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Clinical Trial Results:
A Phase III, randomised, double-blind, multicentre, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of dolutegravir plus lamivudine compared to dolutegravir plus tenofovir/emtricitabine in HIV-1-infected treatment-naïve adults

Summary
EudraCT number	2016-000459-28
Trial protocol	DE BE PT ES FR IT
Global end of trial date	29 Jun 2022

Results information
Results version number	v3(current)
This version publication date	16 Aug 2023
First version publication date	13 Apr 2019
Other versions	v1 , v2
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

205543

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

22 Aug 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

29 Jun 2022

Was the trial ended prematurely?

Main objective of the trial

To demonstrate non-inferior antiviral activity of Dolutegravir (DTG) + Lamivudine (3TC) versus DTG + Tenofovir disoproxil fumarate/ Emtricitabine (TDF/FTC) at 48 weeks in human immunodeficiency virus (HIV)-1-infected, Antiretroviral therapy (ART)-naïve participants

Protection of trial subjects

Not applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

18 Jul 2016

Long term follow-up planned

Yes

Long term follow-up rationale

Ethical reason

Long term follow-up duration

4 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 77

Country: Number of subjects enrolled

Australia: 14

Country: Number of subjects enrolled

Belgium: 8

Country: Number of subjects enrolled

Canada: 13

Country: Number of subjects enrolled

France: 10

Country: Number of subjects enrolled

Germany: 16

Country: Number of subjects enrolled

Italy: 52

Country: Number of subjects enrolled

Mexico: 43

Country: Number of subjects enrolled

Peru: 23

Country: Number of subjects enrolled

Poland: 9

Country: Number of subjects enrolled

Portugal: 20

Country: Number of subjects enrolled

Romania: 21

Country: Number of subjects enrolled

Russian Federation: 87

Country: Number of subjects enrolled

Spain: 98

Country: Number of subjects enrolled

Switzerland: 13

Country: Number of subjects enrolled

Taiwan: 55

Country: Number of subjects enrolled

United States: 135

Country: Number of subjects enrolled

United Kingdom: 28

Worldwide total number of subjects

722

EEA total number of subjects

234

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)

719

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study is a Phase 3, randomized, double-blind, parallel group, non-inferiority study. The study consisted of double-blind phase, open-label phase and continuation phase.

Screening details

Total of 722 participants were enrolled and randomized; however only 719 participants (3 participants were never dosed following randomization) were dosed in to the study to receive either dolutegravir plus lamivudine (DTG+3TC) or dolutegravir plus tenofovir/emtricitabine (DTG+TDF/FTC) creating the intent to treat-exposed (ITT-E) Population.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

DTG + 3TC

Arm description

Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 96 weeks in a double-blind phase; from Week 96 to Week 148 in an open-label phase; and from Week 148 to Week 280 in a continuation phase.

Arm type

Experimental

Investigational medicinal product name

Lamivudine (3TC)

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

3TC 300 mg capsule, oral administration, once daily.

Investigational medicinal product name

Dolutegravir (DTG)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

DTG 50 mg tablet, oral administration, once daily.

DTG + TDF/FTC

Arm description

Participants received a three-drug regimen of DTG + TDF/FTC fixed dose combination (FDC) administered orally, once daily for 96 weeks in a double-blind phase and from Week 96 to Week 148 in an open-label phase.

Arm type

Active comparator

Investigational medicinal product name

Tenofovir disoproxil fumarate/emtricitabine fixed-dose combination (TDF/FTC)

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

300 mg TDF/ 200 mg FTC capsule, oral administration, once daily.

Investigational medicinal product name

Dolutegravir (DTG)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

DTG 50 mg tablet, oral administration, once daily.

Number of subjects in period 1 ^[1]	DTG + 3TC	DTG + TDF/FTC
Started	360	359
Completed	288	297
Not completed	72	62
Adverse event, serious fatal	2	1
Consent withdrawn by subject	21	18
Physician decision	9	6
Randomized, but did not receive treatment	-	3
Adverse event, non-fatal	9	11
Protocol Deviation	8	5
Protocol specific withdrawal criteria	1	2
Lost to follow-up	15	14
Lack of efficacy	7	2

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: A total of 722 participants were randomized to receive DTG+3TC and DTG+TDF/FTC. Three participants from DTG+TDF/FTC were randomized, but did not receive treatment. A total of 719 participants received treatment and were included in Intent-to-Treat Exposed (ITT-E) Population.

Baseline characteristics

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Reporting group title

Overall Study

Reporting group description

Reporting group values	Overall Study	Total
Number of subjects	719
Age categorical
Baseline Characteristic data are reported for the Intent-to-Treat Exposed (ITT-E) Population consisted of all randomized participants who received at least one dose of study medication.
Units: Participants
Age Continuous
Baseline Characteristic data are reported for the Intent-to-Treat Exposed (ITT-E) Population consisted of all randomized participants who received at least one dose of study medication.
Units: years
arithmetic mean (standard deviation)	34.5 ( 10.53 )	-
Sex: Female, Male
Baseline Characteristic data are reported for the Intent-to-Treat Exposed (ITT-E) Population consisted of all randomized participants who received at least one dose of study medication.
Units: Participants
Female	100	100
Male	619	619
Race/Ethnicity, Customized
Baseline Characteristic data are reported for the Intent-to-Treat Exposed (ITT-E) Population consisted of all randomized participants who received at least one dose of study medication.
Units: Subjects
American (Am) Indian or Alaska (Al.) native	45	45
Asian-Central/South Asian heritage (H.)	3	3
Asian - East Asian H.	54	54
Asian - South East Asian H.	7	7
Black or African Am	95	95
Native Hawaiian or other Pacific Islander	5	5
White (Wt)-Arabic/North African H.	6	6
Wt-Wt/Caucasian (Ca.)/European (Eu.) H.	480	480
Am Indian or Al. native and Wt	22	22
Black or African Am and Wt	2	2

End points

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Reporting group title

DTG + 3TC

Reporting group description

Reporting group title

DTG + TDF/FTC

Reporting group description

Subject analysis set title

DTG + 3TC - Double-blind Phase + Open-label Phase

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received a two-drug regimen of DTG + 3TC administered orally, once daily until Week 96 in double-blind phase and participants continued to receive DTG + 3TC from Week 96 to Week 148 in an open-label phase.

Subject analysis set title

DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily until Week 96 in double-blind phase and participants continued to receive DTG + TDF/FTC FDC from Week 96 to Week 148 in an open-label phase.

Subject analysis set title

DTG + 3TC - Double-blind Phase + Open-label Phase

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG + 3TC - Double-blind Phase + Open-label Phase

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Subject analysis set type

Sub-group analysis

Subject analysis set description

Primary: Percentage of participants with plasma Human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL (c/mL) at Week 48

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End point title

Percentage of participants with plasma Human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL (c/mL) at Week 48

End point description

Percentage of participants with HIV-1 RNA<50 c/mL was obtained using Food and Drug Administration (FDA) Snapshot algorithm. 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. This endpoint was analyzed using a stratified analysis with Cochran-Mantel-Haenszel (CMH) weights. Intent-To-Treat Exposed (ITT-E) Population was used which comprised of all randomized participants who received at least one dose of study treatment. Percentage values are rounded off.

End point type

Primary

End point timeframe

Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[1]	359 ^[2]
Units: Percentage of participants
number (confidence interval 95%)	93 (90.4 to 95.7)	94 (91.4 to 96.4)

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

Statistical Analysis

Statistical analysis description

Difference in proportion was based on CMH stratified analysis adjusting for Baseline stratification factors: Plasma HIV-1 RNA (<= vs. >100,000 copies per milliliter) and CD4+ cell count (<= vs. >200 cells per cubic millimeter [cells/mm^3]).

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Adjusted difference in proportion

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.3

upper limit

2.9

Notes
[3] - Treatment with DTG+ 3TC was to be declared non-inferior to treatment with DTG+TDF/FTC if the lower end of a two-sided 95% confidence interval for the difference between the two groups in response rates at Week 48 was greater than -10%.

