3TC FDC (Early switch)

TAF Based Regimen (Early switch)

DTG+3TC FDC (Early switch)

TAF Based Regimen (Early switch)

DTG+3TC FDC (Early switch)

TAF Based Regimen (Early switch)

Randomized to TBR But Received TDF-based Regimen(Early switch)

DTG+3TC FDC (Early switch)

Randomized to TBR But Received TDF-based Regimen(Early switch)

DTG+3TC FDC (Early switch)

TAF Based Regimen (Early switch)

TAF Based Regimen (Early Switch)

DTG+3TC FDC (Early switch)

TAF Based Regimen (Early switch)

Number of subjects

369

372

344

346

369

372

350

358

371

369

371

364

370

369

Baseline Characteristic data are reported for participants in the ITT-E Population

Units: Subjects

Total

Baseline Characteristic data are reported for participants in the ITT-E Population

Units: years

arithmetic mean (standard deviation)

0.3 ( )

0.5 ( )

93.2 ( )

93.0 ( )

( )

95 ( )

96 ( )

( )

23 ( )

0 ( )

( )

Baseline Characteristic data are reported for participants in the ITT-E Population

Units: Participants

Female

Male

Baseline Characteristic data are reported for participants in the ITT-E Population

Units: Subjects

American Indian or Alaska Native

Asian-Central/South Asian Heritage (H)

Asian-Japanese H/East Asian H/South East Asian H

Black or African American

Native Hawaiian or other Pacific Islander

White-Arabic/North African (NA) H

White-Arabic/NA H and white/caucasia/European H

White-White/caucasian/European H

Asian and White

Black or African American and White

CDC classification for human immunodeficiency (HIV) were: Stage 1: No acquired immuno deficiency syndrome (AIDS) defining condition and CD4+ T-lymphocyte count: >=500 cells per microliter (cells/mcL); Stage 2: No AIDS-defining condition and CD4 200-499; Stage 3: Documentation of an AIDS- defining condition or CD4 < 200cells/mcL. Baseline Characteristic data are reported for participants in the ITT-E Population

Units: Subjects

HIV infection Stage 1

HIV infection Stage 2

HIV infection Stage 3

Baseline third agents including non-nucleoside reverse transcriptase inhibitors (NNRTI), integrase strand transfer inhibitors (INSTI) and protease inhibitors (PIs) based on the antiretroviral medications taken at Baseline. Baseline Characteristic data are reported for participants in the ITT-E Population

Units: Subjects

NNRTI

INSTI

PIs

Blood samples were collected to evaluate Baseline CD4+ cell count using flow cytometry. Median along with first and third quartiles are presented for Baseline CD4+ count. Baseline Characteristic data are reported for participants in the ITT-E Population

Units: Cells per cubic millimeter (cells/mm^3)

median (inter-quartile range (Q1-Q3))

0.3 ( to )

0.5 ( to )

93.2 ( to )

93.0 ( to )

95 ( to )

96 ( to )

23 ( to )

0 ( to )

End points

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Reporting group title

DTG+3TC FDC

Reporting group description

Reporting group title

TAF-based regimen

Reporting group description

Reporting group title

DTG+3TC FDC

Reporting group description

Reporting group title

TAF-based regimen

Reporting group description

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Randomized to TBR But Received TDF-based Regimen(Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Randomized to TBR But Received TDF-based Regimen(Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early Switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG+3TC FDC (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

TAF Based Regimen (Early switch)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Primary: Percentage of participants with virologic failure endpoint as per Food and Drug Administration (FDA) snapshot category at Week 48

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End point title

Percentage of participants with virologic failure endpoint as per Food and Drug Administration (FDA) snapshot category at Week 48

End point description

Percentage of participants with virologic failure (plasma HIV-1 RNA >=50 c/mL) was evaluated using FDA snapshot algorithm at Week 48. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest. Intent-to-treat exposed (ITT-E) Population comprises of all randomized participants who received at least one dose of study treatment either DTG + 3TC or TBR. Participants were assessed according to the treatment to which the participant was randomized. Any participant receiving a treatment randomization number was considered to be randomized. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable.

End point type

Primary

End point timeframe

Week 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[1]	372 ^[2]
Units: Percentage of participants
number (not applicable)	0.3	0.5

Notes
[1] - ITT-E Population.
[2] - ITT-E Population.

Statistical Analysis

Statistical analysis description

ADP was based on Cochran-Mantel Haenszel stratified analysis adjusting for Baseline stratification factor:Baseline third agent (protease inhibitor [PI], non-nucleoside reverse transcriptase inhibitor [NNRTI], and integrase inhibitor [INI]).

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

741

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Adjusted difference in proportion (ADP)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.7

Notes
[3] - Non-inferiority of switching to DTG + 3TC compared to continuation of TBR (as per FDA snapshot algorithm) was to be concluded if the upper bound of a two-sided 95% confidence interval (CI) for the difference in virologic failure rates between the two treatment arms was smaller than 4%.

Secondary: Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Week 48

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End point title

Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Week 48

End point description

Percentage of participants with plasma HIV-1 RNA <50 c/mL (virologic success) was evaluated using FDA snapshot algorithm at Week 48 to demonstrate the non-inferior antiviral activity of switching to DTG +3TC once daily compared to continuation of TBR over 48 weeks. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. Only those participants with data available at specified time points has been analyzed. One participant randomized to TBR but received TDF-based regimen and was presented within the "TBR (TAF-based regimen) arm" as efficacy of TAF and TDF are comparable.

End point type

Secondary

End point timeframe

Week 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	344 ^[4]	346 ^[5]
Units: Percentage of participants
number (not applicable)	93.2	93.0

Notes
[4] - ITT-E Population.
[5] - ITT-E Population.

Statistical Analysis 1

Statistical analysis description

ADP was based on Cochran-Mantel Haenszel stratified analysis adjusting for Baseline stratification factor: Baseline third agent (PI, NNRTI, and INSTI).

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

690

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

Method

Parameter type

Adjusted difference in proportion

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.9

Notes
[6] - Non-inferiority of switching to DTG + 3TC compared to continuation of TBR (as per FDA snapshot algorithm) was to be concluded when the lower bound of a 2-sided 95% confidence interval for the difference in success rates between the two treatment arms was greater than -8%.

Secondary: Percentage of participants with virologic failure endpoint as per FDA snapshot category at Week 24

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End point title

Percentage of participants with virologic failure endpoint as per FDA snapshot category at Week 24

End point description

Percentage of participants with plasma HIV-1 RNA >=50 c/mL was evaluated using FDA snapshot algorithm at Week 24. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. One participant randomized to TBR but received TDF-based regimen and was presented within the "TBR (TAF-based regimen) arm" as efficacy of TAF and TDF are comparable.

End point type

Secondary

End point timeframe

Week 24

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[7]	372 ^[8]
Units: Percentage of participants
number (not applicable)	0.3	0.8

Notes
[7] - ITT-E Population.
[8] - ITT-E Population.

No statistical analyses for this end point

Secondary: Percentage of participants with virologic failure endpoint as per FDA snapshot category at Weeks 96, 144

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End point title

Percentage of participants with virologic failure endpoint as per FDA snapshot category at Weeks 96, 144

End point description

Percentage of participants with plasma HIV-1 RNA >=50 c/mL was evaluated using FDA snapshot algorithm at Weeks 96 and 144. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable.

End point type

Secondary

End point timeframe

Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[9]	372 ^[10]
Units: Percentage of participants
number (not applicable)
Week 96	0.3	1.1
Week 144	0.3	1.3

Notes
[9] - ITT-E Population
[10] - ITT-E Population

No statistical analyses for this end point

Secondary: Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Week 24

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End point title

Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Week 24

End point description

Percentage of participants with plasma HIV-1 RNA <50 c/mL was evaluated using FDA snapshot algorithm at Week 24. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. Only those participants with data available at specified time points has been presented. One participant randomized to TBR but received TDF-based regimen and was presented within the "TBR (TAF-based regimen) arm" as efficacy of TAF and TDF are comparable. Percentage values are rounded off.

End point type

Secondary

End point timeframe

Week 24

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	350 ^[11]	358 ^[12]
Units: Percentage of participants	95	96

Notes
[11] - ITT-E Population.
[12] - ITT-E Population.

No statistical analyses for this end point

Secondary: Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Weeks 96 and 144

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End point title

Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Weeks 96 and 144

End point description

Percentage of participants with plasma HIV-1 RNA <50 c/mL was evaluated using FDA snapshot algorithm at Weeks 96 and 144. Only those participants with data available at specified time points has been analyzed.

End point type

Secondary

End point timeframe

Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[13]	372 ^[14]
Units: Percentage of participants
number (not applicable)
Week 96	85.9	79.0
Week 144	85.9	81.7

Notes
[13] - ITT-E Population.
[14] - ITT-E Population.

No statistical analyses for this end point

Secondary: Change from Baseline in CD4+ cell count at Weeks 24 and 48

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End point title

Change from Baseline in CD4+ cell count at Weeks 24 and 48

End point description

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable. All 741 (369+372) participants were analyzed, however only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[15]	372 ^[16]
Units: Cells per cubic millimeter
median (inter-quartile range (Q1-Q3))
Week 24, n=351, 359	21.0 (-68.0 to 115.0)	6.0 (-87.0 to 99.0)
Week 48, n=344, 345	22.5 (-71.0 to 121.5)	11.0 (-98.0 to 90.0)

Notes
[15] - ITT-E Population.
[16] - ITT-E Population.

No statistical analyses for this end point

Secondary: Change from Baseline in CD4+/CD8+ cell count ratio at Weeks 24 and 48

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End point title

Change from Baseline in CD4+/CD8+ cell count ratio at Weeks 24 and 48

End point description

Blood samples were collected at specified time points to assess CD4+/CD8+ cell count ratio. It was assessed by flow cyclometry to evaluate the immunologic activity of switching to DTG+3TC once daily compared to continuation of TBR over 48 Weeks. Baseline (Day 1) values were the actual CD4+ cell count ratio values at pre-dose Day 1. Change from Baseline is defined as post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable . All 741 (369+372) participants were analyzed, however only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[17]	372 ^[18]
Units: Ratio
median (inter-quartile range (Q1-Q3))
Week 24, n=346, 358	0.010 (-0.070 to 0.110)	0.040 (-0.060 to 0.120)
Week 48, n=342, 343	0.030 (-0.050 to 0.110)	0.050 (-0.050 to 0.160)

Notes
[17] - ITT-E Population.
[18] - ITT-E Population.

No statistical analyses for this end point

Secondary: Change from Baseline in CD4+/CD8+ cell count ratio at Weeks 96 and 144

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End point title

Change from Baseline in CD4+/CD8+ cell count ratio at Weeks 96 and 144

End point description

Blood samples were collected at specified time points to assess CD4+/CD8+ cell count ratio and were evaluated by flow cyclometry to evaluate the immunologic activity of switching to DTG+3TC once daily compared to continuation of TBR over Weeks 96 and 144. Baseline (Day 1) values are the actual CD4+ cell count ratio values at pre-dose Day 1. Change from Baseline is defined as post-dose visit value minus Baseline value. All 741 (369+372) participants were analyzed, however only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[19]	372 ^[20]
Units: Ratio
median (inter-quartile range (Q1-Q3))
Week 96, n=312, 292	0.035 (-0.085 to 0.140)	0.080 (-0.050 to 0.170)
Week 144, n=307, 300	0.060 (-0.060 to 0.200)	0.100 (-0.020 to 0.240)

Notes
[19] - ITT-E Population.
[20] - ITT-E Population.

No statistical analyses for this end point

Secondary: Change from Baseline in CD4+ cell count at Weeks 96 and 144

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End point title

Change from Baseline in CD4+ cell count at Weeks 96 and 144

End point description

CD4+ cells are a type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+and evaluated by flow cytometry. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. All 741 (369+372) participants were analyzed, however only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[21]	372 ^[22]
Units: Cells per cubic millimeter
median (inter-quartile range (Q1-Q3))
Week 96, n=315, 295	61.0 (-61.0 to 179.0)	45.0 (-80.0 to 154.0)
Week 144, n=309, 301	36.0 (-64.0 to 154.0)	35.0 (-60.0 to 134.0)

Notes
[21] - ITT-E Population.
[22] - ITT-E Population.

No statistical analyses for this end point

Secondary: Number of participants with disease progression at Weeks 24 and 48

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End point title

Number of participants with disease progression at Weeks 24 and 48

End point description

HIV-associated conditions were recorded during the study and were assessed according to the 2014 CDC Classification System for HIV Infection in Adults. CDC classification for HIV were: Stage 1: No AIDS defining condition and CD4+ T-lymphocyte count: >=500 cells/mcL; Stage 2: No AIDS infection and CD4+ lymphocyte count: 200-499 cell/mcL and Stage 3:Documented AIDS defining condition or CD4+ T-lymphocye count <200 cells/mcL. Disease progression summarize participants who had HIV infection stage 3 associated conditions or death. Indicators of clinical disease progression were defined as: CDC Category Stage 1 at enrollment to Stage 3 event; CDC Category Stage 2 at enrollment to Stage 3 event; CDC Category Stage 3 at enrollment to New Stage 3 Event; CDC Category Stage 1, 2 or 3 at enrollment to Death. One participant randomized to TBR but received TDF-based regimen and was presented within the "TBR (TAF-based regimen) arm" as efficacy of TAF and TDF are comparable

End point type

Secondary

End point timeframe

At Weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[23]	372 ^[24]
Units: Participants
From CDC Stage 1 to CDC Stage 3 Event	1	0
From CDC Stage 2 to CDC Stage 3 Event	0	0
From CDC Stage 3 to new CDC Stage 3 Event	0	0
From CDC Stage 1, 2 or 3 to Death	1	0
No HIV-1 disease progression	367	372

Notes
[23] - ITT-E Population.
[24] - ITT-E Population.

No statistical analyses for this end point

Secondary: Number of participants with disease progression at Weeks 96 and 144

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End point title

Number of participants with disease progression at Weeks 96 and 144

End point description

HIV-associated conditions were recorded during the study and assessed according to the 2014 CDC Classification System for HIV Infection in Adults. CDC classification for HIV is: Stage 1: No AIDS defining condition and CD4+ T-lymphocyte count: >=500 cells/mcL; Stage 2: No AIDS infection and CD4+ lymphocyte count: 200-499 cell/mcL and Stage 3: Documented AIDS-defining condition or CD4+ T-lymphocye count <200 cells/mcL. Indicators of clinical disease progression is defined as: CDC Category Stage 1 at enrollment to Stage 3 event; CDC Category Stage 2 at enrollment to Stage 3 event; CDC Category Stage 3 at enrollment to New Stage 3 Event; CDC Category Stage 1, 2 or 3 at enrollment to Death. One participant randomized to TBR but received TDF-based regimen and was presented within the "TBR (TAF-based regimen) arm" as efficacy of TAF and TDF are comparable

End point type

Secondary

End point timeframe

At Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[25]	372 ^[26]
Units: Participants
Week 96, From CDC Stage 1 to CDC Stage 3 Event	2	0
Week 96, From CDC Stage 2 to CDC Stage 3 Event	0	0
Week 96, From CDC Stage 3 to new CDC Stage 3 Event	0	0
Week 96, From CDC Stage 1, 2 or 3 to Death	2	0
Week 96, No HIV-1 disease progression	365	372
Week 144, From CDC Stage 1 to CDC Stage 3 Event	2	0
Week 144, From CDC Stage 2 to CDC Stage 3 Event	0	1
Week 144,From CDC Stage 3 to new CDC Stage 3 Event	0	0
Week 144, From CDC Stage 1, 2 or 3 to Death	3	0
Week 144, No HIV-1 disease progression	364	371

Notes
[25] - ITT-E Population.
[26] - ITT-E Population.

No statistical analyses for this end point

Secondary: Number of participants with any serious adverse events (SAEs) and common (>=2%) non-serious adverse events (non-SAEs): Up to Week 48

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End point title

Number of participants with any serious adverse events (SAEs) and common (>=2%) non-serious adverse events (non-SAEs): Up to Week 48

End point description

An AE is any untoward medical occurrence temporally associated with use of a study treatment, whether or not considered related to study treatment. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other important medical event as per medical or scientific judgment. Number of participants with any SAE and common (>=2%) non-SAEs are presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[27]	371 ^[28]
Units: Participants
Any non-SAE (>=2%)	222	204
Any SAE	21	16

Notes
[27] - Safety Population.
[28] - Safety Population.