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

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End point title

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

End point description

Percentage of participants with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. 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. This endpoint was analyzed using a stratified analysis with CMH weights. Percentage values are rounded off.

End point type

Secondary

End point timeframe

Week 24

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[4]	359 ^[5]
Units: Percentage of participants
number (confidence interval 95%)	94 (91.4 to 96.4)	94 (91.4 to 96.4)

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

Statistical Analysis

Statistical analysis description

Difference in proportion was based on CMH stratified analysis adjusting for Baseline stratification factors: Plasma HIV-1 RNA (<= vs. >100,000 c/mL) and CD4+ cell count (<= vs. >200 cells/mm^3).

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

Method

Parameter type

Adjusted difference in proportion

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.6

Notes
[6] - Treatment with DTG+ 3TC was to be declared non-inferior to treatment with DTG+TDF/FTC if the lower end of a two-sided 95% confidence interval for the difference between the two groups in response rates at Week 24 was greater than -10%.

Secondary: Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 96

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End point title

Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 96

End point description

End point type

Secondary

End point timeframe

Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[7]	359 ^[8]
Units: Percentage of participants
number (confidence interval 95%)	88 (84.4 to 91.2)	90 (86.5 to 92.8)

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

Statistical Analysis

Statistical analysis description

Week 96. Difference in proportion was based on CMH stratified analysis adjusting for Baseline stratification factors: Plasma HIV-1 RNA (<= vs. >100,000 c/mL) and CD4+ cell count (<= vs. >200 cells/mm^3).

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Adjusted difference in proportion

Point estimate

-1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-6.4

upper limit

2.7

Secondary: Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 144

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End point title

Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 144

End point description

End point type

Secondary

End point timeframe

Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[9]	359 ^[10]
Units: Percentage of participants
number (confidence interval 95%)	84 (80.4 to 87.9)	84 (80.6 to 88.2)

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

Statistical Analysis

Statistical analysis description

Week 144. Difference in proportion was based on CMH stratified analysis adjusting for Baseline stratification factors: Plasma HIV-1 RNA (<= vs. >100,000 c/mL) and CD4+ cell count (<= vs. >200 cells/mm^3).

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Adjusted difference in proportion

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-5.3

upper limit

5.3

Secondary: Time to Viral Suppression (HIV-1 RNA <50 c/mL) up to Week 144

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End point title

Time to Viral Suppression (HIV-1 RNA <50 c/mL) up to Week 144

End point description

Time of viral suppression is defined as the first viral load value <50 c/mL. Nonparametric Kaplan-Meier method was performed. Participants who withdrew for any reason without being suppressed were censored at date of withdrawal. Participants who have not been withdrawn and have not had viral suppression at time of the analysis were censored at last viral load date. Confidence Interval (CI) was estimated using the Brookmeyer-Crowley method.

End point type

Secondary

End point timeframe

Up to Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[11]	359 ^[12]
Units: Days
median (inter-quartile range (Q1-Q3))	29.0 (29.0 to 55.0)	29.0 (29.0 to 57.0)

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

Statistical Analysis

Statistical analysis description

Hazard ratios were estimated using the Cox proportional hazard regression model.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other ^[13]

P-value

= 0.797

Method

Generalised Wilcoxon procedure

Parameter type

Hazard ratio (HR)

Point estimate

1.02

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.19

Notes
[13] - The generalised Wilcoxon procedure was used to estimate a p-value for detecting a difference in cumulative incidence curves between treatment groups.

Secondary: CD4+ cell counts at Weeks 24 and 48

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End point title

CD4+ cell counts 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+ cells. Analysis was performed by flow cytometry. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Weeks 24 and 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[14]	359 ^[15]
Units: Cells/mm^3
arithmetic mean (standard deviation)
Week 24, n=349,345	650.4 ( 257.02 )	633.0 ( 287.37 )
Week 48, n=337,340	688.1 ( 266.39 )	689.8 ( 308.49 )

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

No statistical analyses for this end point

Secondary: CD4+ Cell Counts at Week 96

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End point title

CD4+ Cell Counts at Week 96

End point description

End point type

Secondary

End point timeframe

Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	318 ^[16]	327 ^[17]
Units: Cells/mm^3
arithmetic mean (standard deviation)	734.9 ( 270.82 )	739.9 ( 299.80 )

Notes
[16] - ITT-E Population
[17] - ITT-E Population

No statistical analyses for this end point

Secondary: CD4+ Cell Counts at Week 144

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End point title

CD4+ Cell Counts at Week 144

End point description

End point type

Secondary

End point timeframe

Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	296 ^[18]	292 ^[19]
Units: Cells/mm^3
arithmetic mean (standard deviation)	763.8 ( 266.61 )	770.4 ( 332.65 )

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

No statistical analyses for this end point

Secondary: Changes from Baseline in CD4+ cell counts at Week 24 and 48

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End point title

Changes from Baseline in CD4+ cell counts at Week 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+ cells. Analysis was performed by flow cytometry. Baseline value is defined as the the latest pre-dose assessment. Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted least mean and standard error has been presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for the following covariates/factors: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction, and Baseline CD4+ cell count and visit interaction, with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[20]	359 ^[21]
Units: Cells/mm^3
least squares mean (standard error)
Week 24, n=349, 345	188.8 ( 8.77 )	163.2 ( 9.08 )
Week 48, n=337, 340	225.7 ( 8.94 )	217.2 ( 9.93 )

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

Statistical Analysis 1

Statistical analysis description

Week 24. Following covariates/factors were adjusted: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction and Baseline CD4+ cell count and visit interaction with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.043

Method

Mixed Model Repeated Measures (MMRM)

Parameter type

Mean difference (net)

Point estimate

25.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

50.4

Statistical Analysis 2

Statistical analysis description

Week 48. Following covariates/factors were adjusted: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction and Baseline CD4+ cell count and visit interaction with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.523

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

8.5

Confidence interval

level

95%

sides

2-sided

lower limit

-17.7

upper limit

34.8

Secondary: Changes From Baseline in CD4+ Cell Counts at Week 96

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End point title

Changes From Baseline in CD4+ Cell Counts at Week 96

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+ cells. Analysis was performed by flow cytometry. Baseline value is defined as the the latest pre-dose assessment. Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for the following covariates/factors: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction, and Baseline CD4+ cell count and visit interaction, with visit as the repeated factor. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	318 ^[22]	327 ^[23]
Units: Cells/mm^3
arithmetic mean (standard error)	272.0 ( 10.83 )	264.6 ( 11.18 )

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

Statistical Analysis

Statistical analysis description

Week 96. Following covariates/factors were adjusted: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction and Baseline CD4+ cell count and visit interaction with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

645

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.635

Method

Mixed Model Repeated Measures (MMRM)

Parameter type

Mean difference (net)

Point estimate

7.4

Confidence interval

level

95%

sides

2-sided

lower limit

-23.2

upper limit

Secondary: Changes From Baseline in CD4+ Cell Counts at Week 144

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End point title

Changes From Baseline in CD4+ Cell Counts at Week 144

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+ cells. Analysis was performed by flow cytometry. Baseline value is defined as the the latest pre-dose assessment. Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for the following covariates/factors: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction, and Baseline CD4+ cell count and visit interaction, with visit as the repeated factor. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline and Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	296 ^[24]	292 ^[25]
Units: Cells/mm^3
arithmetic mean (standard error)	301.7 ( 11.55 )	296.6 ( 13.55 )

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

Statistical Analysis

Statistical analysis description

Week 144.Following covariates/factors were adjusted: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction and Baseline CD4+ cell count and visit interaction with visit as the repeated factor.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

588

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.777

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

5.1

Confidence interval

level

95%

sides

2-sided

lower limit

-29.9

upper limit

Secondary: Number of Participants With HIV-1 Disease Progression up to Week 144

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End point title

Number of Participants With HIV-1 Disease Progression up to Week 144

End point description

HIV-associated conditions were recorded during the study and was assessed according to the 2014 Centers for Disease Control and Prevention (CDC) Classification System for HIV Infection in Adults. Disease progressions 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 enrolment to Stage 3 event; CDC Category Stage 3 at enrollment to New Stage 3 Event; CDC Category Stage 1, 2 or 3 at enrolment to Death. Participants may have more than one indicators of clinical disease progression including death, hence they may contribute to data in more than one categories.

End point type

Secondary

End point timeframe

Up to Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[26]	359 ^[27]
Units: Participants
No disease progression	356	357
From CDC Stage 1 to CDC Stage 3 Event	0	0
From CDC Stage 2 to CDC Stage 3 Event	2	1
From CDC Stage 3 to New CDC Stage 3 Event	1	0
From CDC Stage 1, 2 or 3 to Death	2	1

Notes
[26] - ITT-E Population
[27] - ITT-E Population

No statistical analyses for this end point

Secondary: Number of Participants With Treatment-emergent Genotypic Resistance up to Week 144

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End point title

Number of Participants With Treatment-emergent Genotypic Resistance up to Week 144

End point description

Number of participants, who met confirmed virologic withdrawal (CVW) criteria, with treatment emergent genotypic resistance to Integrase strand transfer inhibitor (INSTI) and/or Nucleoside reverse transcriptase inhibitor (NRTI) was summarized. The Viral Genotypic Population comprised of all participants in the ITT-E population who have available on-treatment genotypic resistance data. Only those participants available at the specified time points were analyzed. The Viral Genotypic Population comprised of all participants in the ITT-E population who have available on-treatment genotypic resistance data.

End point type

Secondary

End point timeframe

Up to Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	7 ^[28]	3 ^[29]
Units: Participants
INSTI Mutations	0	0
Major mutations of the NRTI	0	0

Notes
[28] - Viral Genotypic Population.
[29] - Viral Genotypic Population.

No statistical analyses for this end point

Secondary: Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144

Top of page

End point title

Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144

End point description

Number of participants, who met CVW criteria, with treatment emergent phenotypic resistance to INSTI and/or NRTI were summarized. Assessment of antiviral activity of anti-retroviral therapy (ART) using phenotypic test results were interpreted through a proprietary algorithm (from Monogram Biosciences) and provides the overall susceptibility of the drugs (DTG, 3TC, Abacavir [ABC], elvitegravir [EGV], raltegravir [RAL], zidovudine [AZT], stavudine [D4T], didanosine [DDI]), emtricitabine [FTC], tenofovir disiproxil fumarate [TDF]). Partially sensitive and resistant cells were considered resistant in this analysis. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). The Viral Phenotypic Population comprised of all participants in the ITT-E population who have available on-treatment phenotypic resistance data.

End point type

Secondary

End point timeframe

Up to Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	7 ^[30]	4 ^[31]
Units: Participants
INSTI, DTG, Sensitive, n=7,2	7	2
INSTI, DTG, Resistant, n=7,2	0	0
INSTI, EGV, Sensitive, n=7,2	7	2
INSTI, EGV, Resistant, n=7,2	0	0
INSTI, RAL, Sensitive, n=7,2	7	2
INSTI, RAL, Resistant, n=7,2	0	0
NRTI, 3TC, Sensitive, n=7,3	7	3
NRTI, 3TC, Resistant, n=7,3	0	0
NRTI, ABC, Sensitive, n=7,3	7	3
NRTI, ABC, Resistant, n=7,3	0	0
NRTI, AZT, Sensitive, n=7,3	7	3
NRTI, AZT, Resistant, n=7,3	0	0
NRTI, D4T, Sensitive, n=7,3	7	3
NRTI, D4T, Resistant, n=7,3	0	0
NRTI, DDI, Sensitive, n=7,3	7	3
NRTI, DDI, Resistant, n=7,3	0	0
NRTI, FTC, Sensitive, n=7,3	7	3
NRTI, FTC, Resistant, n=7,3	0	0
NRTI, TDF, Sensitive, n=7,3	7	3
NRTI, TDF, Resistant, n=7,3	0	0

Notes
[30] - Viral Phenotypic Population.
[31] - Viral Phenotypic Population.

No statistical analyses for this end point

Secondary: Number of Participants With Any AE and SAE up to Week 148

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End point title

Number of Participants With Any AE and SAE up to Week 148

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. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or protocol-defined event associated with liver injury and impaired liver function were categorized as SAE.

End point type

Secondary

End point timeframe

Up to Week 148

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[32]	359 ^[33]
Units: Participants
Any AE	306	309
Any SAE	39	47

Notes
[32] - Safety Population
[33] - Safety Population

No statistical analyses for this end point

Secondary: Number of Participants With AEs by Maximum Severity Grades up to Week 148

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End point title

Number of Participants With AEs by Maximum Severity Grades up to Week 148

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. AEs 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 participants with adverse events by maximum grade have been presented.

End point type

Secondary

End point timeframe

Up to Week 148

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[34]	359 ^[35]
Units: Participants
Grade 1 AEs	54	54
Grade 2 AEs	211	205
Grade 3 AEs	32	43
Grade 4 AEs	7	6
Grade 5 AEs	2	1

Notes
[34] - Safety Population
[35] - Safety Population

No statistical analyses for this end point

Secondary: Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade up to Week 148

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End point title

Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade up to Week 148

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. AEs 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 participants with drug related AEs and drug related AEs by by maximum grade have been presented.

End point type

Secondary

End point timeframe

Up to Week 148

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[36]	359 ^[37]
Units: Participants
Any drug related AE	69	91
Drug related AEs with maximum toxicity Grade 1	37	53
Drug related AEs with maximum toxicity Grade 2	26	29
Drug related AEs with maximum toxicity Grade 3	5	8
Drug related AEs with maximum toxicity Grade 4	1	1
Drug related AEs with maximum toxicity Grade 5	0	0

Notes
[36] - Safety Population
[37] - 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 assessment of hemoglobin, leukocytes, neutrophils and platelet count. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 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 listed hematology parameters have been presented.

End point type

Secondary

End point timeframe

Up to Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[38]	359 ^[39]
Units: Participants
Hemoglobin, Grades 1 to 4	8	10
Hemoglobin, Grades 2 to 4	6	6
Hemoglobin, Grades 3 to 4	2	1
Hemoglobin, Grade 1	2	4
Hemoglobin, Grade 2	4	5
Hemoglobin, Grade 3	1	1
Hemoglobin, Grade 4	1	0
Leukocytes, Grades 1 to 4	5	5
Leukocytes, Grades 2 to 4	1	0
Leukocytes, Grades 3 to 4	0	0
Leukocytes, Grade 1	4	5
Leukocytes, Grade 2	1	0
Leukocytes, Grade 3	0	0
Leukocytes, Grade 4	0	0
Neutrophils, Grades 1 to 4	23	7
Neutrophils, Grades 2 to 4	8	3
Neutrophils, Grades 3 to 4	4	1
Neutrophils, Grade 1	15	4
Neutrophils, Grade 2	4	2
Neutrophils, Grade 3	2	1
Neutrophils, Grade 4	2	0
Platelets, Grades 1 to 4	13	9
Platelets, Grades 2 to 4	5	5
Platelets, Grades 3 to 4	0	0
Platelets, Grade 1	8	4
Platelets, Grade 2	5	5
Platelets, Grade 3	0	0
Platelets, Grade 4	0	0

Notes
[38] - Safety Population
[39] - Safety Population

No statistical analyses for this end point

Secondary: Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144

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End point title

Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144

End point description

Blood samples were collected up to Week 144 for assessment of Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (ALP), Aspartate aminotransferase (AST), Bilirubin, Carbon dioxide (CO2), Cholesterol, Creatine kinase (CK), Creatinine, Direct Bilirubin, Glomerular filtration rate (GFR), Hypercalcemia, Hyperglycemia, Hyperkalemia, Hypernatremia, Hypocalcemia, Hypoglycemia, Hypokalemia, Hyponatremia, Low density lipid (LDL) Cholesterol, Lactate Dehydrogenase, Lipase, Phosphate, and Triglycerides. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent chemistry toxicities in any of the chemistry parameters have been presented.