No statistical analyses for this end point

Secondary: Number of Participants with AEs by their severity Grades: Up to Week 48

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End point title

Number of Participants with AEs by their severity Grades: Up to Week 48

End point description

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[29]	371 ^[30]
Units: Participants
Grade 1	102	94
Grade 2	170	177
Grade 3	19	15
Grade 4	3	6
Grade 5	1	0

Notes
[29] - Safety Population.
[30] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with any SAEs and common (>=2%) non-SAEs: Up to Week 148

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End point title

Number of participants with any SAEs and common (>=2%) non-SAEs: Up to Week 148

End point description

An AE is any untoward medical occurrence temporally associated with the use of a study treatment, whether or not considered related to study treatment. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other important medical event as per medical or scientific judgment. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen.

End point type

Secondary

End point timeframe

Up to Week 148

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[31]	371 ^[32]
Units: Participants
Any non-SAE (>=2%)	307	304
Any SAE	57	44

Notes
[31] - Safety Population.
[32] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with any SAEs and common (>=2%) non-SAEs: Up to Week 48

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End point title

Number of participants randomized to TBR arm receiving TDF-based regimen with any SAEs and common (>=2%) non-SAEs: Up to Week 48

End point description

An AE is any untoward medical occurrence temporally associated with the use of a study treatment, whether or not considered related to study treatment. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other important medical event as per medical or scientific judgment. Number of TDF-based regimen participants with any SAE and common (>=2%) non-SAEs are presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen.Data not collected post week48 as the participant withdrew from the study

End point type

Secondary

End point timeframe

Up to Week 48

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[33]
Units: Participants
Any non-SAE (>=2%)	1
Any SAE	0

Notes
[33] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with AEs by their severity Grades: Up to Week 48

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End point title

Number of participants randomized to TBR arm receiving TDF-based regimen with AEs by their severity Grades: Up to Week 48

End point description

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the DAIDS toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of TDF-based regimen participants with adverse events by maximum grade have been presented. Safety Population. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."Data not collected post week 48 as the participant withdrew from the study

End point type

Secondary

End point timeframe

Up to Week 48

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[34]
Units: Participants
Grade 1	0
Grade 2	1
Grade 3	0
Grade 4	0
Grade 5	0

Notes
[34] - Safety Population.

No statistical analyses for this end point

Secondary: Number of Participants With AEs by Their Severity Grades: Up to Week 144

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End point title

Number of Participants With AEs by Their Severity Grades: Up to Week 144

End point description

End point type

Secondary

End point timeframe

Up to Week 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[35]	371 ^[36]
Units: Participants
Grade 1	57	65
Grade 2	217	208
Grade 3	50	54
Grade 4	9	8
Grade 5	3	0

Notes
[35] - Safety Population
[36] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants who discontinued the treatment due to AEs: Up to Week 48

Top of page

End point title

Number of participants who discontinued the treatment due to AEs: Up to Week 48

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Number of participants who discontinued the treatment due to adverse events have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[37]	371 ^[38]
Units: Participants	13	2

Notes
[37] - Safety Population.
[38] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants who discontinued the treatment due to AEs: Up to Week 144

Top of page

End point title

Number of participants who discontinued the treatment due to AEs: Up to Week 144

End point description

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."

End point type

Secondary

End point timeframe

Up to Week 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[39]	371 ^[40]
Units: Participants	23	7

Notes
[39] - Safety Population.
[40] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with Maximum Post-Baseline emergent hematology toxicities: Up to Week 48

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End point title

Number of participants with Maximum Post-Baseline emergent hematology toxicities: Up to Week 48

End point description

Blood samples were collected up to Week 48 for the analysis of hematology parameters-platelet count, neutrophils, hemoglobin and leukocytes. Any abnormality in hematology parameters were evaluated according to the DAIDS toxicity scale from Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent hematology toxicities in any of the hematology parameters have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[41]	371 ^[42]
Units: Participants
Hemoglobin, Grade 1	3	0
Hemoglobin, Grade 2	0	0
Hemoglobin, Grade 3	0	0
Hemoglobin, Grade 4	0	0
Leukocytes, Grade 1	1	1
Leukocytes, Grade 2	1	0
Leukocytes, Grade 3	0	0
Leukocytes, Grade 4	0	0
Neutrophils, Grade 1	3	4
Neutrophils, Grade 2	2	4
Neutrophils, Grade 3	0	0
Neutrophils, Grade 4	1	0
Platelets, Grade 1	6	5
Platelets, Grade 2	1	1
Platelets, Grade 3	0	0
Platelets, Grade 4	0	0

Notes
[41] - Safety Population.
[42] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen who discontinued the treatment due to AEs: Up to Week 48

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End point title

Number of participants randomized to TBR arm receiving TDF-based regimen who discontinued the treatment due to AEs: Up to Week 48

End point description

End point type

Secondary

End point timeframe

Up to Week 48

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[43]
Units: Participants	0

Notes
[43] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with Maximum Post-Baseline emergent hematology toxicities: Up to Week 36

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End point title

Number of participants randomized to TBR arm receiving TDF-based regimen with Maximum Post-Baseline emergent hematology toxicities: Up to Week 36

End point description

Blood samples were collected up to the Week 36 visit for the analysis of hematology parameters-platelet count, neutrophils, hemoglobin and leukocytes. Any abnormality in hematology parameters were evaluated according to the DAIDS toxicity scale from Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms. Only those TDF-based regimen participants with maximum post-Baseline emergent hematology toxicities in any of the hematology parameters have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."Data not collected post week 36 as the participant withdrew from the study

End point type

Secondary

End point timeframe

Up to Week 36

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[44]
Units: Participants
Hemoglobin, Grade 1	0
Hemoglobin, Grade 2	0
Hemoglobin, Grade 3	0
Hemoglobin, Grade 4	0
Leukocytes, Grade 1	0
Leukocytes, Grade 2	0
Leukocytes, Grade 3	0
Leukocytes, Grade 4	0
Neutrophils, Grade 1	0
Neutrophils, Grade 2	0
Neutrophils, Grade 3	0
Neutrophils, Grade 4	0
Platelets, Grade 1	0
Platelets, Grade 2	0
Platelets, Grade 3	0
Platelets, Grade 4	0

Notes
[44] - Safety Population.

No statistical analyses for this end point

Secondary: Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities: Up to Week 144

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End point title

Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities: Up to Week 144

End point description

Blood samples were collected up to Week 144 for the analysis of hematology parameters-platelet count, neutrophils, hemoglobin and leukocytes. Any abnormality in hematology parameters are planned to be evaluated according to the DAIDS toxicity scale from Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."

End point type

Secondary

End point timeframe

Up to Week 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[45]	371 ^[46]
Units: Participants
Hemoglobin, Grade 1	7	2
Hemoglobin, Grade 2	1	2
Hemoglobin, Grade 3	0	0
Hemoglobin, Grade 4	0	0
Leukocytes, Grade 1	2	4
Leukocytes, Grade 2	1	0
Leukocytes, Grade 3	1	0
Leukocytes, Grade 4	0	0
Neutrophils, Grade 1	5	5
Neutrophils, Grade 2	3	8
Neutrophils, Grade 3	0	0
Neutrophils, Grade 4	2	2
Platelets, Grade 1	8	7
Platelets, Grade 2	2	1
Platelets, Grade 3	0	0
Platelets, Grade 4	0	0

Notes
[45] - Safety Population.
[46] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with Maximum Post-Baseline emergent clinical chemistry toxicities: Up to Week 48

Top of page

End point title

Number of participants with Maximum Post-Baseline emergent clinical chemistry toxicities: Up to Week 48

End point description

Blood samples were collected for analysis of alanine aminotransferase(ALT), albumin, alkaline phosphate(ALP), aspartate aminotransferase(AST), bilirubin, carbon dioxide(CO2), cholesterol, creatinine kinase(CK), creatinine, direct bilirubin, glomerular filtration rate(GFR) from creatinine adjusted for body surface area(BSA), GFR from cystatin C adjusted using chronic kidney disease-epidemiology collaboration(CKD-EPI), hyper/hypocalcemia, hyper/hypo-glycemia, hyper/hypo-kalemia, hyper/hypo-natremia, low density lipoprotein(LDL) cholesterol, phosphate and triglycerides. Any abnormality was evaluated according to DAIDS toxicity scale From Grade1-4 as mild,moderates,severe and Potentially life-threatening. Higher the grade, more severe the symptoms. 1 participant randomized to TBR but received TDF and because safety profiles of TDF and TAF differ, this participant was removed from overall safety population and presented in separate arm "Randomized to TBR but received TDF-based regimen."

End point type

Secondary

End point timeframe

Up to Week 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[47]	371 ^[48]
Units: Participants
ALT, Grade 1	24	18
ALT, Grade 2	6	4
ALT, Grade 3	1	1
ALT, Grade 4	0	0
Albumin, Grade 1	1	0
Albumin, Grade 2	0	0
Albumin, Grade 3	0	0
Albumin, Grade 4	0	0
ALP, Grade 1	2	0
ALP, Grade 2	0	0
ALP, Grade 3	0	0
ALP, Grade 4	0	0
AST, Grade 1	21	29
AST, Grade 2	7	4
AST, Grade 3	1	0
AST, Grade 4	1	0
Bilirubin, Grade 1	17	7
Bilirubin, Grade 2	5	2
Bilirubin, Grade 3	1	1
Bilirubin, Grade 4	0	0
CO2, Grade 1	73	70
CO2, Grade 2	1	1
CO2, Grade 3	0	0
CO2, Grade 4	0	0
Cholesterol, Grade 1	27	52
Cholesterol, Grade 2	12	19
Cholesterol, Grade 3	1	0
Cholesterol, Grade 4	0	0
CK, Grade 1	28	19
CK, Grade 2	4	9
CK, Grade 3	9	8
CK, Grade 4	6	5
Creatinine, Grade 1	16	7
Creatinine, Grade 2	3	1
Creatinine, Grade 3	0	0
Creatinine, Grade 4	0	0
Direct bilirubin, Grade 1	0	0
Direct bilirubin, Grade 2	0	0
Direct bilirubin, Grade 3	8	1
Direct bilirubin, Grade 4	0	0
GFR from creatinine adjusted using CKD EPI,Grade 1	0	0
GFR from creatinine adjusted using CKD EPI,Grade 2	135	83
GFR from creatinine adjusted using CKD EPI,Grade 3	26	13
GFR from creatinine adjusted using CKD EPI,Grade 4	0	0
GFR from cystatin C adjusted using CKD-EPI,Grade 1	0	0
GFR from cystatin C adjusted using CKD-EPI,Grade 2	52	66
GFR from cystatin C adjusted using CKD-EPI,Grade 3	5	4
GFR from cystatin C adjusted using CKD-EPI,Grade 4	1	0
Hypercalcemia, Grade 1	7	3
Hypercalcemia, Grade 2	0	0
Hypercalcemia, Grade 3	0	0
Hypercalcemia, Grade 4	0	0
Hyperglycemia, Grade 1	56	64
Hyperglycemia, Grade 2	21	19
Hyperglycemia, Grade 3	2	2
Hyperglycemia, Grade 4	0	0
Hyperkalemia, Grade 1	0	2
Hyperkalemia, Grade 2	2	0
Hyperkalemia, Grade 3	0	0
Hyperkalemia, Grade 4	0	0
Hypernatremia, Grade 1	1	1
Hypernatremia, Grade 2	0	0
Hypernatremia, Grade 3	0	0
Hypernatremia, Grade 4	0	0
Hypocalcemia, Grade 1	8	1
Hypocalcemia, Grade 2	0	1
Hypocalcemia, Grade 3	0	0
Hypocalcemia, Grade 4	0	0
Hypoglycemia, Grade 1	5	6
Hypoglycemia, Grade 2	3	2
Hypoglycemia, Grade 3	0	0
Hypoglycemia, Grade 4	0	0
Hypokalemia, Grade 1	7	1
Hypokalemia, Grade 2	1	0
Hypokalemia, Grade 3	0	0
Hypokalemia, Grade 4	0	0
Hyponatremia, Grade 1	8	13
Hyponatremia, Grade 2	0	2
Hyponatremia, Grade 3	0	0
Hyponatremia, Grade 4	0	0
LDL cholesterol, Grade 1	28	35
LDL cholesterol, Grade 2	13	15
LDL cholesterol, Grade 3	6	3
LDL cholesterol, Grade 4	0	0
Phosphate, Grade 1	38	47
Phosphate, Grade 2	2	7
Phosphate, Grade 3	0	0
Phosphate, Grade 4	0	0
Triglycerides, Grade 1	34	48
Triglycerides, Grade 2	4	11
Triglycerides, Grade 3	4	4
Triglycerides, Grade 4	4	0

Notes
[47] - Safety Population.
[48] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with Maximum Post-Baseline emergent clinical chemistry toxicities: Up to Week 36

Top of page

End point title

Number of participants randomized to TBR arm receiving TDF-based regimen with Maximum Post-Baseline emergent clinical chemistry toxicities: Up to Week 36

End point description

Blood samples were collected up to Week 36 visit for analysis of clinical chemistry parameters:ALT, albumin,ALP,AST,bilirubin,CO2,cholesterol,CK,creatinine,direct bilirubin,GFR from creatinine adjusted for BSA, GFR from cystatin C adjusted using CKD-EPI, hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, LDL cholesterol, phosphate& triglycerides. Any abnormality in clinical chemistry parameters were evaluated according to DAIDS toxicity scale From Grade 1 to 4:Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe),Grade 4 (Potentially life-threatening). Higher the grade, more severe the symptoms. One participant randomized to TBR but received TDF-based regimen & because safety profiles of TDF&TAF differ, this participant was removed from overall safety population & is presented in separate arm "Randomized to TBR but received TDF-based regimen." Data not collected post week 36 as the participant withdrew from the study.

End point type

Secondary

End point timeframe

Up to Week 36

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[49]
Units: Participants
ALT, Grade 1	0
ALT, Grade 2	0
ALT, Grade 3	0
ALT, Grade 4	0
Albumin, Grade 1	0
Albumin, Grade 2	0
Albumin, Grade 3	0
Albumin, Grade 4	0
ALP, Grade 1	0
ALP, Grade 2	0
ALP, Grade 3	0
ALP, Grade 4	0
AST, Grade 1	0
AST, Grade 2	0
AST, Grade 3	0
AST, Grade 4	0
Bilirubin, Grade 1	0
Bilirubin, Grade 2	0
Bilirubin, Grade 3	0
Bilirubin, Grade 4	0
CO2, Grade 1	0
CO2, Grade 2	0
CO2, Grade 3	0
CO2, Grade 4	0
Cholesterol, Grade 1	0
Cholesterol, Grade 2	0
Cholesterol, Grade 3	0
Cholesterol, Grade 4	0
CK, Grade 1	0
CK, Grade 2	0
CK, Grade 3	0
CK, Grade 4	0
Creatinine, Grade 1	0
Creatinine, Grade 2	0
Creatinine, Grade 3	0
Creatinine, Grade 4	0
Direct bilirubin, Grade 1	0
Direct bilirubin, Grade 2	0
Direct bilirubin, Grade 3	0
Direct bilirubin, Grade 4	0
GFR from creatinine adjusted using CKD EPI,Grade 1	0
GFR from creatinine adjusted using CKD EPI,Grade 2	0
GFR from creatinine adjusted using CKD EPI,Grade 3	0
GFR from creatinine adjusted using CKD EPI,Grade 4	0
GFR from cystatin C adjusted using CKD-EPI,Grade 1	0
GFR from cystatin C adjusted using CKD-EPI,Grade 2	0
GFR from cystatin C adjusted using CKD-EPI,Grade 3	0
GFR from cystatin C adjusted using CKD-EPI,Grade 4	0
Hypercalcemia, Grade 1	0
Hypercalcemia, Grade 2	0
Hypercalcemia, Grade 3	0
Hypercalcemia, Grade 4	0
Hyperglycemia, Grade 1	0
Hyperglycemia, Grade 2	0
Hyperglycemia, Grade 3	0
Hyperglycemia, Grade 4	0
Hyperkalemia, Grade 1	0
Hyperkalemia, Grade 2	0
Hyperkalemia, Grade 3	0
Hyperkalemia, Grade 4	0
Hypernatremia, Grade 1	0
Hypernatremia, Grade 2	0
Hypernatremia, Grade 3	0
Hypernatremia, Grade 4	0
Hypocalcemia, Grade 1	0
Hypocalcemia, Grade 2	0
Hypocalcemia, Grade 3	0
Hypocalcemia, Grade 4	0
Hypoglycemia, Grade 1	0
Hypoglycemia, Grade 2	0
Hypoglycemia, Grade 3	0
Hypoglycemia, Grade 4	0
Hypokalemia, Grade 1	0
Hypokalemia, Grade 2	0
Hypokalemia, Grade 3	0
Hypokalemia, Grade 4	0
Hyponatremia, Grade 1	0
Hyponatremia, Grade 2	0
Hyponatremia, Grade 3	0
Hyponatremia, Grade 4	0
LDL cholesterol, Grade 1	0
LDL cholesterol, Grade 2	0
LDL cholesterol, Grade 3	0
LDL cholesterol, Grade 4	0
Phosphate, Grade 1	0
Phosphate, Grade 2	0
Phosphate, Grade 3	0
Phosphate, Grade 4	0
Triglycerides, Grade 1	1
Triglycerides, Grade 2	0
Triglycerides, Grade 3	0
Triglycerides, Grade 4	0

Notes
[49] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with Maximum Post-Baseline emergent clinical chemistry toxicities: Up to Week 144

Top of page

End point title

Number of participants with Maximum Post-Baseline emergent clinical chemistry toxicities: Up to Week 144

End point description

Blood samples were collected up to Week 144 for the analysis of clinical chemistry parameters: ALT, albumin, ALP, AST, bilirubin, CO2, cholesterol, CK, creatinine, direct bilirubin, GFR from creatinine adjusted for BSA, GFR from cystatin C adjusted using CKD-EPI, hypercalcemia, hyperglycemia, hyperkalemia, hypernatremia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, LDL cholesterol, phosphate triglycerides and lactate dehydrogenase. Any abnormality in clinical chemistry parameters were evaluated according to the DAIDS toxicity scale From Grade 1 to 4: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening). The higher the grade, the more severe the symptoms.One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."