End point type

Secondary

End point timeframe

Up to Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[40]	359 ^[41]
Units: Participants
ALT, Grades 1 to 4	77	71
ALT, Grades 2 to 4	30	29
ALT, Grades 3 to 4	13	15
ALT, Grade 1	47	42
ALT, Grade 2	17	14
ALT, Grade 3	6	8
ALT, Grade 4	7	7
Albumin, Grades 1 to 4	2	1
Albumin, Grades 2 to 4	2	1
Albumin, Grades 3 to 4	0	1
Albumin, Grade 1	0	0
Albumin, Grade 2	2	0
Albumin, Grade 3	0	1
Albumin, Grade 4	0	0
ALP, Grades 1 to 4	10	17
ALP, Grades 2 to 4	2	3
ALP, Grades 3 to 4	0	1
ALP, Grade 1	8	14
ALP, Grade 2	2	2
ALP, Grade 3	0	1
ALP, Grade 4	0	0
AST, Grades 1 to 4	71	83
AST, Grades 2 to 4	30	32
AST, Grades 3 to 4	15	14
AST, Grade 1	41	51
AST, Grade 2	15	18
AST, Grade 3	8	11
AST, Grade 4	7	3
Bilirubin, Grades 1 to 4	46	56
Bilirubin, Grades 2 to 4	13	16
Bilirubin, Grades 3 to 4	4	3
Bilirubin, Grade 1	33	40
Bilirubin, Grade 2	9	13
Bilirubin, Grade 3	0	2
Bilirubin, Grade 4	4	1
CO2, Grades 1 to 4	111	111
CO2, Grades 2 to 4	10	4
CO2, Grades 3 to 4	0	0
CO2, Grade 1	101	107
CO2, Grade 2	10	4
CO2, Grade 3	0	0
CO2, Grade 4	0	0
Cholesterol, Grades 1 to 4	98	50
Cholesterol, Grades 2 to 4	23	12
Cholesterol, Grades 3 to 4	1	0
Cholesterol, Grade 1	75	38
Cholesterol, Grade 2	22	12
Cholesterol, Grade 3	1	0
Cholesterol, Grade 4	0	0
CK, Grades 1 to 4	91	83
CK, Grades 2 to 4	49	47
CK, Grades 3 to 4	29	28
CK, Grade 1	42	36
CK, Grade 2	20	19
CK, Grade 3	11	11
CK, Grade 4	18	17
Creatinine, Grades 1 to 4	18	28
Creatinine, Grades 2 to 4	5	2
Creatinine, Grades 3 to 4	0	1
Creatinine, Grade 1	13	26
Creatinine, Grade 2	5	1
Creatinine, Grade 3	0	1
Creatinine, Grade 4	0	0
Direct Bilirubin, Grades 1 to 4	11	10
Direct Bilirubin, Grades 2 to 4	11	10
Direct Bilirubin, Grades 3 to 4	11	10
Direct Bilirubin, Grade 1	0	0
Direct Bilirubin, Grade 2	0	0
Direct Bilirubin, Grade 3	11	10
Direct Bilirubin, Grade 4	0	0
GFR, Grades 1 to 4	198	219
GFR, Grades 2 to 4	198	219
GFR, Grades 3 to 4	20	29
GFR, Grade 1	0	0
GFR, Grade 2	178	190
GFR, Grade 3	20	28
GFR, Grade 4	0	1
Hypercalcaemia, Grades 1 to 4	4	5
Hypercalcaemia, Grades 2 to 4	0	1
Hypercalcaemia, Grades 3 to 4	0	1
Hypercalcemia, Grade 1	4	4
Hypercalcaemia, Grade 2	0	0
Hypercalcaemia, Grade 3	0	0
Hypercalcaemia, Grade 4	0	1
Hyperglycaemia, Grades 1 to 4	106	86
Hyperglycaemia, Grades 2 to 4	49	38
Hyperglycaemia, Grades 3 to 4	3	3
Hyperglycaemia, Grade 1	57	48
Hyperglycaemia, Grade 2	46	35
Hyperglycaemia, Grade 3	2	2
Hyperglycaemia, Grade 4	1	1
Hyperkalemia, Grades 1 to 4	7	7
Hyperkalemia, Grades 2 to 4	2	1
Hyperkalemia, Grades 3 to 4	1	1
Hyperkalemia, Grade 1	5	6
Hyperkalemia, Grade 2	1	0
Hyperkalemia, Grade 3	0	1
Hyperkalemia, Grade 4	1	0
Hypernatremia, Grades 1 to 4	4	7
Hypernatremia, Grades 2 to 4	1	0
Hypernatremia, Grades 3 to 4	0	0
Hypernatremia, Grade 1	3	7
Hypernatremia, Grade 2	1	0
Hypernatremia, Grade 3	0	0
Hypernatremia, Grade 4	0	0
Hypocalcaemia, Grades 1 to 4	17	21
Hypocalcaemia, Grades 2 to 4	6	11
Hypocalcaemia, Grades 3 to 4	1	3
Hypocalcaemia, Grade 1	11	10
Hypocalcaemia, Grade 2	5	8
Hypocalcaemia, Grade 3	1	2
Hypocalcaemia, Grade 4	0	1
Hypoglycaemia, Grades 1 to 4	22	21
Hypoglycaemia, Grades 2 to 4	6	5
Hypoglycaemia, Grades 3 to 4	4	1
Hypoglycaemia, Grade 1	16	16
Hypoglycaemia, Grade 2	2	4
Hypoglycaemia, Grade 3	3	0
Hypoglycaemia, Grade 4	1	1
Hypokalemia, Grades 1 to 4	9	5
Hypokalemia, Grades 2 to 4	0	1
Hypokalemia, Grades 3 to 4	0	0
Hypokalemia, Grade 1	9	4
Hypokalemia, Grade 2	0	1
Hypokalemia, Grade 3	0	0
Hypokalemia, Grade 4	0	0
Hyponatremia, Grades 1 to 4	23	22
Hyponatremia, Grades 2 to 4	0	3
Hyponatremia, Grades 3 to 4	0	1
Hyponatremia, Grade 1	23	19
Hyponatremia, Grade 2	0	2
Hyponatremia, Grade 3	0	0
Hyponatremia, Grade 4	0	1
LDL Cholesterol, Grades 1 to 4	66	40
LDL Cholesterol, Grades 2 to 4	21	13
LDL Cholesterol, Grades 3 to 4	6	2
LDL Cholesterol, Grade 1	45	27
LDL Cholesterol, Grade 2	15	11
LDL Cholesterol, Grade 3	6	2
LDL Cholesterol, Grade 4	0	0
Lactate Dehydrogenase, Grades 1 to 4	4	2
Lactate Dehydrogenase, Grades 2 to 4	3	0
Lactate Dehydrogenase, Grades 3 to 4	0	0
Lactate Dehydrogenase, Grade 1	1	2
Lactate Dehydrogenase, Grade 2	3	0
Lactate Dehydrogenase, Grade 3	0	0
Lactate Dehydrogenase, Grade 4	0	0
Lipase, Grades 1 to 4	72	81
Lipase, Grades 2 to 4	37	43
Lipase, Grades 3 to 4	9	17
Lipase, Grade 1	35	38
Lipase, Grade 2	28	26
Lipase, Grade 3	6	13
Lipase, Grade 4	3	4
Phosphate, Grades 1 to 4	75	78
Phosphate, Grades 2 to 4	50	51
Phosphate, Grades 3 to 4	7	7
Phosphate, Grade 1	25	27
Phosphate, Grade 2	43	44
Phosphate, Grade 3	7	7
Phosphate, Grade 4	0	0
Triglycerides, Grades 1 to 4	89	75
Triglycerides, Grades 2 to 4	22	15
Triglycerides, Grades 3 to 4	4	1
Triglycerides, Grade 1	67	60
Triglycerides, Grade 2	18	14
Triglycerides, Grade 3	4	1
Triglycerides, Grade 4	0	0

Notes
[40] - Safety Population
[41] - Safety Population

No statistical analyses for this end point

Secondary: Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48, 96

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End point title

Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48, 96

End point description

End point type

Secondary

End point timeframe

Up to Weeks 24, 48 and 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[42]	359 ^[43]
Units: Participants
Week 24	6	4
Week 48	8	8
Week 96	10	12