End point type

Secondary

End point timeframe

Up to Week 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[50]	371 ^[51]
Units: Participants
ALT, Grade 1	55	49
ALT, Grade 2	11	9
ALT, Grade 3	5	3
ALT, Grade 4	0	1
Albumin, Grade 1	1	0
Albumin, Grade 2	2	0
Albumin, Grade 3	0	0
Albumin, Grade 4	0	0
ALP, Grade 1	6	0
ALP, Grade 2	0	0
ALP, Grade 3	0	1
ALP, Grade 4	0	0
AST, Grade 1	34	45
AST, Grade 2	13	9
AST, Grade 3	3	0
AST, Grade 4	3	3
Bilirubin, Grade 1	24	12
Bilirubin, Grade 2	9	4
Bilirubin, Grade 3	3	1
Bilirubin, Grade 4	0	0
CO2, Grade 1	110	97
CO2, Grade 2	2	4
CO2, Grade 3	1	0
CO2, Grade 4	0	0
Cholesterol, Grade 1	42	70
Cholesterol, Grade 2	26	34
Cholesterol, Grade 3	1	2
Cholesterol, Grade 4	0	0
CK, Grade 1	41	30
CK, Grade 2	12	13
CK, Grade 3	12	12
CK, Grade 4	10	10
Creatinine, Grade 1	21	12
Creatinine, Grade 2	5	2
Creatinine, Grade 3	1	1
Creatinine, Grade 4	0	0
Direct bilirubin, Grade 1	0	0
Direct bilirubin, Grade 2	0	0
Direct bilirubin, Grade 3	13	3
Direct bilirubin, Grade 4	0	0
GFR from creatinine adjusted using CKD EPI,Grade 1	0	0
GFR from creatinine adjusted using CKD EPI,Grade 2	165	101
GFR from creatinine adjusted using CKD EPI,Grade 3	38	24
GFR from creatinine adjusted using CKD EPI,Grade 4	0	1
GFR from cystatin C adjusted using CKD-EPI,Grade 1	0	0
GFR from cystatin C adjusted using CKD-EPI,Grade 2	169	183
GFR from cystatin C adjusted using CKD-EPI,Grade 3	46	58
GFR from cystatin C adjusted using CKD-EPI,Grade 4	1	1
Hypercalcemia, Grade 1	8	9
Hypercalcemia, Grade 2	0	0
Hypercalcemia, Grade 3	0	0
Hypercalcemia, Grade 4	0	0
Hyperglycemia, Grade 1	73	77
Hyperglycemia, Grade 2	40	31
Hyperglycemia, Grade 3	4	4
Hyperglycemia, Grade 4	0	0
Hyperkalemia, Grade 1	3	2
Hyperkalemia, Grade 2	2	1
Hyperkalemia, Grade 3	0	0
Hyperkalemia, Grade 4	0	0
Hypernatremia, Grade 1	4	3
Hypernatremia, Grade 2	1	0
Hypernatremia, Grade 3	0	0
Hypernatremia, Grade 4	0	0
Hypocalcemia, Grade 1	14	5
Hypocalcemia, Grade 2	1	2
Hypocalcemia, Grade 3	0	0
Hypocalcemia, Grade 4	0	0
Hypoglycemia, Grade 1	9	10
Hypoglycemia, Grade 2	4	3
Hypoglycemia, Grade 3	0	0
Hypoglycemia, Grade 4	0	0
Hypokalemia, Grade 1	10	7
Hypokalemia, Grade 2	3	0
Hypokalemia, Grade 3	1	0
Hypokalemia, Grade 4	0	0
Hyponatremia, Grade 1	21	26
Hyponatremia, Grade 2	0	2
Hyponatremia, Grade 3	0	0
Hyponatremia, Grade 4	0	0
LDL cholesterol, Grade 1	41	56
LDL cholesterol, Grade 2	19	24
LDL cholesterol, Grade 3	8	9
LDL cholesterol, Grade 4	0	0
Phosphate, Grade 1	61	71
Phosphate, Grade 2	3	9
Phosphate, Grade 3	0	0
Phosphate, Grade 4	0	0
Triglycerides, Grade 1	60	77
Triglycerides, Grade 2	6	15
Triglycerides, Grade 3	6	5
Triglycerides, Grade 4	4	2
Lactate Dehydrogenase Grade 1	0	1
Lactate Dehydrogenase Grade 2	0	0
Lactate Dehydrogenase Grade 3	0	0
Lactate Dehydrogenase Grade 4	0	0

Notes
[50] - Safety Population.
[51] - Safety Population.

No statistical analyses for this end point

Secondary: Change from Baseline in renal biomarkers- Urine albumin/creatinine (UA/C) ratio and Urine protein/creatinine (UP/C) ratio at Weeks 24 and 48

Top of page

End point title

Change from Baseline in renal biomarkers- Urine albumin/creatinine (UA/C) ratio and Urine protein/creatinine (UP/C) ratio at Weeks 24 and 48

End point description

Baseline is defined as Day 1. Change from Baseline in UA/C was calculated as UA/C ratio at post-Baseline visit minus UA/C ratio calculated at Baseline. Change from Baseline in UP/C and UA/C was calculated as UP/C and UA/C ratio at post-Baseline visit minus UP/C and UA/C ratio calculated at Baseline, respectively. Estimated geometric mean adjusted ratio and 95% CI have been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen. Total of 741 participants were analyzed but 740 participants are presented in this Outcome Measure and 1 participant is presented separately in next Outcome Measure. Participants with data available at specified data points were analyzed (represented by n= X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[52]	371 ^[53]
Units: Ratio
geometric mean (confidence interval 95%)
UA/C, Week 24, n=235, 230	1.080 (1.007 to 1.158)	1.022 (0.956 to 1.091)
UA/C, Week 48, n=230, 224	1.125 (1.036 to 1.222)	1.059 (0.963 to 1.165)
UP/C, Week 24, n=267, 261	0.955 (0.917 to 0.995)	0.976 (0.937 to 1.016)
UP/C, Week 48, n=261, 257	0.971 (0.926 to 1.018)	1.016 (0.964 to 1.070)

Notes
[52] - Safety Population.
[53] - Safety Population.

Statistical Analysis 1

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for UA/C at Week 24 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

= 0.257

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

1.057

Confidence interval

level

95%

sides

2-sided

lower limit

0.96

upper limit

1.164

Statistical Analysis 2

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for UA/C at Week 48 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

= 0.35

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

1.062

Confidence interval

level

95%

sides

2-sided

lower limit

0.936

upper limit

1.205

Statistical Analysis 3

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for UP/C at Week 24 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

= 0.473

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

0.979

Confidence interval

level

95%

sides

2-sided

lower limit

0.924

upper limit

1.037

Statistical Analysis 4

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for UP/C at Week 48 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

= 0.212

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

0.956

Confidence interval

level

95%

sides

2-sided

lower limit

0.891

upper limit

1.026

Secondary: Change from Baseline in renal biomarkers- UA/C ratio and UP/C ratio at Weeks 24 and 48 in participants randomized to TBR receiving TDF-based regimen

Top of page

End point title

Change from Baseline in renal biomarkers- UA/C ratio and UP/C ratio at Weeks 24 and 48 in participants randomized to TBR receiving TDF-based regimen

End point description

Urine samples were collected at Baseline, Week 24 and Week 48 to assess renal biomarkers - urine albumin/creatinine ratio and urine protein/creatinine ratio. Baseline was defined as the latest pre-dose assessment value (Day 1) with a non-missing value. Change from Baseline in UP/C and UA/C was calculated as UP/C and UA/C ratio at post-Baseline visit minus UP/C and UA/C ratio calculated at Baseline, respectively. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). 99999 indicates data is not available. Data not collected post week 48 as the participant withdrew from the study

End point type

Secondary

End point timeframe

Baseline (Day 1) and at weeks 24 and 48

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[54]
Units: Ratio
number (not applicable)
UA/C, Week 24, n=1	0
UA/C, Week 48, n=0	99999
UP/C, Week 24, n=1	0.3
UP/C, Week 48, n=0	99999

Notes
[54] - Safety Population.

No statistical analyses for this end point

Secondary: Change from Baseline in renal biomarkers- UA/C ratio and UP/C ratio at Weeks 96 and 144

Top of page

End point title

Change from Baseline in renal biomarkers- UA/C ratio and UP/C ratio at Weeks 96 and 144

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[55]	371 ^[56]
Units: Ratio
geometric mean (confidence interval 95%)
UA/C, Week 96, n=208, 175	1.058 (0.974 to 1.149)	1.075 (0.968 to 1.195)
UA/C, Week 144, n=202, 179	1.203 (1.093 to 1.324)	1.200 (1.051 to 1.371)
UP/C, Week 96, n=245, 206	1.048 (0.997 to 1.102)	1.105 (1.044 to 1.169)
UP/C, Week 144, n=237, 220	1.182 (1.121 to 1.247)	1.188 (1.104 to 1.278)

Notes
[55] - Safety Population.
[56] - Safety Population.

Statistical Analysis 1

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for UA/C at Week 96 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

= 0.7

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

0.977

Confidence interval

level

95%

sides

2-sided

lower limit

0.866

upper limit

1.102

Statistical Analysis 4

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for UP/C at Week 96 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

= 0.814

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

0.991

Confidence interval

level

95%

sides

2-sided

lower limit

0.916

upper limit

1.071

Statistical Analysis 3

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for UP/C at Week 96 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

= 0.356

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

0.969

Confidence interval

level

95%

sides

2-sided

lower limit

0.907

upper limit

1.036

Statistical Analysis 2

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for UA/C at Week 144 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

= 0.7

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

0.971

Confidence interval

level

95%

sides

2-sided

lower limit

0.835

upper limit

1.129

Secondary: Change from Baseline in renal biomarkers- Urine beta-2 microglobulin/urine creatinine ratio at Weeks 24 and 48

Top of page

End point title

Change from Baseline in renal biomarkers- Urine beta-2 microglobulin/urine creatinine ratio at Weeks 24 and 48

End point description

Geometric mean ratio (visit/Baseline) and 95% CI of geometric mean ratio has been presented. Baseline was defined as Day 1. Change from Baseline in urine beta-2-microglobulin/urine creatinine was calculated as urine beta-2-microglobulin/urine creatinine ratio at post-Baseline visit minus urine beta-2-microglobulin/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Total of 741 participants were analyzed but 740 participants are presented in this Outcome Measure and 1 participant is presented separately in next Outcome Measure. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[57]	371 ^[58]
Units: Ratio
geometric mean (confidence interval 95%)
Week 24, n=136, 141	0.991 (0.899 to 1.093)	1.034 (0.931 to 1.149)
Week 48, n=126, 141	0.973 (0.870 to 1.088)	0.922 (0.832 to 1.022)

Notes
[57] - Safety Population.
[58] - Safety Population.

Statistical Analysis 2

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine beta-2 microglobulin/urine creatinine at Week 48 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.489

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

1.055

Confidence interval

level

95%

sides

2-sided

lower limit

0.906

upper limit

1.229

Statistical Analysis 1

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine beta-2 microglobulin/urine creatinine at Week 24 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.56

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

0.958

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.106

Secondary: Change from Baseline in renal biomarkers- Urine phosphate at Weeks 24 and 48

Top of page

End point title

Change from Baseline in renal biomarkers- Urine phosphate at Weeks 24 and 48

End point description

Urine biomarker samples were collected at Baseline and at Weeks 24 and 48 to assess urine phosphate. Geometric mean ratio (visit divided by Baseline) and 95% CI of geometric mean ratio has been presented. Baseline was defined as Day 1. Change from Baseline in urine phosphate was calculated as urine phosphate at post-Baseline visit minus urine phosphate calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."Total of 741 participants were analyzed but 740 participants are presented in this Outcome Measure and 1 participant is presented separately in next Outcome Measure. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[59]	371 ^[60]
Units: Ratio
geometric mean (confidence interval 95%)
Week 24, n=348, 352	0.955 (0.888 to 1.028)	0.940 (0.871 to 1.014)
Week 48, n=342, 340	0.969 (0.892 to 1.052)	0.970 (0.900 to 1.044)

Notes
[59] - Safety Population.
[60] - Safety Population.

Statistical Analysis 2

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine phosphate at Week 48 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.985

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

0.999

Confidence interval

level

95%

sides

2-sided

lower limit

0.894

upper limit

1.116

Statistical Analysis 1

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine phosphate at Week 24 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.758

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

1.017

Confidence interval

level

95%

sides

2-sided

lower limit

0.915

upper limit

1.13

Secondary: Change from Baseline in renal biomarkers- Urine beta-2 microglobulin/urine creatinine ratio at Weeks 96 and 144

Top of page

End point title

Change from Baseline in renal biomarkers- Urine beta-2 microglobulin/urine creatinine ratio at Weeks 96 and 144

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[61]	371 ^[62]
Units: Ratio
geometric mean (confidence interval 95%)
Week 96, n=109, 107	1.080 (0.931 to 1.253)	0.986 (0.844 to 1.152)
Week 144, n=101, 97	0.904 (0.768 to 1.065)	0.958 (0.808 to 1.136)

Notes
[61] - Safety Population.
[62] - Safety Population.

Statistical Analysis 2

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine beta-2 microglobulin/urine creatinine at Week 144 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.834

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

0.981

Confidence interval

level

95%

sides

2-sided

lower limit

0.819

upper limit

1.175

Statistical Analysis 1

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine beta-2 microglobulin/urine creatinine at Week 96 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.081

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

1.165

Confidence interval

level

95%

sides

2-sided

lower limit

0.981

upper limit

1.384

Secondary: Change from Baseline in renal biomarkers- Urine phosphate at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

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End point title

Change from Baseline in renal biomarkers- Urine phosphate at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

End point description

Urine biomarker samples were collected to assess urine phosphate. Baseline (Day 1) value was the value from the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in urine phosphate was calculated as urine phosphate at post-Baseline visit minus urine phosphate calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."99999 indicates data is not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data not collected post week 48 as the participant withdrew from the study.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at weeks 24 and 48

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[63]
Units: Ratio
number (not applicable)
Week 24, n=1	2.9
Week 48, n=0	99999

Notes
[63] - Safety Population.

No statistical analyses for this end point

Secondary: Change from Baseline in renal biomarkers- Urine phosphate at Weeks 96 and 144

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End point title

Change from Baseline in renal biomarkers- Urine phosphate at Weeks 96 and 144

End point description

Urine biomarker samples were collected at Baseline, Weeks 96 and 144 to assess urine phosphate. Geometric mean ratio (visit divided by Baseline) and 95% CI of geometric mean ratio has been presented. Baseline was defined as Day 1. Change from Baseline in urine phosphate was calculated as urine phosphate at post-Baseline visit minus urine phosphate calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Total of 741 participants were analyzed but 740 participants are presented in this Outcome Measure and 1 participant is presented separately in next Outcome Measure. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[64]	371 ^[65]
Units: Ratio
geometric mean (confidence interval 95%)
Week 96, n=312, 286	0.960 (0.871 to 1.057)	0.978 (0.882 to 1.085)
Week 144, n=313, 298	0.890 (0.805 to 0.985)	0.912 (0.825 to 1.007)

Notes
[64] - Safety Population.
[65] - Safety Population.

Statistical Analysis 2

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine phosphate at Week 144 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.745

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

1.019

Confidence interval

level

95%

sides

2-sided

lower limit

0.909

upper limit

1.142

Statistical Analysis 1

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine phosphate at Week 96 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.806

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

1.015

Confidence interval

level

95%

sides

2-sided

lower limit

0.904

upper limit

1.139

Secondary: Change from Baseline in renal biomarkers- Urine retinol binding protein 4/urine creatinine at weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

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End point title

Change from Baseline in renal biomarkers- Urine retinol binding protein 4/urine creatinine at weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

End point description

Urine biomarker samples were collected to assess urine retinol binding protein 4/urine creatinine.Baseline (Day 1) value was the value from the latest pre-dose assessment with non-missing value, including those from unscheduled visits.Change from Baseline in urine retinol binding protein 4/urine creatinine was calculated as urine retinol binding protein 4/urine creatinine ratio at post-Baseline visit minus urine retinol binding protein 4/urine creatinine ratio calculated at Baseline.One participant randomized to TBR but received TDF-based regimen & because the safety profiles of TDF & TAF differ, participant was removed from the overall safety population & is presented in separate arm "Randomized to TBR but received TDF-based regimen." 99999 indicates data is not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data not collected post week48 as the participant withdrew from the study.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at weeks 24 and 48

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[66]
Units: Ratio
number (not applicable)
Week 24, n=1	1.04
Week 48, n=0	99999

Notes
[66] - Safety Population.

No statistical analyses for this end point

Secondary: Change from Baseline in renal biomarkers- Urine retinol binding protein 4/urine creatinine at Weeks 24 and 48

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End point title

Change from Baseline in renal biomarkers- Urine retinol binding protein 4/urine creatinine at Weeks 24 and 48

End point description

Geometric mean ratio (visit/Baseline) and 95% CI of geometric mean ratio has been presented. Baseline is defined as Day 1. Change from Baseline in Urine retinol binding protein 4/urine creatinine ratio was calculated as Urine retinol binding protein 4/urine creatinine ratio at post-Baseline visit minus Urine retinol binding protein 4/urine creatinine ratio calculated at Baseline. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Total of 741 participants were analyzed but 740 participants are presented in this Outcome Measure and 1 participant is presented separately in next Outcome Measure. Only those participants with data available at specified data points were analyzed (represented by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[67]	371 ^[68]
Units: Ratio
geometric mean (confidence interval 95%)
Week 24, n=344, 343	0.860 (0.790 to 0.936)	0.920 (0.847 to 0.999)
Week 48, n=340, 335	1.063 (0.992 to 1.139)	1.068 (0.996 to 1.144)

Notes
[67] - Safety Population.
[68] - Safety Population.

Statistical Analysis 2

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine retinol binding protein 4/urine creatinine at Week 48 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.932

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

0.996

Confidence interval

level

95%

sides

2-sided

lower limit

0.903

upper limit

1.098

Statistical Analysis 1

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine retinol binding protein 4/urine creatinine at Week 24 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.264

Method

Mixed Model Reported Measures

Parameter type

Treatment ratio

Point estimate

0.935

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.052

Secondary: Change from Baseline in renal biomarkers- Urine retinol binding protein 4/urine creatinine at Weeks 96 and 144

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End point title

Change from Baseline in renal biomarkers- Urine retinol binding protein 4/urine creatinine at Weeks 96 and 144

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[69]	371 ^[70]
Units: Ratio
geometric mean (confidence interval 95%)
Week 96, n=310, 282	0.926 (0.845 to 1.014)	0.851 (0.775 to 0.933)
Week 144, n=304, 288	1.188 (1.086 to 1.298)	1.227 (1.109 to 1.359)

Notes
[69] - Safety Population.
[70] - Safety Population.

Statistical Analysis 2

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine retinol binding protein 4/urine creatinine at Week 144 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.895

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

1.007

Confidence interval

level

95%

sides

2-sided

lower limit

0.905

upper limit

1.121

Statistical Analysis 1

Statistical analysis description

Treatment ratio (DTG+3TC/ TAF based regimen) and 95% CI for Urine retinol binding protein 4/urine creatinine at Week 96 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.011

Method

Mixed Model Repeated Measures

Parameter type

Treatment ratio

Point estimate

1.15

Confidence interval

level

95%

sides

2-sided

lower limit

1.032

upper limit

1.281

Secondary: Change from Baseline in fasting lipids at Weeks 24 and 48

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End point title

Change from Baseline in fasting lipids at Weeks 24 and 48

End point description

Blood samples were collected at Baseline (Day 1), Week 24 and Week 48 to assess fasting lipids which included plasma cholesterol, plasma LDL cholesterol, plasma high density lipoprotein (HDL) cholesterol and plasma triglycerides. Baseline value was the value from the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Safety Population. Total of 741 participants were analyzed but 740 participants are presented in this Outcome Measure and 1 participant is presented separately in next Outcome Measure. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[71]	371 ^[72]
Units: Millimoles per liter
median (inter-quartile range (Q1-Q3))
Plasma cholesterol, Week 24, n=282, 264	-0.325 (-0.750 to 0.150)	0.000 (-0.400 to 0.400)
Plasma cholesterol, Week 48, n=275, 263	-0.200 (-0.750 to 0.150)	0.100 (-0.350 to 0.500)
Plasma LDL Cholesterol, Week 24, n=282, 264	-0.210 (-0.570 to 0.130)	-0.060 (-0.340 to 0.410)
Plasma LDL Cholesterol, Week 48, n=275, 263	-0.170 (-0.560 to 0.210)	0.070 (-0.320 to 0.430)
Plasma Triglycerides, Week 24, n=282, 264	-0.100 (-0.460 to 0.160)	0.060 (-0.200 to 0.350)
Plasma Triglycerides, Week 48, n=275, 263	-0.100 (-0.440 to 0.160)	0.100 (-0.280 to 0.380)
Plasma HDL Cholesterol, Week 24, n=282, 264	-0.050 (-0.150 to 0.100)	0.050 (-0.150 to 0.150)
Plasma HDL Cholesterol, Week 48, n=275, 263	0.000 (-0.200 to 0.150)	0.050 (-0.150 to 0.150)

Notes
[71] - Safety Population.
[72] - Safety Population.

No statistical analyses for this end point

Secondary: Change from Baseline in fasting lipids at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

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End point title

Change from Baseline in fasting lipids at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

End point description

Blood samples were collected (participant withdrew from the study at Week 36) to assess fasting lipids which included plasma cholesterol, plasma LDL cholesterol, plasma HDL cholesterol & plasma triglycerides. Baseline value was the value from latest pre-dose assessment with non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline values for fasting lipids in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen & because the safety profiles of TDF & TAF differ,participant was removed from the overall safety population & is presented in separate arm "Randomized to TBR but received TDF-based regimen." 99999 indicates data is not available.Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data not collected post week48 as the participant withdrew from the study.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at weeks 24 and 48

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[73]
Units: Millimoles per liter
number (not applicable)
Plasma cholesterol, Week 24, n=1	0
Plasma cholesterol, Week 48, n=0	99999
Plasma LDL Cholesterol, Week 24, n=1	-0.67
Plasma LDL Cholesterol, Week 48, n=0	99999
Plasma Triglycerides, Week 24, n=1	1.36
Plasma Triglycerides, Week 48, n=0	99999
Plasma HDL Cholesterol, Week 24, n=1	0.05
Plasma HDL Cholesterol, Week 48, n=0	99999

Notes
[73] - Safety Population.

No statistical analyses for this end point

Secondary: Change from Baseline in fasting lipids at Weeks 96 and 144

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End point title

Change from Baseline in fasting lipids at Weeks 96 and 144

End point description

Blood samples were collected at Baseline (Day 1), Weeks 96 and 144 to assess fasting lipids which included plasma cholesterol, plasma LDL cholesterol, plasma high density lipoprotein (HDL) cholesterol and plasma triglycerides. Baseline value was the value from the latest pre-dose assessment (Day 1) with a non-missing value. Change from Baseline is defined as post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Total of 741 participants were analyzed but 740 participants are presented in this Outcome Measure and 1 participant is presented separately in next Outcome Measure. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[74]	371 ^[75]
Units: Millimoles per liter
median (inter-quartile range (Q1-Q3))
Plasma cholesterol, Week 96, n=238, 213	-3.7 (-12.4 to 5.6)	1.2 (-6.0 to 10.6)
Plasma cholesterol, Week 144, n=243, 230	-4.0 (-13.0 to 6.4)	3.8 (-5.0 to 14.5)
Plasma LDL Cholesterol, Week 96, n=238, 213	-5.6 (-17.3 to 10.8)	1.7 (-8.9 to 15.8)
Plasma LDL Cholesterol, Week 144, n=243, 230	-5.0 (-16.2 to 10.7)	4.2 (-9.0 to 20.9)
Plasma Triglycerides, Week 96, n=238, 213	-2.1 (-25.8 to 22.2)	4.9 (-20.0 to 38.9)
Plasma Triglycerides, Week 144, n=243, 230	-9.4 (-32.8 to 21.2)	2.2 (-23.0 to 30.3)
Plasma HDL Cholesterol, Week 96, n=238, 213	-3.8 (-13.8 to 8.5)	0.0 (-10.8 to 13.0)
Plasma HDL Cholesterol, Week 144, n=243, 230	-3.8 (-14.3 to 12.0)	3.8 (-8.0 to 17.4)

Notes
[74] - Safety Population.
[75] - Safety Population.

No statistical analyses for this end point

Secondary: Number of participants with genotypic resistance: Up to Week 48

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End point title

Number of participants with genotypic resistance: Up to Week 48

End point description

Plasma samples were collected for drug resistance testing. Number of participants, who met confirmed virologic withdrawal (CVW) criteria (one plasma HIV-1 RNA >=200 c/mL after Day 1 with immediate prior HIV RNA >=50 c/mL), with emergent genotypic resistance to INSTI, nucleoside reverse transcriptase inhibitor (NRTI), NNRTI and PI was summarized. CVW Population comprises all participants in the ITT-E Population who had met the derived CVW criteria. One participant randomized to TBR but received TDF-based regimen and was presented within the "TBR (TAF-based regimen) arm" as efficacy of TAF and TDF are comparable.

End point type

Secondary

End point timeframe

Up to Week 48

End point values	TAF Based Regimen (Early switch)
Number of subjects analysed	1 ^[76]
Units: Participants
INSTI	0
NRTI	0
NNRTI	0
PI	0

Notes
[76] - CVW Population.

No statistical analyses for this end point

Secondary: Number of participants with genotypic resistance: Up to Week 144

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End point title

Number of participants with genotypic resistance: Up to Week 144

End point description

Plasma samples were collected for drug resistance testing. Number of participants, who meet CVW criteria (one plasma HIV-1 RNA >=200 c/mL after Day 1 with immediate prior HIV RNA >=50 c/mL), with genotypic resistance to INSTI, NRTI, NNRTI and PI are summarized. CVW Population comprises all participants in the ITT-E Population who had met the derived CVW criteria and who had resistance data. One participant randomized to TBR but received TDF-based regimen and was presented within the "TBR (TAF-based regimen) arm" as efficacy of TAF and TDF are comparable.

End point type

Secondary

End point timeframe

Up to Week 144

End point values	TAF Based Regimen (Early Switch)
Number of subjects analysed	2 ^[77]
Units: Participants
INSTI	0
NRTI	0
NNRTI	0
PI	0

Notes
[77] - CVW Population

No statistical analyses for this end point

Secondary: Number of participants with phenotypic resistance: Up to Week 48

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End point title

Number of participants with phenotypic resistance: Up to Week 48

End point description

Number of participants, who meet CVW criteria (one plasma HIV-1 RNA >=200 c/mL after Day 1 with immediate prior HIV RNA >=50 c/mL), with phenotypic resistance to INSTI, NNRTI,NRTI and PI were summarized. Assessment of antiviral activity of ART using phenotypic test results was interpreted through a proprietary algorithm (from Monogram Biosciences), which provided the overall susceptibility of the drug. Partially sensitive and resistant calls were considered resistant in this analysis. The phenotypic resistance was calculated using binary scoring system, where 0 was considered as sensitive and 1 as resistance. Phenotypic Resistance data for the following INSTI, NNRTI, NRTI and PI drugs in participants Meeting CVW Criteria has been presented. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable.

End point type

Secondary

End point timeframe

Up to Week 48

End point values	TAF Based Regimen (Early switch)
Number of subjects analysed	1 ^[78]
Units: Participants
INSTI, DTG, Sensitive	1
INSTI, DTG, Resistant	0
INSTI, Bictegravir (BIC), Sensitive	1
INSTI, BIC, Resistant	0
INSTI, Elvitegravir (EVG), Sensitive	1
INSTI, EVG, Resistant	0
INSTI, Raltegravir (RAL), Sensitive	1
INSTI, RAL, Resistant	0
NNRTI, Delavirdine (DLV), Sensitive	1
NNRTI, DLV, Resistant	0
NNRTI, Efavirenz (EFV), Sensitive	1
NNRTI, EFV, Resistant	0
NNRTI, Etravirine (ETR), Sensitive	1
NNRTI, ETR, Resistant	0
NNRTI, Nevirapine (NVP), Sensitive	1
NNRTI, NVP, Resistant	0
NNRTI, Rilpivirine (RPV), Sensitive	1
NNRTI, RPV, Resistant	0
NRTI, 3TC, Sensitive	1
NRTI, 3TC, Resistant	0
NRTI, Abacavir (ABC), Sensitive	1
NRTI, ABC, Resistant	0
NRTI, Zidovudine (AZT), Sensitive	1
NRTI, AZT, Resistant	0
NRTI, Stavudine (D4T), Sensitive	1
NRTI, D4T, Resistant	0
NRTI, Didanosine (DDI), Sensitive	1
NRTI, DDI, Resistant	0
NRTI, Emtricitabine (FTC), Sensitive	1
NRTI, FTC, Resistant	0
NRTI, Tenofovir (TDF), Sensitive	1
NRTI, TDF, Resistant	0
PI, Atazanavir (ATV), Sensitive	1
PI, ATV, Resistant	0
PI, Darunavir (DRV), Sensitive	1
PI, DRV, Resistant	0
PI, Fosamprenavir (FPV), Sensitive	1
PI, FPV, Resistant	0
PI, Indinavir (IDV), Sensitive	1
PI, IDV, Resistant	0
PI, Lopinavir (LPV), Sensitive	1
PI, LPV, Resistant	0
PI, Nelfinavir (NFV), Sensitive	1
PI, NFV, Resistant	0
PI, Ritonavir (RTV), Sensitive	1
PI, RTV, Resistant	0
PI, Saquinavir (SQV), Sensitive	1
PI, SQV, Resistant	0
PI, Tipranavir (TPV), Sensitive	1
PI, TPV, Resistant	0

Notes
[78] - CVW Population.

No statistical analyses for this end point

Secondary: Number of Participants With Phenotypic Resistance: Up to Week 144

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End point title

Number of Participants With Phenotypic Resistance: Up to Week 144

End point description

Number of participants, who meet CVW criteria (one plasma HIV-1 RNA >=200 c/mL after Day 1 with immediate prior HIV RNA >=50 c/mL), with phenotypic resistance to INSTI,NNRT,NRTI and PIwere summarized. Assessment of antiviral activity of anti-retroviral therapy (ART) using phenotypic test results was interpreted through a proprietary algorithm (from Monogram Biosciences), which provided the overall susceptibility of the drug. Partially sensitive and resistant calls were considered resistant in this analysis. The phenotypic resistance was calculated using binary scoring system, where 0 was considered as sensitive and 1 as resistance. Phenotypic Resistance data for the following INSTI, NNRTI, NRTI and PI drugs in participants Meeting CVW Criteria has been presented. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable.