Notes
[42] - Safety Population
[43] - Safety Population

No statistical analyses for this end point

Secondary: Number of Participants Who Discontinue Treatment Due to AEs Over Week 144

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End point title

Number of Participants Who Discontinue Treatment Due to AEs Over Week 144

End point description

End point type

Secondary

End point timeframe

Up to Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[44]	359 ^[45]
Units: Participants	13	16

Notes
[44] - Safety Population
[45] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in renal biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48

Top of page

End point title

Change from Baseline in renal biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48

End point description

Blood and/or urine samples were collected to perform evaluation of renal biomarkers which included Serum Cystatin C and Serum RBP. Baseline value is the latest pre-dose assessment. Change from Baseline was defined as value at indicated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline and at Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[46]	359 ^[47]
Units: Milligrams per Liter (mg/L)
least squares mean (standard error)
Serum Cystatin C, Week 24, n=345,345	-0.04 ( 0.005 )	0.00 ( 0.005 )
Serum Cystatin C, Week 48, n=335,336	-0.05 ( 0.005 )	-0.04 ( 0.006 )
Serum RBP, Week 24, n=345,343	1.2 ( 0.42 )	1.4 ( 0.48 )
Serum RBP, Week 48, n=334, 334	0.6 ( 0.45 )	-0.1 ( 0.42 )

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

Statistical Analysis 1

Statistical analysis description

Week 24. Serum Cystatin C.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

-0.02

Statistical Analysis 3

Statistical analysis description

Week 24. Serum RBP

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.797

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

1.1

Statistical Analysis 4

Statistical analysis description

Week 48. Serum RBP

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.258

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

1.9

Statistical Analysis 2

Statistical analysis description

Week 48. Serum Cystatin C.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.022

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

Secondary: Change From Baseline in Renal Biomarker-Serum Cystatin C at Week 96

Top of page

End point title

Change From Baseline in Renal Biomarker-Serum Cystatin C at Week 96

End point description

Blood and/or urine samples were collected to perform evaluation of renal biomarkers which included Serum Cystatin C. Baseline value is the latest pre-dose assessment. Change from Baseline was defined as value at indicated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Adjusted mean and standard error is presented. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	316 ^[48]	326 ^[49]
Units: mg/L
arithmetic mean (standard error)	-0.09 ( 0.006 )	-0.08 ( 0.005 )

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

Statistical Analysis

Statistical analysis description

Week 96. Serum Cystatin C.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

642

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.034

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

Secondary: Change From Baseline in Renal Biomarker-Serum Cystatin C at Week 144

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End point title

Change From Baseline in Renal Biomarker-Serum Cystatin C at Week 144

End point description

End point type

Secondary

End point timeframe

Baseline and at Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	301 ^[50]	304 ^[51]
Units: mg/L
arithmetic mean (standard error)	-0.11 ( 0.005 )	-0.08 ( 0.006 )

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

Statistical Analysis

Statistical analysis description

Week 144. Serum Cystatin C.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

605

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.006

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04

upper limit

-0.01

Secondary: Change From Baseline in Renal Biomarker-Serum RBP at Week 96

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End point title

Change From Baseline in Renal Biomarker-Serum RBP at Week 96

End point description

Blood and/or urine samples were collected to perform evaluation of renal biomarkers which included Serum RBP. Baseline value is the latest pre-dose assessment. Change from Baseline was defined as value at indicated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	314 ^[52]	319 ^[53]
Units: Microgram per millimoles (ug/mmol)
arithmetic mean (standard deviation)	0.557 ( 12.7139 )	2.483 ( 23.9105 )

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

No statistical analyses for this end point

Secondary: Change From Baseline in Renal Biomarker-Serum RBP at Week 144

Top of page

End point title

Change From Baseline in Renal Biomarker-Serum RBP at Week 144

End point description

End point type

Secondary

End point timeframe

Baseline and at Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	294 ^[54]	289 ^[55]
Units: Microgram per millimoles (ug/mmol)
arithmetic mean (standard deviation)	0.560 ( 9.5962 )	3.813 ( 10.8115 )

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

No statistical analyses for this end point

Secondary: Change from Baseline in renal biomarkers-Serum GFR from cystatin C Adjusted using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR from creatinine adjusted using CKD-EPI at Weeks 24, 48

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End point title

Change from Baseline in renal biomarkers-Serum GFR from cystatin C Adjusted using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR from creatinine adjusted using CKD-EPI at Weeks 24, 48

End point description

Blood samples were collected to perform evaluation of renal biomarkers which included Serum GFR from cystatin C adjusted using CKD-EPI (GFR-cystatin C adjusted) and Serum or Plasma GFR from creatinine adjusted using CKD-EPI. Baseline value is the latest pre-dose Assessment. Change from Baseline was defined as value at the indicated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline and at Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[56]	359 ^[57]
Units: Milliliter/minute/1.73 meter^2
arithmetic mean (standard error)
GFR Cystatin C adjusted, Week 24, n=345,345	3.8 ( 0.66 )	0.2 ( 0.65 )
GFR Cystatin C adjusted, Week 48, n=335,336	5.4 ( 0.64 )	3.6 ( 0.64 )
GFR creatinine adjusted, Week 24, n=346,344	-12.0 ( 0.64 )	-15.4 ( 0.59 )
GFR creatinine adjusted, Week 48, n=335, 337	-12.1 ( 0.60 )	-15.4 ( 0.61 )

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

Statistical Analysis 1

Statistical analysis description

Week 24. GFR Cystatin C adjusted.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.8

upper limit

5.4

Statistical Analysis 3

Statistical analysis description

Week 24. GFR creatinine adjusted.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.7

upper limit

5.2

Statistical Analysis 4

Statistical analysis description

Week 48. GFR creatinine adjusted.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

3.3

Confidence interval

level

95%

sides

2-sided

lower limit

1.6

upper limit

Statistical Analysis 2

Statistical analysis description

Week 48. GFR Cystatin C adjusted.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.056

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

3.5

Secondary: Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI method at Week 96

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End point title

Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI method at Week 96

End point description

Blood samples were collected to perform evaluation of renal biomarkers which included Serum GFR from cystatin C adjusted using CKD-EPI and Serum or Plasma GFR from creatinine adjusted for BSA using CKD-EPI. Baseline value is the latest pre-dose Assessment. Change from Baseline was defined as value at the indicated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline and at Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[58]	359 ^[59]
Units: Milliliter/minute/1.73 meter^2
arithmetic mean (standard deviation)
GFR Cystatin C adjusted, Week 96, n=316,326	9.1 ( 18.75 )	9.5 ( 13.95 )
GFR creatinine adjusted, Week 96, n=315,325	-14.2 ( 12.69 )	-17.5 ( 11.57 )

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

No statistical analyses for this end point

Secondary: Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI method at Week 144

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End point title

Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI method at Week 144

End point description

End point type

Secondary

End point timeframe

Baseline and at Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[60]	359 ^[61]
Units: Milliliter/minute/1.73 meter^2
arithmetic mean (standard deviation)
GFR Cystatin C adjusted, Week 144, n=301,304	10.3 ( 18.82 )	10.1 ( 15.50 )
GFR creatinine adjusted, Week 144, n=292,292	-15.5 ( 12.56 )	-18.2 ( 11.73 )

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

No statistical analyses for this end point

Secondary: Change from Baseline in renal biomarker-Serum or Plasma Creatinine at Weeks 24, 48

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End point title

Change from Baseline in renal biomarker-Serum or Plasma Creatinine at Weeks 24, 48

End point description

Blood and samples were collected to perform evaluation of renal biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the the latest pre-dose assessment. Change from Baseline was calculated as value at the inidcated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline and at Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[62]	359 ^[63]
Units: Micromoles per Liter (umol/L)
arithmetic mean (standard deviation)
Serum or Plasma Creatinine, Week 24, n=346, 344	10.51 ( 0.548 )	13.53 ( 0.507 )
Serum or Plasma Creatinine, Week 48, n=335, 337	10.32 ( 0.519 )	13.44 ( 0.540 )