End point type

Secondary

End point timeframe

Up to Week 144

End point values	TAF Based Regimen (Early Switch)
Number of subjects analysed	2 ^[79]
Units: Participants
INSTI, DTG, Sensitive	2
INSTI, DTG, Resistant	0
INSTI, Bictegravir (BIC), Sensitive	2
INSTI, BIC, Resistant	0
INSTI, Elvitegravir (EVG), Sensitive	2
INSTI, EVG, Resistant	0
INSTI, Raltegravir (RAL), Sensitive	2
INSTI, RAL, Resistant	0
NNRTI, Delavirdine (DLV), Sensitive	2
NNRTI, DLV, Resistant	0
NNRTI, Efavirenz (EFV), Sensitive	2
NNRTI, EFV, Resistant	0
NNRTI, Etravirine (ETR), Sensitive	2
NNRTI, ETR, Resistant	0
NNRTI, Nevirapine (NVP), Sensitive	2
NNRTI, NVP, Resistant	0
NNRTI, Rilpivirine (RPV), Sensitive	2
NNRTI, RPV, Resistant	0
NRTI, 3TC, Sensitive	2
NRTI, 3TC, Resistant	0
NRTI, Abacavir (ABC), Sensitive	2
NRTI, ABC, Resistant	0
NRTI, Zidovudine (AZT), Sensitive	2
NRTI, AZT, Resistant	0
NRTI, Stavudine (D4T), Sensitive	2
NRTI, D4T, Resistant	0
NRTI, Didanosine (DDI), Sensitive	2
NRTI, DDI, Resistant	0
NRTI, Emtricitabine (FTC), Sensitive	2
NRTI, FTC, Resistant	0
NRTI, Tenofovir (TDF), Sensitive	2
NRTI, TDF, Resistant	0
PI, Atazanavir (ATV), Sensitive	2
PI, ATV, Resistant	0
PI, Darunavir (DRV), Sensitive	2
PI, DRV, Resistant	0
PI, Fosamprenavir (FPV), Sensitive	2
PI, FPV, Resistant	0
PI, Indinavir (IDV), Sensitive	2
PI, IDV, Resistant	0
PI, Lopinavir (LPV), Sensitive	2
PI, LPV, Resistant	0
PI, Nelfinavir (NFV), Sensitive	2
PI, NFV, Resistant	0
PI, Ritonavir (RTV), Sensitive	2
PI, RTV, Resistant	0
PI, Saquinavir (SQV), Sensitive	2
PI, SQV, Resistant	0
PI, Tipranavir (TPV), Sensitive	2
PI, TPV, Resistant	0

Notes
[79] - CVW Population

No statistical analyses for this end point

Secondary: Change from Baseline in bone biomarkers-serum bone-specific ALP (Bone-ALP), osteocalcin, serum procollagen 1 N-Terminal propeptide (P1NP) and serum type 1 collagen C-telopeptides (CTX-1) at Weeks 24 and 48

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End point title

Change from Baseline in bone biomarkers-serum bone-specific ALP (Bone-ALP), osteocalcin, serum procollagen 1 N-Terminal propeptide (P1NP) and serum type 1 collagen C-telopeptides (CTX-1) at Weeks 24 and 48

End point description

Baseline was (Day 1).Change from Baseline is post-dose visit value - Baseline value.Adjusted mean was estimated mean change from Baseline at each visit calculated from a repeated measures model adjusting for treatment, visit,Baseline third agent class, CD4+ cell count(continuous),age(continuous),sex,race,body mass index(BMI,continuous),smoking status, vitaminD use, Baseline biomarker(continuous),treatment by visit interaction,& Baseline value by visit interaction,with visit as repeated factor.1 participant randomized to TBR but received TDF & because safety profiles of TDF & TAF differ, participant was removed from overall safety population & presented in separate arm"Randomized to TBR but received TDF-based regimen''.Total of 741 participants were analyzed but 740 participants are presented in this Outcome Measure & 1 participant is presented separately in next Outcome Measure.Only those participants with data available at specified data points were analyzed(n=X in category titles)

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	DTG+3TC FDC	TAF-based regimen
Number of subjects analysed	369 ^[80]	371 ^[81]
Units: Micrograms per liter
arithmetic mean (standard error)
Bone-ALP, Week 24, n=350, 354	-0.77 ( 0.112 )	-1.05 ( 0.089 )
Bone-ALP, Week 48, n=343, 342	-0.03 ( 0.145 )	-0.34 ( 0.117 )
Osteocalcin, Week 24, n=350 ,353	-1.08 ( 0.248 )	0.26 ( 0.229 )
Osteocalcin, Week 48, n=343, 342	-1.15 ( 0.260 )	0.69 ( 0.279 )
P1NP, Week24, n=349 ,356	7.0 ( 0.87 )	5.0 ( 0.72 )
P1NP, Week48, n=342, 343	9.3 ( 1.06 )	6.4 ( 1.00 )
CTX-1, Week 24,n=350,356	0.0350 ( 0.01057 )	-0.0031 ( 0.00833 )
CTX-1, Week 48, n=343, 343	0.0602 ( 0.01024 )	0.0310 ( 0.00889 )

Notes
[80] - Safety Population.
[81] - Safety Population.

Statistical Analysis 1

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for Bone-ALP at Week 24 has been presented

Comparison groups

DTG+3TC FDC v TAF-based regimen

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.047

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

0.29

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.57

Statistical Analysis 2

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for Bone-ALP at Week 48 has been presented

Comparison groups

DTG+3TC FDC v TAF-based regimen

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.094

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

0.31

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

0.68

Statistical Analysis 3

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for Osteocalcin at Week 24 has been presented

Comparison groups

DTG+3TC FDC v TAF-based regimen

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-1.34

Confidence interval

level

95%

sides

2-sided

lower limit

-2.01

upper limit

-0.68

Statistical Analysis 8

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for CTX-1 at Week 48 has been presented

Comparison groups

DTG+3TC FDC v TAF-based regimen

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.032

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

0.0292

Confidence interval

level

95%

sides

2-sided

lower limit

0.0025

upper limit

0.0559

Statistical Analysis 5

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for P1NP at Week 24 has been presented

Comparison groups

DTG+3TC FDC v TAF-based regimen

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.066

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

4.3

Statistical Analysis 6

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for P1NP at Week 48 has been presented.

Comparison groups

DTG+3TC FDC v TAF-based regimen

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.046

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

5.8

Statistical Analysis 7

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for CTX-1 at Week 24 has been presented.

Comparison groups

DTG+3TC FDC v TAF-based regimen

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.005

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

0.0381

Confidence interval

level

95%

sides

2-sided

lower limit

0.0117

upper limit

0.0646

Statistical Analysis 4

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for Osteocalcin at Week 48 has been presented

Comparison groups

DTG+3TC FDC v TAF-based regimen

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-1.84

Confidence interval

level

95%

sides

2-sided

lower limit

-2.59

upper limit

-1.09

Secondary: Change from Baseline in bone biomarkers-serum bone-specific ALP (Bone-ALP), osteocalcin, serum P1NP and serum CTX-1 in participants randomized to TBR arm receiving TDF-based regimen at Weeks 24 and 48

Top of page

End point title

Change from Baseline in bone biomarkers-serum bone-specific ALP (Bone-ALP), osteocalcin, serum P1NP and serum CTX-1 in participants randomized to TBR arm receiving TDF-based regimen at Weeks 24 and 48

End point description

Serum samples were collected for analysis of bone biomarkers. Baseline was latest pre-dose assessment with a non-missing value (Day 1) . Change from Baseline is post-dose visit value minus Baseline value. Change from Baseline in bone biomarkers-serum bone-specific ALP (Bone-ALP), osteocalcin, serum P1NP and serum CTX-1 in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). 99999 indicates data is not available. Data not collected post week 48 as the participant withdrew from the study.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[82]
Units: Micrograms per liter
number (not applicable)
Bone-ALP, Week 24, n=1	0.3
Bone-ALP, Week 48, n=0	99999
Osteocalcin, Week 24, n=1	13.4
Osteocalcin, Week 48, n=0	99999
P1NP, Week24, n=1	11
P1NP, Week48, n=0	99999
CTX-1, Week 24,n=1	0.045
CTX-1, Week 48, n=0	99999

Notes
[82] - Safety Population.

No statistical analyses for this end point

Secondary: Change from Baseline in bone biomarkers-serum Bone-ALP, osteocalcin, serum P1NP and serum type 1 CTX-1 at Weeks 96 and 144

Top of page

End point title

Change from Baseline in bone biomarkers-serum Bone-ALP, osteocalcin, serum P1NP and serum type 1 CTX-1 at Weeks 96 and 144

End point description

Serum samples were collected for analysis of bone biomarkers. Baseline is latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is post-dose visit value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen"). Total of 741 participants were analyzed but 740 participants are presented in this Outcome Measure and 1 participant is presented separately in next Outcome Measure. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[83]	371 ^[84]
Units: Micrograms per liter
arithmetic mean (standard error)
Bone-ALP, Week 96, n=316, 289	-0.62 ( 0.145 )	-0.79 ( 0.137 )
Bone-ALP, Week 144, n=314, 301	-0.27 ( 0.163 )	-0.40 ( 0.177 )
Osteocalcin, Week 96, n=315 , 288	-1.97 ( 0.288 )	-0.10 ( 0.306 )
Osteocalcin, Week 144, n=315, 301	-0.74 ( 0.266 )	1.21 ( 0.320 )
P1NP, Week 96, n=316 ,290	6.7 ( 0.87 )	4.7 ( 0.80 )
P1NP, Week 144, n=315, 302	3.9 ( 0.94 )	3.5 ( 1.04 )
CTX-1, Week 96 ,n=315, 289	0.0201 ( 0.01123 )	0.0050 ( 0.00929 )
CTX-1, Week 48, n=315, 300	0.0022 ( 0.00947 )	-0.0104 ( 0.00907 )

Notes
[83] - Safety Population.
[84] - Safety Population.

Statistical Analysis 2

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for Bone-ALP at Week 144 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.573

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.61

Statistical Analysis 1

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for Bone-ALP at Week 96 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.386

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

0.57

Statistical Analysis 3

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for Osteocalcin at Week 96 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-1.87

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

-1.04

Statistical Analysis 8

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for CTX-1 at Week 144 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.34

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

0.0126

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0133

upper limit

0.0384

Statistical Analysis 6

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for P1NP at Week 144 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.765

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

3.2

Statistical Analysis 5

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for P1NP at Week 96 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.082

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

4.4

Statistical Analysis 4

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for Osteocalcin at Week 144 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-1.95

Confidence interval

level

95%

sides

2-sided

lower limit

-2.77

upper limit

-1.14

Statistical Analysis 7

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for CTX-1 at Week 96 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.301

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

0.0151

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0136

upper limit

0.0438

Secondary: Change from Baseline in bone biomarker: serum 25-hydroxyvitamin D at Weeks 24 and 48

Top of page

End point title

Change from Baseline in bone biomarker: serum 25-hydroxyvitamin D at Weeks 24 and 48

End point description

Serum samples were collected to assess renal biomarker. Baseline was latest pre-dose assessment value with non-missing value (Day 1). Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and its corresponding standard error has been presented. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for following:treatment, visit, Baseline third agent class, CD4+ cell count(continuous), age(continuous), sex, race, BMI(continuous), presence of diabetes mellitus, presence of hypertension, Baseline biomarker(continuous), treatment by visit interaction, & Baseline value by visit interaction, with visit as repeated factor. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen"

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[85]	371 ^[86]
Units: Nanomoles per liter
arithmetic mean (standard error)
Week 24, n=351, 355	0.0 ( 1.10 )	2.1 ( 1.15 )
Week 48, n=344, 343	-5.8 ( 1.21 )	-3.5 ( 1.13 )

Notes
[85] - Safety Population.
[86] - Safety Population.

Statistical Analysis 2

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum 25 hydroxyvitamin D at Week 48 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.168

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.5

upper limit

Statistical Analysis 1

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum 25 hydroxyvitamin D at Week 24 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.173

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-2.2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.3

upper limit

Secondary: Change from Baseline in bone biomarker: serum 25-hydroxyvitamin D at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

Top of page

End point title

Change from Baseline in bone biomarker: serum 25-hydroxyvitamin D at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

End point description

Serum samples were collected for the analysis of 25-hydroxyvitamin D. Baseline value was the value from latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline values for serum 25-hydroxyvitamin D in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen." 99999 indicates data is not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data not collected post week 48 as the participant withdrew from the study.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[87]
Units: Nanomoles per liter
Week 24, n=1	2
Week 48, n=0	99999

Notes
[87] - Safety Population.

No statistical analyses for this end point

Secondary: Change from Baseline in bone biomarker: serum 25-hydroxyvitamin D at Weeks 96 and 144

Top of page

End point title

Change from Baseline in bone biomarker: serum 25-hydroxyvitamin D at Weeks 96 and 144

End point description

Baseline value was (Day 1).Change from Baseline is post-dose visit value minus Baseline value.Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from repeated measures model adjusting for treatment, visit, Baseline third agent class,CD4+ cell count(continuous),age(continuous),sex, race, BMI(continuous),smoking status, vitaminD use,Baseline biomarker(continuous),treatment by visit interaction,& Baseline value by visit interaction, with visit as repeated factor.1 participant randomized to TBR but received TDF & because safety profiles of TDF & TAF differ, participant was removed from overall safety population & is presented in separate arm "Randomized to TBR but received TDF-based regimen.Total of 741 participants were analyzed but 740 participants presented in this Outcome Measure & 1 participant is presented separately in next Outcome Measure. Only those participants with data available at specified data points analyzed(n=X in category titles)

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[88]	371 ^[89]
Units: Nanomoles per liter
arithmetic mean (standard error)
Week 96, n=315, 291	-11.5 ( 1.17 )	-2.2 ( 2.06 )
Week 144, n=315, 303	-7.5 ( 1.28 )	-1.9 ( 1.50 )

Notes
[88] - Safety Population.
[89] - Safety Population.

Statistical Analysis 2

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum 25 hydroxyvitamin D at Week 144 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.005

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-5.6

Confidence interval

level

95%

sides

2-sided

lower limit

-9.4

upper limit

-1.7

Statistical Analysis 1

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum 25 hydroxyvitamin D at Week 96 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-9.4

Confidence interval

level

95%

sides

2-sided

lower limit

-14

upper limit

-4.7

Secondary: Change from Baseline in renal biomarker- serum cystatin C at Weeks 24 and 48

Top of page

End point title

Change from Baseline in renal biomarker- serum cystatin C at Weeks 24 and 48

End point description

Serum samples were collected to assess renal biomarker.Baseline was latest pre-dose assessment value with non-missing value (Day 1).Change from Baseline is post-dose visit value minus Baseline value. Adjusted mean and its corresponding standard error has been presented. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for following:treatment, visit, Baseline third agent class, CD4+ cell count(continuous), age(continuous), sex, race, BMI(continuous), presence of diabetes mellitus, presence of hypertension, Baseline biomarker(continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen"

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[90]	371 ^[91]
Units: Milligrams per liter
arithmetic mean (standard error)
Week 24, n=351, 357	-0.03 ( 0.005 )	-0.02 ( 0.004 )
Week 48, n=344, 343	0.00 ( 0.006 )	0.01 ( 0.005 )

Notes
[90] - Safety Population.
[91] - Safety Population.

Statistical Analysis 2

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum cystatin C at Week 48 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

= 0.061

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

Statistical Analysis 1

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum cystatin C at Week 24 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

= 0.027

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

Secondary: Change from Baseline in renal biomarker- serum cystatin C at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

Top of page

End point title

Change from Baseline in renal biomarker- serum cystatin C at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

End point description

Serum samples were collected at Baseline, Week 24 and Week 48 to assess renal inflammation biomarker - cystatin C. Baseline was defined as the latest pre-dose assessment value with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline values for serum cystatin -C biomarker in TDF based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen."99999 indicates data is not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data not collected post week 48 as the participant withdrew from the study.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[92]
Units: Milligrams per liter
Week 24, n=1	0
Week 48, n=0	99999

Notes
[92] - Safety Population.

No statistical analyses for this end point

Secondary: Change from Baseline in renal biomarker- serum cystatin C at Weeks 96 and 144

Top of page

End point title

Change from Baseline in renal biomarker- serum cystatin C at Weeks 96 and 144

End point description

Change from Baseline is post-dose visit value - Baseline value.Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from repeated measures model adjusting for following:treatment, visit, Baseline third agent class,CD4+ cell count(continuous), age(continuous),sex,race,BMI(continuous),presence of diabetes mellitus, hypertension,Baseline biomarker(continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit repeated factor.1 participant randomized to TBR but received TDF and because safety profiles of TDF and TAF differ, participant was removed from overall safety population and presented in separate arm "Randomized to TBR but received TDF-based regimen." Total of 741 participants were analyzed but 740 participants are presented in this Outcome Measure and 1 participant is presented separately in next Outcome Measure. Participants with data available at specified data points were analyzed(n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[93]	371 ^[94]
Units: Milligrams per liter
arithmetic mean (standard error)
Week 96, n=316, 290	0.07 ( 0.008 )	0.10 ( 0.009 )
Week 144, n=315, 302	0.13 ( 0.006 )	0.14 ( 0.006 )

Notes
[93] - Safety Population.
[94] - Safety Population.

Statistical Analysis 2

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum cystatin C at Week 144 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.094

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

Statistical Analysis 1

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum cystatin C at Week 96 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.004

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.06

upper limit

-0.01

Secondary: Change from Baseline in renal biomarker- serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI at Weeks 24 and 48

Top of page

End point title

Change from Baseline in renal biomarker- serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI at Weeks 24 and 48

End point description

Change from Baseline is post-dose visit value - Baseline value. Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from repeated measures model adjusting for treatment, visit,Baseline third agent class,CD4+ cell count(continuous), age(continuous), sex, race,BMI(continuous), presence of diabetes mellitus, hypertension, Baseline biomarker(continuous), treatment by visit interaction, and Baseline value by visit interaction, with visit as repeated factor. 1 participant randomized to TBR but received TDF and because safety profiles of TDF and TAF differ, participant was removed from overall safety population and presented in separate arm "Randomized to TBR but received TDF-based regimen.” Total of 741 participants were analyzed but 740 participants are presented in this Outcome Measure and 1 participant is presented separately in next Outcome Measure.Participants with data available at specified data points were analyzed (n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[95]	371 ^[96]
Units: Milliliters/minute/1.73*meter square
arithmetic mean (standard error)
GFR from cystatin C CKD-EPI, Week 24, n=351, 357	3.2 ( 0.52 )	1.5 ( 0.46 )
GFR from cystatin C CKD-EPI, Week 48, n=344, 343	0.1 ( 0.61 )	-1.6 ( 0.59 )
GFR from creatinine CKD-EPI, Week 24, n=351, 359	-8.8 ( 0.48 )	-3.8 ( 0.47 )
GFR from creatinine CKD-EPI, Week 48, n=344, 345	-7.7 ( 0.48 )	-2.9 ( 0.48 )

Notes
[95] - Safety Population.
[96] - Safety Population.

Statistical Analysis 1

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum GFR from cystatin C adjusted using CKD-EPI at Week 24 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.012

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

3.1

Statistical Analysis 4

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum GFR from creatinine adjusted using CKD-EPI at Week 48 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-4.8

Confidence interval

level

95%

sides

2-sided

lower limit

-6.1

upper limit

-3.4

Statistical Analysis 3

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum GFR from creatinine adjusted using CKD-EPI at Week 24 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-5

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

-3.7

Statistical Analysis 2

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum GFR from cystatin C adjusted using CKD-EPI at Week 48 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.059

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

3.3

Secondary: Change from Baseline in renal biomarker- serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

Top of page

End point title

Change from Baseline in renal biomarker- serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

End point description

Serum samples were collected to assess renal inflammation biomarkers - serum GFR from cystatin C adjusted using CKD-EPI & serum GFR from creatinine adjusted using CKD-EPI. Baseline was defined as the latest pre-dose assessment value with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline in serum GFR from cystatin C adjusted using CKD-EPI & serum GFR from creatinine adjusted using CKD-EPI in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen & because the safety profiles of TDF & TAF differ, this participant was removed from the overall safety population & is presented in separate arm "Randomized to TBR but received TDF-based regimen.” Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data not collected post week 48 as the participant withdrew from the study.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[97]
Units: Milliliters/minute/1.73*meter square
GFR from cystatin C CKD-EPI, Week 24, n=1	0
GFR from cystatin C CKD-EPI, Week 48, n=0	99999
GFR from creatinine CKD-EPI, Week 24, n=1	4
GFR from creatinine CKD-EPI, Week 48, n=0	99999

Notes
[97] - Safety Population.

No statistical analyses for this end point

Secondary: Change from Baseline in renal biomarker- serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI at Weeks 96 and 144

Top of page

End point title

Change from Baseline in renal biomarker- serum GFR from cystatin C adjusted using CKD-EPI and serum GFR from creatinine adjusted using CKD-EPI at Weeks 96 and 144

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[98]	371 ^[99]
Units: Milliliters/minute/1.73*meter square
arithmetic mean (standard error)
Cystatin C CKD-EPI,Week 96,n=316, 290	-7.6 ( 0.89 )	-11.7 ( 0.99 )
Cystatin C CKD-EPI,Week 144,n=315, 302	-13.9 ( 0.71 )	-15.8 ( 0.70 )
Creatinine adjusted for BSA,Week 96,n=315, 294	-7.2 ( 0.55 )	-1.9 ( 0.52 )
Creatinine adjusted for BSA,Week 144,n=311, 300	-11.5 ( 0.62 )	-7.0 ( 0.60 )

Notes
[98] - Safety Population.
[99] - Safety Population.

Statistical Analysis 1

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum GFR from cystatin C adjusted using CKD-EPI at Week 96 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.002

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

4.1

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

6.7

Statistical Analysis 2

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum GFR from cystatin C adjusted using CKD-EPI at Week 148 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.064

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

3.8

Statistical Analysis 3

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum GFR from creatinine adjusted using CKD-EPI at Week 96 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-5.2

Confidence interval

level

95%

sides

2-sided

lower limit

-6.7

upper limit

-3.8

Statistical Analysis 4

Statistical analysis description

Mean difference (DTG+3TC - TAF based regimen) and its 95% CI for serum GFR from creatinine adjusted using CKD-EPI at Week 144 has been presented

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-4.5

Confidence interval

level

95%

sides

2-sided

lower limit

-6.2

upper limit

-2.8

Secondary: Change from Baseline in renal biomarker- serum creatinine at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

Top of page

End point title

Change from Baseline in renal biomarker- serum creatinine at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

End point description

Serum samples were collected at Baseline, Week 24 and Week 48 to assess renal inflammation biomarker - serum creatinine. Baseline was defined as the latest pre-dose assessment value with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Change from Baseline in serum creatinine in TDF-based regimen participants has been presented. One participant randomized to TBR but received TDF-based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the overall safety population and is presented in separate arm "Randomized to TBR but received TDF-based regimen.”99999 indicates data is not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Data not collected post week 48 as the participant withdrew from the study.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	Randomized to TBR But Received TDF-based Regimen(Early switch)
Number of subjects analysed	1 ^[100]
Units: Micromoles per liter
number (not applicable)
Week 24, n=1	-8
Week 48, n=0	99999

Notes
[100] - Safety Population.

No statistical analyses for this end point

Secondary: Change from Baseline in renal biomarker- serum creatinine at Weeks 24 and 48

Top of page

End point title

Change from Baseline in renal biomarker- serum creatinine at Weeks 24 and 48

End point description

Baseline(Day 1)was value from latest pre-dose assessment with non-missing value.Change from Baseline is post-dose visit value - Baselinevalue.Adjusted mean was estimated mean change from Baseline at each visit in each arm calculated from repeated measures model adjusting for treatment, visit,Baseline third agent class,CD4+ cell count(continuous),age(continuous),sex,race, BMI(continuous),diabetes mellitus,hypertension,Baseline biomarker(continuous),treatment by visit interaction,&Baseline value by visit interaction, with visit as repeated factor. 1participant randomized toTBR butreceived TDF as safety profiles ofTDF & TAFdiffer,participant was removed from safety population & presented in separate arm Randomized to TBR but received TDF-based regimen.Only those participants with data available at specified data points were analyzed(n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[101]	371 ^[102]
Units: Micromoles per liter
arithmetic mean (standard error)
Week 24, n=351, 359	7.47 ( 0.466 )	3.11 ( 0.495 )
Week 48, n=344, 345	6.67 ( 0.493 )	2.18 ( 0.450 )

Notes
[101] - Safety Population.
[102] - Safety Population.

Statistical Analysis 2

Statistical analysis description

Mean difference (DTG+3TC - TBR) and its 95% CI for serum creatinine at Week 48 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

4.49

Confidence interval

level

95%

sides

2-sided

lower limit

3.18

upper limit

5.81

Statistical Analysis 1

Statistical analysis description

Mean difference (DTG+3TC - TBR) and its 95% CI for serum creatinine at Week 24 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

4.37

Confidence interval

level

95%

sides

2-sided

lower limit

3.03

upper limit

5.7

Secondary: Change from Baseline in renal biomarker- serum creatinine at Weeks 96 and 144

Top of page

End point title

Change from Baseline in renal biomarker- serum creatinine at Weeks 96 and 144

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[103]	371 ^[104]
Units: Micromoles per liter
arithmetic mean (standard error)
Week 96, n=316, 294	5.53 ( 0.553 )	0.58 ( 0.515 )
Week 144, n=311, 302	9.25 ( 0.637 )	5.17 ( 0.633 )

Notes
[103] - Safety Population.
[104] - Safety Population.

Statistical Analysis 2

Statistical analysis description

Mean difference (DTG+3TC - TBR) and its 95% CI for serum creatinine at Week 144 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

4.08

Confidence interval

level

95%

sides

2-sided

lower limit

2.32

upper limit

5.85

Statistical Analysis 1

Statistical analysis description

Mean difference (DTG+3TC - TBR) and its 95% CI for serum creatinine at Week 96 has been presented.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

740

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

4.95

Confidence interval

level

95%

sides

2-sided

lower limit

3.47

upper limit

6.43

Secondary: Change from Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) utility score at Week 24 and 48

Top of page

End point title

Change from Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) utility score at Week 24 and 48

End point description

EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. Fiveitem measure has 1 question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. Health state is defined by combining levels of answers from each of 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health. One participant randomized to TBR but received TDF and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable. Only those participants with data available at specified time points has been analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	364 ^[105]	370 ^[106]
Units: Scores on a scale
arithmetic mean (standard error)
Week 24	0.0029 ( 0.00383 )	0.0046 ( 0.00352 )
Week 48	0.0037 ( 0.00407 )	0.0023 ( 0.00373 )

Notes
[105] - ITT-E Population.
[106] - ITT-E Population.

Statistical Analysis 2

Statistical analysis description

Week 48. MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Baseline EQ-5D Utility (continuous), Treatment by Visit interaction, and Baseline EQ-5D Utility by Visit interaction, with Visit as the repeated factor.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

734

Analysis specification

Pre-specified

Analysis type

P-value

= 0.792

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

0.0015

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0094

upper limit

0.0123

Statistical Analysis 1

Statistical analysis description

Week 24. MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Baseline EQ-5D Utility (continuous), Treatment by Visit interaction, and Baseline EQ-5D Utility by Visit interaction, with Visit as the repeated factor.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

734

Analysis specification

Pre-specified

Analysis type

P-value

= 0.741

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.0017

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0119

upper limit

0.0085

Secondary: Change from Baseline in EQ-5D-5L Thermometer scores at Week 24 and 48

Top of page

End point title

Change from Baseline in EQ-5D-5L Thermometer scores at Week 24 and 48

End point description

EEQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). MMRM was run on the LOCF dataset. Baseline was the latest pre-dose assessment value (Day 1) and change from Baseline=post-dose value minus Baseline value. One participant randomized to TBR but received TDF-based regimen and was presented within the “TBR (TAF-based regimen) arm” as efficacy of TAF and TDF are comparable. Participants with data available at specified time points has been analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24 and 48

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	364 ^[107]	369 ^[108]
Units: Scores on a scale
arithmetic mean (standard error)
Week 24	1.2 ( 0.49 )	1.3 ( 0.44 )
Week 48	1.1 ( 0.52 )	1.7 ( 0.43 )

Notes
[107] - ITT-E Population.
[108] - ITT-E Population.

Statistical Analysis 2

Statistical analysis description

Week 48. MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Baseline EQ-5D Thermometer (continuous), Treatment by Visit interaction, and Baseline EQ-5D Thermometer by Visit interaction, with Visit as the repeated factor.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

733

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.414

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.8

Statistical Analysis 1

Statistical analysis description

Week 24. MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Baseline EQ-5D Thermometer (continuous), Treatment by Visit interaction, and Baseline EQ-5D Thermometer by Visit interaction, with Visit as the repeated factor.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

733

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.879

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

1.2

Secondary: Change from Baseline in EQ-5D-5L utility score at Weeks 96 and 144

Top of page

End point title

Change from Baseline in EQ-5D-5L utility score at Weeks 96 and 144

End point description

EQ-5D-5L questionnaire provides profile of participant function and global health state rating. Five-item measure has 1question assessing each of 5dimensions:mobility,self-care,usual activities,pain/discomfort,anxiety/depression and 5 levels for each dimension including 1=no problems,2=slight problems,3=moderate problems,4=severe problems,5=extreme problems. Health state is defined by combining levels of answers from each of 5 questions. Each health state is referred to in terms of a 5 digit code.Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state.EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health.Baseline is latest pre-dose assessment value with a non-missing value (Day 1).Change from Baseline is post-dose visit value minus Baseline value.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[109]	372 ^[110]
Units: Scores on a scale
arithmetic mean (standard error)
Week 96, n=364, 370	-0.0036 ( 0.00442 )	-0.0038 ( 0.00446 )
Week 144, n=364, 369	-0.0151 ( 0.00502 )	-0.0042 ( 0.00492 )

Notes
[109] - ITT-E Population.
[110] - ITT-E Population.

Statistical Analysis 2

Statistical analysis description

Week 144. MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Baseline EQ-5D Utility (continuous), Treatment by Visit interaction, and Baseline EQ-5D Utility by Visit interaction, with Visit as the repeated factor.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

741

Analysis specification

Pre-specified

Analysis type

P-value

= 0.12

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.0109

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0247

upper limit

0.0029

Statistical Analysis 1

Statistical analysis description

Week 96. MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Baseline EQ-5D Utility (continuous), Treatment by Visit interaction, and Baseline EQ-5D Utility by Visit interaction, with Visit as the repeated factor.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

741

Analysis specification

Pre-specified

Analysis type

P-value

= 0.965

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

0.0003

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0121

upper limit

0.0126

Secondary: Change from Baseline in EQ-5D-5L Thermometer scores at Weeks 96 and 144

Top of page

End point title

Change from Baseline in EQ-5D-5L Thermometer scores at Weeks 96 and 144

End point description

EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Baseline is defined as the latest pre-dose assessment value with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. ITT-E Population.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 96 and 144

End point values	DTG+3TC FDC (Early switch)	TAF Based Regimen (Early switch)
Number of subjects analysed	369 ^[111]	372 ^[112]
Units: Scores on a scale
arithmetic mean (standard error)
Week 96, n=364, 369	0.7 ( 0.52 )	1.9 ( 0.48 )
Week 144, n=364, 368	0.2 ( 0.58 )	1.4 ( 0.50 )

Notes
[111] - ITT-E Population.
[112] - ITT-E Population.

Statistical Analysis 2

Statistical analysis description

Week 144. MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Baseline EQ-5D Thermometer (continuous), Treatment by Visit interaction, and Baseline EQ-5D Thermometer by Visit interaction, with Visit as the repeated factor.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

741

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.093

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

0.2

Statistical Analysis 1

Statistical analysis description

Week 96. MMRM adjusted for following: Treatment, Visit, Baseline Third Agent Class, Baseline EQ-5D Thermometer (continuous), Treatment by Visit interaction, and Baseline EQ-5D Thermometer by Visit interaction, with Visit as the repeated factor.

Comparison groups

DTG+3TC FDC (Early switch) v TAF Based Regimen (Early switch)

Number of subjects included in analysis

741

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.102

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

0.2

Adverse events

Top of page

Timeframe for reporting adverse events

TAF Based Regimen EarlySwitch uptoWeek 148; Randomized to TBR but received TDFbased regimen uptoweek 48;DTG+3TC FDC Early+Late Switch-Overall uptoWeek 196, TAF Based Regimen(Early Switch) then DTG+3TC FDC(Late Switch) from Week 148 to Week 196

Adverse event reporting additional description

Safety Population. 1 participant randomized to TBR received TDF based regimen and because the safety profiles of TDF and TAF differ, this participant was removed from the safety population & is presented in separate arm "Randomized to TBR but received TDF-based regimen (Early switch)”

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.0

Reporting group title

TAF Based Regimen (Early Switch)

Reporting group description

Participants who were on a stable TBR and who had an HIV-1 RNA<50 c/mL at the time of screening, were continued to receive TBR up to 148 weeks during early switch phase.