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

Statistical Analysis 2

Statistical analysis description

Week 48. Serum or Plasma creatinine

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.12

Confidence interval

level

95%

sides

2-sided

lower limit

-4.59

upper limit

-1.65

Statistical Analysis 1

Statistical analysis description

Week 24. Serum or Plasma Creatinine

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.02

Confidence interval

level

95%

sides

2-sided

lower limit

-4.49

upper limit

-1.55

Secondary: Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Week 96

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End point title

Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Week 96

End point description

Blood and samples were collected to perform evaluation of renal biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the the latest pre-dose assessment. Change from Baseline was calculated as value at the inidcated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Adjusted mean and standard error has been presented. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	315 ^[64]	325 ^[65]
Units: Micromoles per Liter (umol/L)
arithmetic mean (standard error)	11.71 ( 0.563 )	14.75 ( 0.526 )

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

Statistical Analysis

Statistical analysis description

Week 96. Serum or Plasma creatinine

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

640

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.04

Confidence interval

level

95%

sides

2-sided

lower limit

-4.56

upper limit

-1.53

Secondary: Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Week 144

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End point title

Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Week 144

End point description

Blood and samples were collected to perform evaluation of renal biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the the latest pre-dose assessment. Change from Baseline was calculated as value at the inidcated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Adjusted mean and standard error has been presented. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline and at Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	292 ^[66]	292 ^[67]
Units: Micromoles per Liter (umol/L)
arithmetic mean (standard error)	12.28 ( 0.613 )	15.14 ( 0.583 )

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

Statistical Analysis

Statistical analysis description

Week 144. Serum or Plasma creatinine

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

584

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.86

Confidence interval

level

95%

sides

2-sided

lower limit

-4.52

upper limit

-1.19

Secondary: Ratio to Baseline in renal biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48

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End point title

Ratio to Baseline in renal biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48

End point description

Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers: Urine and Serum B2M, Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine. Baseline value was the latest pre-dose assessment. Change from Baseline was performed on log-transformed data. Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Geometric mean ratio and 95% CI of geometric mean ratio have been presented. Biomarkers were Adjusted for treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, loge transformed Baseline biomarker value, treatment and visit interaction, and loge transformed Baseline biomarker value and visit interaction; with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline and Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[68]	359 ^[69]
Units: Ratio
geometric mean (confidence interval 95%)
Serum B2M, Week 24, n=344,346	0.809 (0.794 to 0.824)	0.882 (0.867 to 0.898)
Serum B2M, Week 48, n=335,336	0.811 (0.796 to 0.827)	0.887 (0.871 to 0.904)
Urine B2M, Week 24, n=124,106	0.844 (0.755 to 0.944)	1.129 (0.974 to 1.309)
Urine B2M, Week 48, n=109, 103	0.917 (0.804 to 1.046)	1.323 (1.066 to 1.642)
Urine Albumin/Creatinine, Week 24, n=259, 251	0.907 (0.844 to 0.976)	1.021 (0.940 to 1.109)
Urine Albumin/Creatinine , Week 48, n=249, 240	0.911 (0.835 to 0.994)	0.971 (0.891 to 1.058)
Urine B2M/Urine Creatinine , Week 24, n=122, 104	0.880 (0.779 to 0.993)	1.126 (0.988 to 1.282)
Urine B2M/Urine Creatinine , Week 48, n=108, 103	0.969 (0.854 to 1.099)	1.307 (1.077 to 1.586)
Urine Phosphate, Week 24, n=343, 340	1.041 (0.955 to 1.134)	1.063 (0.978 to 1.157)
Urine Phosphate, Week 48, n=335, 332	1.121 (1.031 to 1.220)	1.056 (0.974 to 1.144)
Urine Protein/Creatinine, Week 24, n=263,279	0.818 (0.779 to 0.859)	0.991 (0.941 to 1.043)
Urine Protein/Creatinine , Week 48, n=259, 261	0.866 (0.818 to 0.917)	1.007 (0.954 to 1.062)
Urine RBP 4, Week 24, n=340, 338	0.656 (0.591 to 0.729)	0.824 (0.738 to 0.921)
Urine RBP 4, Week 48, n=333, 331	0.740 (0.666 to 0.822)	0.819 (0.730 to 0.919)
Urine RBP 4/Urine Creatinine, Week 24, n=338, 335	0.670 (0.614 to 0.730)	0.811 (0.741 to 0.888)
Urine RBP 4/Urine Creatinine, Week 48, n=331, 328	0.749 (0.689 to 0.814)	0.844 (0.774 to 0.920)

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

Statistical Analysis 1

Statistical analysis description

Week 24. Serum B2M.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.917

Confidence interval

level

95%

sides

2-sided

lower limit

0.893

upper limit

0.941

Statistical Analysis 3

Statistical analysis description

Week 24. Urine B2M.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.002

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.748

Confidence interval

level

95%

sides

2-sided

lower limit

0.621

upper limit

0.901

Statistical Analysis 2

Statistical analysis description

Week 48. Serum B2M.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.914

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

0.939

Statistical Analysis 7

Statistical analysis description

Week 24. Urine B2M/Urine Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.007

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.781

Confidence interval

level

95%

sides

2-sided

lower limit

0.654

upper limit

0.934

Statistical Analysis 6

Statistical analysis description

Week 48. Urine Albumin/Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.308

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.938

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.061

Statistical Analysis 5

Statistical analysis description

Week 24. Urine Albumin/Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.036

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.889

Confidence interval

level

95%

sides

2-sided

lower limit

0.796

upper limit

0.992

Statistical Analysis 4

Statistical analysis description

Week 48. Urine B2M.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.005

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.693

Confidence interval

level

95%

sides

2-sided

lower limit

0.538

upper limit

0.892

Statistical Analysis 8

Statistical analysis description

Week 48. Urine B2M/Urine Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.012

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.742

Confidence interval

level

95%

sides

2-sided

lower limit

0.588

upper limit

0.935

Statistical Analysis 13

Statistical analysis description

Week 24. Urine RBP 4

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.003

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.796

Confidence interval

level

95%

sides

2-sided

lower limit

0.683

upper limit

0.927

Statistical Analysis 12

Statistical analysis description

Week 48. Urine Protein/Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.795

upper limit

0.93

Statistical Analysis 9

Statistical analysis description

Week 24. Urine Phosphate.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.728

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.979

Confidence interval

level

95%

sides

2-sided

lower limit

0.868

upper limit

1.104

Statistical Analysis 10

Statistical analysis description

Week 48. Urine Phosphate.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.311

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

1.062

Confidence interval

level

95%

sides

2-sided

lower limit

0.945

upper limit

1.194

Statistical Analysis 11

Statistical analysis description

Week 24. Urine Protein/Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.826

Confidence interval

level

95%

sides

2-sided

lower limit

0.769

upper limit

0.887

Statistical Analysis 14

Statistical analysis description

Week 48. Urine RBP 4

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.903

Confidence interval

level

95%

sides

2-sided

lower limit

0.773

upper limit

1.056

Statistical Analysis 15

Statistical analysis description

Week 24. Urine RBP 4/Urine Creatinine

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.003

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.826

Confidence interval

level

95%

sides

2-sided

lower limit

0.728

upper limit

0.936

Statistical Analysis 16

Statistical analysis description

Week 48. Urine RBP 4/Urine Creatinine

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.052

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.888

Confidence interval

level

95%

sides

2-sided

lower limit

0.787

upper limit

1.001

Secondary: Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 96

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End point title

Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 96

End point description

Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers: Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine. Baseline value was the latest pre-dose assessment. Change from Baseline was performed on log-transformed data. Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Biomarkers were Adjusted for treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, loge transformed Baseline biomarker value, treatment and visit interaction, and loge transformed Baseline biomarker value and visit interaction; with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline and Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[70]	359 ^[71]
Units: Ratio
geometric mean (confidence interval 95%)
Urine Albumin/Creatinine, Week 96, n=239, 243	0.939 (0.861 to 1.023)	0.997 (0.914 to 1.087)
Urine B2M/Urine Creatinine, Week 96, n=101, 96	0.844 (0.757 to 0.941)	1.259 (1.055 to 1.503)
Urine Phosphate, Week 96, n=316, 322	1.156 (1.064 to 1.256)	1.069 (0.988 to 1.156)
Urine Protein/Creatinine, Week 96, n=251, 261	0.887 (0.836 to 0.942)	1.016 (0.963 to 1.072)
Urine RBP 4/Urine Creatinine, Week 96, n=314, 318	1.030 (0.953 to 1.113)	1.287 (1.189 to 1.393)

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

Statistical Analysis 1

Statistical analysis description

Week 96. Urine Albumin/Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.338

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.942

Confidence interval

level

95%

sides

2-sided

lower limit

0.833

upper limit

1.065

Statistical Analysis 2

Statistical analysis description

Week 96. Urine B2M/Urine Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.671

Confidence interval

level

95%

sides

2-sided

lower limit

0.545

upper limit

0.826

Statistical Analysis 5

Statistical analysis description

Week 96. Urine RBP 4/Urine Creatinine

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.716

upper limit

0.894

Statistical Analysis 4

Statistical analysis description

Week 96. Urine Protein/Creatinine.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.873

Confidence interval

level

95%

sides

2-sided

lower limit

0.806

upper limit

0.946

Statistical Analysis 3

Statistical analysis description

Week 96. Urine Phosphate.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.174

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

1.082

Confidence interval

level

95%

sides

2-sided

lower limit

0.966

upper limit

1.213

Secondary: Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 144

Top of page

End point title

Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 144

End point description

End point type

Secondary

End point timeframe

Baseline and at Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[72]	359 ^[73]
Units: Ratio
geometric mean (confidence interval 95%)
Urine Albumin/Creatinine, Week 144, n=230, 221	1.036 (0.943 to 1.138)	1.067 (0.973 to 1.169)
Urine B2M/Urine Creatinine, Week 144, n=108, 93	0.872 (0.792 to 0.960)	1.494 (1.266 to 1.762)
Urine Phosphate, Week 144, n=301, 301	1.083 (1.000 to 1.174)	1.084 (0.999 to 1.175)
Urine Protein/Creatinine, Week 144, n=236, 246	0.999 (0.947 to 1.054)	1.180 (1.118 to 1.245)
Urine RBP 4/Urine Creatinine, Week 144, n=294, 289	1.159 (1.083 to 1.240)	1.567 (1.451 to 1.694)

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

Statistical Analysis 2

Statistical analysis description

Week 144. Urine B2M/Urine Creatinine.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.584

Confidence interval

level

95%

sides

2-sided

lower limit

0.483

upper limit

0.706

Statistical Analysis 1

Statistical analysis description

Week 144. Urine Albumin/Creatinine.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.658

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.971

Confidence interval

level

95%

sides

2-sided

lower limit

0.852

upper limit

1.107

Statistical Analysis 4

Statistical analysis description

Week 144. Urine Protein/Creatinine.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.847

Confidence interval

level

95%

sides

2-sided

lower limit

0.785

upper limit

0.913

Statistical Analysis 5

Statistical analysis description

Week 144. Urine RBP 4/Urine Creatinine

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

0.739

Confidence interval

level

95%

sides

2-sided

lower limit

0.667

upper limit

0.819

Statistical Analysis 3

Statistical analysis description

Week 144. Urine Phosphate.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.993

Method

MMRM

Parameter type

Ratio of geometric means

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.892

upper limit

1.12

Secondary: Change from Baseline in bone biomarkers-Serum Bone Specific Alkaline Phosphatase (bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48

Top of page

End point title

Change from Baseline in bone biomarkers-Serum Bone Specific Alkaline Phosphatase (bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48

End point description

Blood samples were collected to perform evaluation of bone biomarkers which included bone-ALP, Serum Osteocalcin, PINP and CTX-1. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as value at the indicated time point minus Baseline value. Only those participants available at the specified time 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, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[74]	359 ^[75]
Units: Micrograms per Liter (ug/L)
arithmetic mean (standard error)
Bone-ALP, Week 24, n=345, 346	0.72 ( 0.171 )	3.38 ( 0.244 )
Bone-ALP, Week 48, n=334, 337	1.24 ( 0.198 )	4.33 ( 0.268 )
Serum Osteocalcin, Week 24, n=345, 346	2.13 ( 0.321 )	6.80 ( 0.368 )
Serum Osteocalcin, Week 48, n=335, 336	0.40 ( 0.326 )	6.30 ( 0.384 )
PINP, Week 24, n=344, 346	1.7 ( 0.95 )	15.2 ( 1.12 )
PINP, Week 48, n=335, 337	0.4 ( 0.79 )	13.3 ( 1.06 )
CTX-1, Week 24, n=342, 342	0.1541 ( 0.01247 )	0.2812 ( 0.01406 )
CTX-1, Week 48, n=332, 333	0.1345 ( 0.01496 )	0.3388 ( 0.01983 )

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

Statistical Analysis 1

Statistical analysis description

Week 24, Bone ALP

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.66

Confidence interval

level

95%

sides

2-sided

lower limit

-3.25

upper limit

-2.08

Statistical Analysis 2

Statistical analysis description

Week 48, Bone ALP

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.09

Confidence interval

level

95%

sides

2-sided

lower limit

-3.75

upper limit

-2.44

Statistical Analysis 3

Statistical analysis description

Week 28, Serum Osteocalcin

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.67

Confidence interval

level

95%

sides

2-sided

lower limit

-5.63

upper limit

-3.71

Statistical Analysis 4

Statistical analysis description

Week 48, Serum Osteocalcin

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-5.9

Confidence interval

level

95%

sides

2-sided

lower limit

-6.89

upper limit

-4.91

Statistical Analysis 5

Statistical analysis description

Week 24, Serum PINP

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-13.5

Confidence interval

level

95%

sides

2-sided

lower limit

-16.4

upper limit

-10.6

Statistical Analysis 6

Statistical analysis description

Week 48, Serum PINP

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-12.8

Confidence interval

level

95%

sides

2-sided

lower limit

-15.4

upper limit

-10.2

Statistical Analysis 7

Statistical analysis description

Week 24, CTX-1

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.127

Confidence interval

level

95%

sides

2-sided

lower limit

-0.164

upper limit

-0.09

Statistical Analysis 8

Statistical analysis description

Week 48, CTX-1

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.2043

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2532

upper limit

-0.1554

Secondary: Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 96

Top of page

End point title

Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 96

End point description

Blood samples were collected to perform evaluation of bone biomarkers which included bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type CTX-1. Adjusted mean is the estimated mean change from Baseline in each arm calculated from a repeated measures model adjusting for: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current vitamin D use (factor), Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[76]	359 ^[77]
Units: Micrograms per Liter (ug/L)
arithmetic mean (standard error)
Bone-ALP, Week 96, n=315, 326	0.26 ( 0.188 )	2.39 ( 0.234 )
Serum Osteocalcin, Week 96, n=315, 326	0.13 ( 0.286 )	3.90 ( 0.368 )
PINP, Week 96, n=315, 325	7.0 ( 1.37 )	19.5 ( 1.66 )
CTX-1, Week 96, n=311, 318	0.0604 ( 0.01056 )	0.1787 ( 0.01403 )

Notes
[76] - Safety Population.
[77] - Safety Population.

Statistical Analysis 1

Statistical analysis description

Week 96, Bone ALP

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.13

Confidence interval

level

95%

sides

2-sided

lower limit

-2.72

upper limit

-1.54

Statistical Analysis 4

Statistical analysis description

Week 96, CTX-1

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.1183

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1529

upper limit

-0.0838

Statistical Analysis 3

Statistical analysis description

Week 96, Serum PINP

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-12.6

Confidence interval

level

95%

sides

2-sided

lower limit

-16.8

upper limit

-8.3

Statistical Analysis 2

Statistical analysis description

Week 96, Serum Osteocalcin

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.77

Confidence interval

level

95%

sides

2-sided

lower limit

-4.69

upper limit

-2.85

Secondary: Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 144

Top of page

End point title

Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 144

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[78]	359 ^[79]
Units: Micrograms per Liter (ug/L)
arithmetic mean (standard error)
Bone-ALP, Week 144, n=302, 305	-0.25 ( 0.156 )	1.88 ( 0.266 )
Serum Osteocalcin, Week 144, n=300, 304	-1.02 ( 0.280 )	2.87 ( 0.412 )
PINP, Week 144, n=299, 300	-0.1 ( 0.94 )	9.4 ( 1.39 )
CTX-1, Week 144, n=291, 298	0.0505 ( 0.01154 )	0.1868 ( 0.01516 )

Notes
[78] - Safety Population.
[79] - Safety Population.