Reporting group title

DTG + 3TC FDC (Early Switch + Late Switch)-Overall

Reporting group description

Participants who were on a stable TBR and who had an HIV-1 ribonucleic acid (RNA) <50 copies per millilter (c/mL) at the time of screening, received fixed dose combination of DTG 50 mg + 3TC 300 mg once daily up to 196 weeks during early and late switch phase.

Reporting group title

TAF Based Regimen(Early Switch) then DTG+3TC FDC(Late Switch)

Reporting group description

Participants who were on a stable TBR and who had an HIV-1 RNA<50 c/mL at the time of screening, were continued to receive TBR up to 148 weeks during early switch phase. At Week 148 (or upon retest) were switched to DTG/3TC FDC once daily up to Week 196 during late switch phase.

Reporting group title

Randomized to TBR but received TDF-based regimen(Early Switch)

Reporting group description

Serious adverse events	TAF Based Regimen (Early Switch)	DTG + 3TC FDC (Early Switch + Late Switch)-Overall	TAF Based Regimen(Early Switch) then DTG+3TC FDC(Late Switch)	Randomized to TBR but received TDF-based regimen(Early Switch)
Total subjects affected by serious adverse events
subjects affected / exposed	44 / 371 (11.86%)	65 / 369 (17.62%)	15 / 298 (5.03%)	0 / 1 (0.00%)
number of deaths (all causes)	0	4	0	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lung adenocarcinoma
subjects affected / exposed	0 / 371 (0.00%)	2 / 369 (0.54%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diffuse large B-cell lymphoma
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to liver
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Penile squamous cell carcinoma
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hodgkin's disease
subjects affected / exposed	0 / 371 (0.00%)	3 / 369 (0.81%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Burkitt's lymphoma stage I
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal tract adenoma
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of lung
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Small intestine adenocarcinoma
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Adenocarcinoma of colon
subjects affected / exposed	0 / 371 (0.00%)	0 / 369 (0.00%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Transitional cell carcinoma
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Salivary gland neoplasm
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal cell carcinoma
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	1 / 371 (0.27%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatic carcinoma
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	1 / 371 (0.27%)	1 / 369 (0.27%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypovolaemic shock
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive crisis
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Premature labour
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Type I hypersensitivity
subjects affected / exposed	0 / 371 (0.00%)	0 / 369 (0.00%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian haematoma
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian cyst
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostatitis
subjects affected / exposed	2 / 371 (0.54%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Priapism
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	3 / 371 (0.81%)	2 / 369 (0.54%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vocal cord cyst
subjects affected / exposed	0 / 371 (0.00%)	0 / 369 (0.00%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary hypertension
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atelectasis
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	2 / 371 (0.54%)	2 / 369 (0.54%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anxiety
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	2 / 371 (0.54%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	1 / 371 (0.27%)	2 / 369 (0.54%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bipolar disorder
subjects affected / exposed	3 / 371 (0.81%)	0 / 369 (0.00%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bipolar II disorder
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Major depression
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Substance abuse
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Injury, poisoning and procedural complications
Gun shot wound
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Overdose
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Craniocerebral injury
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wrist fracture
subjects affected / exposed	0 / 371 (0.00%)	0 / 369 (0.00%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wound evisceration
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	1 / 371 (0.27%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural haematoma
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Hydrocele
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	1 / 371 (0.27%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ventricular tachycardia
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebral haematoma
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 371 (0.00%)	4 / 369 (1.08%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sciatica
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Leukoencephalopathy
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hemiplegic migraine
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bell's palsy
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Loss of consciousness
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Inguinal hernia
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	2 / 371 (0.54%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal hernia
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	1 / 371 (0.27%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	2 / 371 (0.54%)	2 / 369 (0.54%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	2 / 371 (0.54%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Biliary dyskinesia
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	1 / 371 (0.27%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertransaminasaemia
subjects affected / exposed	0 / 371 (0.00%)	2 / 369 (0.54%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic hepatitis
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Angioedema
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Calculus urinary
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute kidney injury
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Osteitis
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 371 (0.00%)	2 / 369 (0.54%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nose deformity
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sacroiliac joint dysfunction
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cervical spinal stenosis
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	1 / 371 (0.27%)	3 / 369 (0.81%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	1 / 371 (0.27%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Amniotic cavity infection
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Labyrinthitis
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis pneumococcal
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Shigella infection
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pertussis
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis intestinal perforated
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis gonococcal
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	2 / 371 (0.54%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 371 (0.00%)	2 / 369 (0.54%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	2 / 371 (0.54%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	2 / 371 (0.54%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Scrotal abscess
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal infection
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal abscess
subjects affected / exposed	0 / 371 (0.00%)	0 / 369 (0.00%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute hepatitis C
subjects affected / exposed	0 / 371 (0.00%)	0 / 369 (0.00%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis
subjects affected / exposed	0 / 371 (0.00%)	0 / 369 (0.00%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Groin abscess
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal abscess
subjects affected / exposed	0 / 371 (0.00%)	0 / 369 (0.00%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Perirectal abscess
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Perineal abscess
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	1 / 371 (0.27%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 371 (0.00%)	0 / 369 (0.00%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syphilis
subjects affected / exposed	0 / 371 (0.00%)	0 / 369 (0.00%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypokalaemia
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertriglyceridaemia
subjects affected / exposed	0 / 371 (0.00%)	1 / 369 (0.27%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	TAF Based Regimen (Early Switch)	DTG + 3TC FDC (Early Switch + Late Switch)-Overall	TAF Based Regimen(Early Switch) then DTG+3TC FDC(Late Switch)	Randomized to TBR but received TDF-based regimen(Early Switch)
Total subjects affected by non serious adverse events
subjects affected / exposed	304 / 371 (81.94%)	327 / 369 (88.62%)	187 / 298 (62.75%)	1 / 1 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts
subjects affected / exposed	10 / 371 (2.70%)	9 / 369 (2.44%)	3 / 298 (1.01%)	0 / 1 (0.00%)
occurrences all number	11	10	3	0
Vascular disorders
Hypertension
subjects affected / exposed	15 / 371 (4.04%)	26 / 369 (7.05%)	7 / 298 (2.35%)	0 / 1 (0.00%)
occurrences all number	15	28	7	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	11 / 371 (2.96%)	32 / 369 (8.67%)	11 / 298 (3.69%)	0 / 1 (0.00%)
occurrences all number	12	33	11	0
Chest pain
subjects affected / exposed	9 / 371 (2.43%)	9 / 369 (2.44%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences all number	10	10	1	0
Influenza like illness
subjects affected / exposed	13 / 371 (3.50%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	16	0	0	0
Pyrexia
subjects affected / exposed	14 / 371 (3.77%)	19 / 369 (5.15%)	7 / 298 (2.35%)	0 / 1 (0.00%)
occurrences all number	15	20	8	0
Immune system disorders
Seasonal allergy
subjects affected / exposed	4 / 371 (1.08%)	15 / 369 (4.07%)	3 / 298 (1.01%)	0 / 1 (0.00%)
occurrences all number	5	18	3	0
Reproductive system and breast disorders
Erectile dysfunction
subjects affected / exposed	19 / 371 (5.12%)	15 / 369 (4.07%)	3 / 298 (1.01%)	0 / 1 (0.00%)
occurrences all number	20	15	3	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	20 / 371 (5.39%)	27 / 369 (7.32%)	5 / 298 (1.68%)	0 / 1 (0.00%)
occurrences all number	21	30	5	0
Oropharyngeal pain
subjects affected / exposed	17 / 371 (4.58%)	15 / 369 (4.07%)	2 / 298 (0.67%)	0 / 1 (0.00%)
occurrences all number	17	19	2	0
Psychiatric disorders
Anxiety
subjects affected / exposed	29 / 371 (7.82%)	43 / 369 (11.65%)	7 / 298 (2.35%)	0 / 1 (0.00%)
occurrences all number	30	44	8	0
Insomnia
subjects affected / exposed	18 / 371 (4.85%)	29 / 369 (7.86%)	7 / 298 (2.35%)	0 / 1 (0.00%)
occurrences all number	18	34	8	0
Depression
subjects affected / exposed	21 / 371 (5.66%)	31 / 369 (8.40%)	6 / 298 (2.01%)	0 / 1 (0.00%)
occurrences all number	24	32	6	0
Investigations
Weight increased
subjects affected / exposed	19 / 371 (5.12%)	9 / 369 (2.44%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences all number	19	9	1	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	8 / 371 (2.16%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	9	0	0	0
Ligament sprain
subjects affected / exposed	0 / 371 (0.00%)	8 / 369 (2.17%)	5 / 298 (1.68%)	0 / 1 (0.00%)
occurrences all number	0	8	5	0
Arthropod bite
subjects affected / exposed	8 / 371 (2.16%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	9	0	0	0
Muscle strain
subjects affected / exposed	4 / 371 (1.08%)	8 / 369 (2.17%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences all number	4	8	1	0
Limb injury
subjects affected / exposed	8 / 371 (2.16%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	8	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	23 / 371 (6.20%)	41 / 369 (11.11%)	17 / 298 (5.70%)	0 / 1 (0.00%)
occurrences all number	33	54	20	0
Dizziness
subjects affected / exposed	11 / 371 (2.96%)	15 / 369 (4.07%)	5 / 298 (1.68%)	0 / 1 (0.00%)
occurrences all number	11	15	5	0
Migraine
subjects affected / exposed	5 / 371 (1.35%)	9 / 369 (2.44%)	2 / 298 (0.67%)	0 / 1 (0.00%)
occurrences all number	5	10	2	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	8 / 371 (2.16%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	8	0	0	0
Vertigo
subjects affected / exposed	0 / 371 (0.00%)	8 / 369 (2.17%)	3 / 298 (1.01%)	0 / 1 (0.00%)
occurrences all number	0	8	3	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	43 / 371 (11.59%)	54 / 369 (14.63%)	12 / 298 (4.03%)	1 / 1 (100.00%)
occurrences all number	55	70	12	1
Vomiting
subjects affected / exposed	6 / 371 (1.62%)	12 / 369 (3.25%)	2 / 298 (0.67%)	0 / 1 (0.00%)
occurrences all number	6	12	2	0
Constipation
subjects affected / exposed	7 / 371 (1.89%)	15 / 369 (4.07%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences all number	7	19	1	0
Toothache
subjects affected / exposed	16 / 371 (4.31%)	13 / 369 (3.52%)	4 / 298 (1.34%)	0 / 1 (0.00%)
occurrences all number	19	15	5	0
Abdominal pain
subjects affected / exposed	14 / 371 (3.77%)	19 / 369 (5.15%)	2 / 298 (0.67%)	0 / 1 (0.00%)
occurrences all number	15	21	2	0
Nausea
subjects affected / exposed	18 / 371 (4.85%)	23 / 369 (6.23%)	4 / 298 (1.34%)	0 / 1 (0.00%)
occurrences all number	20	25	4	0
Gastrooesophageal reflux disease
subjects affected / exposed	9 / 371 (2.43%)	20 / 369 (5.42%)	6 / 298 (2.01%)	0 / 1 (0.00%)
occurrences all number	12	20	6	0
Haemorrhoids
subjects affected / exposed	12 / 371 (3.23%)	14 / 369 (3.79%)	5 / 298 (1.68%)	0 / 1 (0.00%)
occurrences all number	12	14	5	0
Abdominal pain upper
subjects affected / exposed	9 / 371 (2.43%)	11 / 369 (2.98%)	3 / 298 (1.01%)	0 / 1 (0.00%)
occurrences all number	9	13	3	0
Dyspepsia
subjects affected / exposed	5 / 371 (1.35%)	10 / 369 (2.71%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences all number	5	10	1	0
Abdominal distension
subjects affected / exposed	6 / 371 (1.62%)	10 / 369 (2.71%)	2 / 298 (0.67%)	0 / 1 (0.00%)
occurrences all number	6	11	2	0
Proctalgia
subjects affected / exposed	9 / 371 (2.43%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	9	0	0	0
Dental caries
subjects affected / exposed	8 / 371 (2.16%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	9	0	0	0
Gastritis
subjects affected / exposed	0 / 371 (0.00%)	9 / 369 (2.44%)	3 / 298 (1.01%)	0 / 1 (0.00%)
occurrences all number	0	9	3	0
Skin and subcutaneous tissue disorders
Eczema
subjects affected / exposed	0 / 371 (0.00%)	8 / 369 (2.17%)	2 / 298 (0.67%)	0 / 1 (0.00%)
occurrences all number	0	12	2	0
Dry skin
subjects affected / exposed	8 / 371 (2.16%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	9	0	0	0
Dermatitis
subjects affected / exposed	10 / 371 (2.70%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	10	0	0	0
Rash
subjects affected / exposed	11 / 371 (2.96%)	15 / 369 (4.07%)	3 / 298 (1.01%)	0 / 1 (0.00%)
occurrences all number	11	17	3	0
Pruritus
subjects affected / exposed	12 / 371 (3.23%)	11 / 369 (2.98%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences all number	13	11	1	0
Dermatitis contact
subjects affected / exposed	0 / 371 (0.00%)	8 / 369 (2.17%)	2 / 298 (0.67%)	0 / 1 (0.00%)
occurrences all number	0	8	2	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 371 (0.00%)	9 / 369 (2.44%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences all number	0	9	1	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	49 / 371 (13.21%)	47 / 369 (12.74%)	11 / 298 (3.69%)	0 / 1 (0.00%)
occurrences all number	63	53	12	0
Arthralgia
subjects affected / exposed	39 / 371 (10.51%)	46 / 369 (12.47%)	15 / 298 (5.03%)	0 / 1 (0.00%)
occurrences all number	43	56	17	0
Pain in extremity
subjects affected / exposed	14 / 371 (3.77%)	23 / 369 (6.23%)	6 / 298 (2.01%)	0 / 1 (0.00%)
occurrences all number	17	25	7	0
Myalgia
subjects affected / exposed	0 / 371 (0.00%)	11 / 369 (2.98%)	4 / 298 (1.34%)	0 / 1 (0.00%)
occurrences all number	0	11	4	0
Neck pain
subjects affected / exposed	6 / 371 (1.62%)	9 / 369 (2.44%)	5 / 298 (1.68%)	0 / 1 (0.00%)
occurrences all number	6	11	5	0
Muscle spasms
subjects affected / exposed	9 / 371 (2.43%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	10	0	0	0
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	42 / 371 (11.32%)	52 / 369 (14.09%)	7 / 298 (2.35%)	1 / 1 (100.00%)
occurrences all number	56	72	7	1
Nasopharyngitis
subjects affected / exposed	64 / 371 (17.25%)	71 / 369 (19.24%)	16 / 298 (5.37%)	0 / 1 (0.00%)
occurrences all number	93	109	18	0
Syphilis
subjects affected / exposed	33 / 371 (8.89%)	49 / 369 (13.28%)	13 / 298 (4.36%)	0 / 1 (0.00%)
occurrences all number	43	61	13	0
Pharyngitis
subjects affected / exposed	22 / 371 (5.93%)	21 / 369 (5.69%)	5 / 298 (1.68%)	0 / 1 (0.00%)
occurrences all number	25	22	5	0
Bronchitis
subjects affected / exposed	23 / 371 (6.20%)	17 / 369 (4.61%)	5 / 298 (1.68%)	0 / 1 (0.00%)
occurrences all number	24	19	5	0
Gastroenteritis
subjects affected / exposed	23 / 371 (6.20%)	29 / 369 (7.86%)	5 / 298 (1.68%)	0 / 1 (0.00%)
occurrences all number	26	37	5	0
Oral herpes
subjects affected / exposed	12 / 371 (3.23%)	10 / 369 (2.71%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	12	12	0	0
Proctitis gonococcal
subjects affected / exposed	11 / 371 (2.96%)	15 / 369 (4.07%)	4 / 298 (1.34%)	0 / 1 (0.00%)
occurrences all number	15	20	5	0
Urethritis
subjects affected / exposed	13 / 371 (3.50%)	16 / 369 (4.34%)	5 / 298 (1.68%)	0 / 1 (0.00%)
occurrences all number	14	21	5	0
Urinary tract infection
subjects affected / exposed	12 / 371 (3.23%)	16 / 369 (4.34%)	3 / 298 (1.01%)	0 / 1 (0.00%)
occurrences all number	14	19	4	0
Influenza
subjects affected / exposed	14 / 371 (3.77%)	18 / 369 (4.88%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	14	18	0	0
COVID-19
subjects affected / exposed	25 / 371 (6.74%)	76 / 369 (20.60%)	55 / 298 (18.46%)	0 / 1 (0.00%)
occurrences all number	25	79	57	0
Anal chlamydia infection
subjects affected / exposed	22 / 371 (5.93%)	13 / 369 (3.52%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	31	16	0	0
Chlamydial infection
subjects affected / exposed	12 / 371 (3.23%)	21 / 369 (5.69%)	6 / 298 (2.01%)	0 / 1 (0.00%)
occurrences all number	12	23	6	0
Oropharyngeal gonococcal infection
subjects affected / exposed	15 / 371 (4.04%)	16 / 369 (4.34%)	3 / 298 (1.01%)	0 / 1 (0.00%)
occurrences all number	16	22	3	0
Sinusitis
subjects affected / exposed	15 / 371 (4.04%)	13 / 369 (3.52%)	2 / 298 (0.67%)	0 / 1 (0.00%)
occurrences all number	17	15	2	0
Conjunctivitis
subjects affected / exposed	8 / 371 (2.16%)	16 / 369 (4.34%)	2 / 298 (0.67%)	0 / 1 (0.00%)
occurrences all number	10	19	2	0
Folliculitis
subjects affected / exposed	14 / 371 (3.77%)	0 / 369 (0.00%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	16	0	0	0
Gonorrhoea
subjects affected / exposed	9 / 371 (2.43%)	12 / 369 (3.25%)	5 / 298 (1.68%)	0 / 1 (0.00%)
occurrences all number	10	15	7	0
Tonsillitis
subjects affected / exposed	10 / 371 (2.70%)	8 / 369 (2.17%)	2 / 298 (0.67%)	0 / 1 (0.00%)
occurrences all number	12	13	2	0
Respiratory tract infection
subjects affected / exposed	9 / 371 (2.43%)	9 / 369 (2.44%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences all number	9	11	1	0
Tooth infection
subjects affected / exposed	10 / 371 (2.70%)	10 / 369 (2.71%)	7 / 298 (2.35%)	0 / 1 (0.00%)
occurrences all number	12	13	8	0
Urethritis gonococcal
subjects affected / exposed	4 / 371 (1.08%)	15 / 369 (4.07%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	4	16	0	0
Onychomycosis
subjects affected / exposed	6 / 371 (1.62%)	10 / 369 (2.71%)	2 / 298 (0.67%)	0 / 1 (0.00%)
occurrences all number	7	11	2	0
Rhinitis
subjects affected / exposed	2 / 371 (0.54%)	9 / 369 (2.44%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences all number	2	9	1	0
Fungal skin infection
subjects affected / exposed	11 / 371 (2.96%)	8 / 369 (2.17%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	13	10	0	0
Proctitis chlamydial
subjects affected / exposed	0 / 371 (0.00%)	14 / 369 (3.79%)	2 / 298 (0.67%)	0 / 1 (0.00%)
occurrences all number	0	23	2	0
Suspected COVID-19
subjects affected / exposed	0 / 371 (0.00%)	8 / 369 (2.17%)	2 / 298 (0.67%)	0 / 1 (0.00%)
occurrences all number	0	9	2	0
Tinea versicolour
subjects affected / exposed	0 / 371 (0.00%)	8 / 369 (2.17%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences all number	0	11	1	0
Urethritis chlamydial
subjects affected / exposed	0 / 371 (0.00%)	8 / 369 (2.17%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences all number	0	11	1	0
Herpes zoster
subjects affected / exposed	0 / 371 (0.00%)	8 / 369 (2.17%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	8	0	0
Metabolism and nutrition disorders
Vitamin D deficiency
subjects affected / exposed	12 / 371 (3.23%)	22 / 369 (5.96%)	5 / 298 (1.68%)	0 / 1 (0.00%)
occurrences all number	15	23	5	0
Hypercholesterolaemia
subjects affected / exposed	0 / 371 (0.00%)	9 / 369 (2.44%)	0 / 298 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	9	0	0
Hyperlipidaemia
subjects affected / exposed	0 / 371 (0.00%)	9 / 369 (2.44%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences all number	0	9	1	0
Abnormal loss of weight
subjects affected / exposed	0 / 371 (0.00%)	10 / 369 (2.71%)	1 / 298 (0.34%)	0 / 1 (0.00%)
occurrences all number	0	10	2	0
Abnormal weight gain
subjects affected / exposed	0 / 371 (0.00%)	12 / 369 (3.25%)	4 / 298 (1.34%)	0 / 1 (0.00%)
occurrences all number	0	12	4	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

16 May 2017

Amendment 01: TAF was corrected by removal of the word “fumarate”. Clarification was provided in the overall design to specify that participants randomized to TBR will switch to DTG/3TC FDC at Week 52 if human immunodeficiency virus-1 ribonucleic acid (HIV-1 RNA) <50 copies per milliliter (c/mL) at Week 48 (or upon retest by Week 52). Biomarkers of inflammation and mitochondrial function were removed as exploratory endpoints. A Week 96 endpoint was added to the measurement of biomarkers of telomerase function in a subset of participants. Cardiovascular biomarker measurements were removed as exploratory endpoints. Inclusion Criteria #5 was edited for clarity. Protocol Section 6.2, Protocol Permitted Substitutions, added. The text defining the TBR comparators as investigational medicinal product was removed; TBR comparators are provided in designated, specific countries only, as needed. The Time and Events Table was modified to clarify that whole blood samples could be utilized for virology and for telomere length measurements, and cryopreserved peripheral blood mononuclear cells (PBMCs) could be used to evaluate telomerase activity. Updated version of Division of acquires immunodeficiency syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (version 2.1), March 2017, was provided in Protocol Section 12.9. Changes were made to the protocol text to reflect the addition of Country Specific requirements for Japan.

13 Jun 2017

Amendment 02: The impetus for this protocol amendment was to update Protocol Appendix 5, Protocol Appendix 6 and Protocol Appendix 8 based on the ViiV Healthcare templates for these appendices that were appropriate for the HIV participant population.

24 Aug 2017

Amendment 03: Amended to include: Addition of cluster of differentiation 8 plus (CD8+) lymphocyte assessments, addition of inflammatory biomarkers assessments as new exploratory endpoints, and revision of the sample size based on updated estimates for the primary endpoint for the investigational arm.

07 Dec 2017

Amendment 04: Amended to include pharmacokinetics assessments in the DTG/3TC FDC arm as exploratory endpoints; to update exclusion criterion 18 and remove its corresponding secondary endpoint no longer relevant; and to add glycated hemoglobin (HbA1c) and homeostasis model of assessment-insulin resistance (HOMA-IR) assessments. For clarification purposes, the adverse event (AE) severity grading in Protocol Appendix 8 and Protocol Section 13.8.6 (Evaluating AEs and serious adverse events [SAEs]) were updated to be consistent with Protocol Appendix 9, Protocol Section 13.9 (Division of AIDS table for Grading Severity of Adult and Pediatric Adverse Events). This change has no impact on the investigator’s evaluation of adverse events. Text was edited in Protocol Appendix 10, Protocol Section 13.10.2 to clarify wording for the country specific requirement for Japan.

14 Jun 2018

Amendment 05: Changes were made to the protocol to manage and mitigate risks following identification of a potential safety issue related to neural tube defects in infants born to women with exposure to DTG at the time of conception. Changes were also made to include updated text to address a higher number of participants screened than planned, to update references to the DTG Investigator’s Brochure (IB) to reflect the most current versions and to add clarification and correct minor typos. The Risk Assessment table (Protocol Section 4.6.1) was updated to include language regarding risk and mitigation of neural tube defects. The withdrawal criteria (Protocol Section 5.4) were updated to include a reminder that females of reproductive potential who change their minds and desire to be pregnant, or who state they no longer are willing to comply with the approved pregnancy avoidance methods, would also be withdrawn from the study. The Time and Events table (Protocol Section 7.1) was updated to include a reminder for investigators to check at every visit that females of reproductive potential are avoiding pregnancy. The modified list of highly effective methods for avoiding pregnancy in females of reproductive potential (FRP) (Protocol Section 13.3.1) was updated to exclude the double barrier method of contraception, which does not meet the updated GlaxoSmithKline [GSK]/ViiV criteria for a highly effective method. The Type and Number of participants (Protocol Section 4.3) and Sample Size Assumptions (Protocol Section 9.2.1) were updated to address a higher number of participants screened than planned.

29 Aug 2018

Amendment 06: Changes were made to the protocol to update the study design to extend the Randomized Early Switch Phase through to 148 weeks instead of Week 52, delaying the late switch to Week 148 with long-term follow-up through to completion of the study at Week 200. The rationale for this change was to collect and assess long-term comparative efficacy and safety data for DTG/3TC FDC vs. a TAF-based regimen.

27 Apr 2020

Amendment 07: Changes were made to the protocol to introduce metabolic health exploratory objectives including metabolic syndrome, cardiovascular risk and other anthropomorphic measures to assess type and implication of weight change overtime. Additional on-treatment assessments from Week 144 through Week 196, include resting blood pressure, waist circumference and hip circumference. Changes were also made to include an additional appendix to provide standardized procedural guidance on obtaining the above mentioned measurements. A missing assessment of concomitant medication at Week 148 was also corrected. Results from the Botswana outcome surveillance study were updated for DTG and neural tube defects.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase III, randomized, multicenter, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of switching to dolutegravir plus lamivudine in HIV-1 infected adults who are virologically suppressed

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants with virologic failure endpoint as per Food and Drug Administration (FDA) snapshot category at Week 48

Primary: Percentage of participants with virologic failure endpoint as per Food and Drug Administration (FDA) snapshot category at Week 48

Secondary: Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Week 48

Secondary: Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Week 48

Secondary: Percentage of participants with virologic failure endpoint as per FDA snapshot category at Week 24

Secondary: Percentage of participants with virologic failure endpoint as per FDA snapshot category at Week 24

Secondary: Percentage of participants with virologic failure endpoint as per FDA snapshot category at Weeks 96, 144

Secondary: Percentage of participants with virologic failure endpoint as per FDA snapshot category at Weeks 96, 144

Secondary: Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Week 24

Secondary: Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Week 24

Secondary: Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Weeks 96 and 144

Secondary: Percentage of participants with plasma HIV-1 RNA <50 c/mL as per snapshot algorithm at Weeks 96 and 144

Secondary: Change from Baseline in CD4+ cell count at Weeks 24 and 48

Secondary: Change from Baseline in CD4+ cell count at Weeks 24 and 48

Secondary: Change from Baseline in CD4+/CD8+ cell count ratio at Weeks 24 and 48

Secondary: Change from Baseline in CD4+/CD8+ cell count ratio at Weeks 24 and 48

Secondary: Change from Baseline in CD4+/CD8+ cell count ratio at Weeks 96 and 144

Secondary: Change from Baseline in CD4+/CD8+ cell count ratio at Weeks 96 and 144

Secondary: Change from Baseline in CD4+ cell count at Weeks 96 and 144

Secondary: Change from Baseline in CD4+ cell count at Weeks 96 and 144

Secondary: Number of participants with disease progression at Weeks 24 and 48

Secondary: Number of participants with disease progression at Weeks 24 and 48

Secondary: Number of participants with disease progression at Weeks 96 and 144

Secondary: Number of participants with disease progression at Weeks 96 and 144

Secondary: Number of participants with any serious adverse events (SAEs) and common (>=2%) non-serious adverse events (non-SAEs): Up to Week 48

Secondary: Number of participants with any serious adverse events (SAEs) and common (>=2%) non-serious adverse events (non-SAEs): Up to Week 48

Secondary: Number of Participants with AEs by their severity Grades: Up to Week 48

Secondary: Number of Participants with AEs by their severity Grades: Up to Week 48

Secondary: Number of participants with any SAEs and common (>=2%) non-SAEs: Up to Week 148

Secondary: Number of participants with any SAEs and common (>=2%) non-SAEs: Up to Week 148

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with any SAEs and common (>=2%) non-SAEs: Up to Week 48

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with any SAEs and common (>=2%) non-SAEs: Up to Week 48

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with AEs by their severity Grades: Up to Week 48

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with AEs by their severity Grades: Up to Week 48

Secondary: Number of Participants With AEs by Their Severity Grades: Up to Week 144

Secondary: Number of Participants With AEs by Their Severity Grades: Up to Week 144

Secondary: Number of participants who discontinued the treatment due to AEs: Up to Week 48

Secondary: Number of participants who discontinued the treatment due to AEs: Up to Week 48

Secondary: Number of participants who discontinued the treatment due to AEs: Up to Week 144

Secondary: Number of participants who discontinued the treatment due to AEs: Up to Week 144

Secondary: Number of participants with Maximum Post-Baseline emergent hematology toxicities: Up to Week 48

Secondary: Number of participants with Maximum Post-Baseline emergent hematology toxicities: Up to Week 48

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen who discontinued the treatment due to AEs: Up to Week 48

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen who discontinued the treatment due to AEs: Up to Week 48

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with Maximum Post-Baseline emergent hematology toxicities: Up to Week 36

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with Maximum Post-Baseline emergent hematology toxicities: Up to Week 36

Secondary: Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities: Up to Week 144

Secondary: Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities: Up to Week 144

Secondary: Number of participants with Maximum Post-Baseline emergent clinical chemistry toxicities: Up to Week 48

Secondary: Number of participants with Maximum Post-Baseline emergent clinical chemistry toxicities: Up to Week 48

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with Maximum Post-Baseline emergent clinical chemistry toxicities: Up to Week 36

Secondary: Number of participants randomized to TBR arm receiving TDF-based regimen with Maximum Post-Baseline emergent clinical chemistry toxicities: Up to Week 36

Secondary: Number of participants with Maximum Post-Baseline emergent clinical chemistry toxicities: Up to Week 144

Secondary: Number of participants with Maximum Post-Baseline emergent clinical chemistry toxicities: Up to Week 144

Secondary: Change from Baseline in renal biomarkers- Urine albumin/creatinine (UA/C) ratio and Urine protein/creatinine (UP/C) ratio at Weeks 24 and 48

Secondary: Change from Baseline in renal biomarkers- Urine albumin/creatinine (UA/C) ratio and Urine protein/creatinine (UP/C) ratio at Weeks 24 and 48

Secondary: Change from Baseline in renal biomarkers- UA/C ratio and UP/C ratio at Weeks 24 and 48 in participants randomized to TBR receiving TDF-based regimen

Secondary: Change from Baseline in renal biomarkers- UA/C ratio and UP/C ratio at Weeks 24 and 48 in participants randomized to TBR receiving TDF-based regimen

Secondary: Change from Baseline in renal biomarkers- UA/C ratio and UP/C ratio at Weeks 96 and 144

Secondary: Change from Baseline in renal biomarkers- UA/C ratio and UP/C ratio at Weeks 96 and 144

Secondary: Change from Baseline in renal biomarkers- Urine beta-2 microglobulin/urine creatinine ratio at Weeks 24 and 48

Secondary: Change from Baseline in renal biomarkers- Urine beta-2 microglobulin/urine creatinine ratio at Weeks 24 and 48

Secondary: Change from Baseline in renal biomarkers- Urine phosphate at Weeks 24 and 48

Secondary: Change from Baseline in renal biomarkers- Urine phosphate at Weeks 24 and 48

Secondary: Change from Baseline in renal biomarkers- Urine beta-2 microglobulin/urine creatinine ratio at Weeks 96 and 144

Secondary: Change from Baseline in renal biomarkers- Urine beta-2 microglobulin/urine creatinine ratio at Weeks 96 and 144

Secondary: Change from Baseline in renal biomarkers- Urine phosphate at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

Secondary: Change from Baseline in renal biomarkers- Urine phosphate at Weeks 24 and 48 in participants randomized to TBR arm receiving TDF-based regimen

Secondary: Change from Baseline in renal biomarkers- Urine phosphate at Weeks 96 and 144

Secondary: Change from Baseline in renal biomarkers- Urine phosphate at Weeks 96 and 144

Clinical Trial Results:
A Phase III, randomized, multicenter, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of switching to dolutegravir plus lamivudine in HIV-1 infected adults who are virologically suppressed