Statistical Analysis 1

Statistical analysis description

Week 144, Bone ALP

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-2.13

Confidence interval

level

95%

sides

2-sided

lower limit

-2.74

upper limit

-1.53

Statistical Analysis 4

Statistical analysis description

Week 144, CTX-1

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.1364

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1739

upper limit

-0.0988

Statistical Analysis 3

Statistical analysis description

Week 144, Serum PINP

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-9.5

Confidence interval

level

95%

sides

2-sided

lower limit

-12.8

upper limit

-6.2

Statistical Analysis 2

Statistical analysis description

Week 144, Serum Osteocalcin

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3.89

Confidence interval

level

95%

sides

2-sided

lower limit

-4.87

upper limit

-2.91

Secondary: Change from Baseline in bone biomarker-Serum Vitamin D at Weeks 24, 48

Top of page

End point title

Change from Baseline in bone biomarker-Serum Vitamin D at Weeks 24, 48

End point description

Blood samples were collected to perform evaluation of bone biomarker serum vitamin D. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as value at the indicated time point minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline and at Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[80]	359 ^[81]
Units: Nanomoles per Liter (nmol/L)
least squares mean (standard error)
Serum Vitamin D, Week 24, n=346, 344	11.2 ( 1.08 )	15.4 ( 1.33 )
Serum Vitamin D, Week 48, n=336, 335	0.3 ( 0.92 )	0.4 ( 1.01 )

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

Statistical Analysis 2

Statistical analysis description

Week 48

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.96

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

2.6

Statistical Analysis 1

Statistical analysis description

Week 24

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.015

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-7.5

upper limit

-0.8

Secondary: Change From Baseline in Bone Biomarker-Serum Vitamin D at Week 96

Top of page

End point title

Change From Baseline in Bone Biomarker-Serum Vitamin D at Week 96

End point description

End point type

Secondary

End point timeframe

Baseline and at Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	312 ^[82]	326 ^[83]
Units: Nanomoles per Liter (nmol/L)
arithmetic mean (standard error)	-1.7 ( 1.01 )	1.3 ( 1.09 )

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

Statistical Analysis

Statistical analysis description

Week 96

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

638

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.048

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.9

upper limit

Secondary: Change From Baseline in Bone Biomarker-Serum Vitamin D at Week 144

Top of page

End point title

Change From Baseline in Bone Biomarker-Serum Vitamin D at Week 144

End point description

End point type

Secondary

End point timeframe

Baseline and at Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	303 ^[84]	303 ^[85]
Units: Nanomoles per Liter (nmol/L)
arithmetic mean (standard error)	1.1 ( 1.20 )	1.4 ( 1.22 )

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

Statistical Analysis

Statistical analysis description

Week 144

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

606

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.887

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-3.6

upper limit

3.1

Secondary: Percentage change from Baseline in fasting lipids-Serum or Plasma Cholesterol, Serum or Plasma High density lipoprotein (HDL) Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48

Top of page

End point title

Percentage change from Baseline in fasting lipids-Serum or Plasma Cholesterol, Serum or Plasma High density lipoprotein (HDL) Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48

End point description

Blood samples were collected to perform evaluation of fasting lipids which included Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides. Baseline value is defined as the latest pre-dose assessment (Day 1). Percentage change from Baseline was calculated as 100 multiplied by ([post-dose visit value minus Baseline value] divided by Baseline value). Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline and at Weeks 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[86]	359 ^[87]
Units: Percentage change
arithmetic mean (standard deviation)
Serum or Plasma Cholesterol, Week 24, n=298, 310	5.0 ( 16.85 )	-4.5 ( 15.44 )
Serum or Plasma Cholesterol, Week 48, n=298, 307	9.3 ( 17.10 )	-3.3 ( 14.61 )
HDL Cholesterol, Direct, Week 24, n=299, 310	13.9 ( 25.17 )	7.2 ( 32.22 )
HDL Cholesterol, Direct, Week 48, n=299, 307	15.3 ( 23.75 )	4.0 ( 21.86 )
LDL Cholesterol, Week 24, n=298, 309	3.8 ( 25.85 )	-7.8 ( 21.13 )
LDL Cholesterol, Week 48, n=297, 307	10.7 ( 27.54 )	-4.1 ( 20.39 )
Triglycerides,Week 24, n=299, 310	7.0 ( 40.45 )	0.5 ( 44.01 )
Triglycerides, Week 48, n=299, 307	7.3 ( 46.92 )	-0.3 ( 49.22 )

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

No statistical analyses for this end point

Secondary: Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Week 96

Top of page

End point title

Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Week 96

End point description

Blood samples were collected to perform evaluation of fasting lipids which included Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides. Baseline value was defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[88]	359 ^[89]
Units: Millimoles per liter
arithmetic mean (standard error)
Serum or Plasma Cholesterol, Week 96, n=270, 289	0.345 ( 0.0356 )	-0.132 ( 0.0375 )
HDL Cholesterol, Direct, Week 96, n=271, 289	0.185 ( 0.0160 )	0.071 ( 0.0136 )
LDL Cholesterol, Week 96, n=270, 289	0.139 ( 0.0308 )	-0.160 ( 0.0304 )
Triglycerides, Week 96, n=271, 289	0.105 ( 0.0488 )	-0.102 ( 0.0365 )

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

No statistical analyses for this end point

Secondary: Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Week 144

Top of page

End point title

End point description

Blood samples were collected to perform evaluation of fasting lipids which included Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides. Baseline value was defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[90]	359 ^[91]
Units: Millimoles per liter
arithmetic mean (standard error)
Serum or Plasma Cholesterol, Week 144, n=263, 278	0.360 ( 0.0432 )	-0.015 ( 0.0394 )
HDL Cholesterol, Direct, Week 144, n=264, 278	0.180 ( 0.0162 )	0.093 ( 0.0136 )
LDL Cholesterol, Week 144, n=263, 278	0.143 ( 0.0357 )	-0.085 ( 0.0333 )
Triglycerides, Week 144, n=264, 278	0.078 ( 0.0448 )	-0.057 ( 0.0430 )

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

No statistical analyses for this end point

Secondary: Percentage change from Baseline in fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48

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End point title

Percentage change from Baseline in fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48

End point description

Blood samples were collected to perform evaluation of fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio. Baseline value is the the latest pre-dose assessment (Day 1). Percentage change from Baseline was calculated as 100 multiplied by ([post-dose visit value minus Baseline value] divided by Baseline value). Lipid last observation carried forwarded (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values. Participants on lipid-lowering agents at Baseline were excluded. Only those participants available at the specified time 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, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[92]	359 ^[93]
Units: Percentage change
arithmetic mean (standard deviation)
Total/HDL Cholesterol Ratio, Week 24, n=298, 310	-4.4 ( 22.53 )	-7.5 ( 17.90 )
Total/HDL Cholesterol Ratio, Week 48, n=298, 307	-2.8 ( 17.86 )	-4.5 ( 18.25 )

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

No statistical analyses for this end point

Secondary: Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Week 96

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End point title

Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Week 96

End point description

Blood samples were collected to perform evaluation of fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio. Baseline value is the the latest pre-dose assessment (Day 1). Baseline value was defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	270 ^[94]	289 ^[95]
Units: Ratio
arithmetic mean (standard error)	-0.113 ( 0.1552 )	-0.395 ( 0.0473 )

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

No statistical analyses for this end point

Secondary: Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Week 144

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End point title

Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Week 144

End point description

Blood samples were collected to perform evaluation of fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio. Baseline value is the the latest pre-dose assessment (Day 1). Baseline value was defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	263 ^[96]	278 ^[97]
Units: Ratio
arithmetic mean (standard error)	-0.245 ( 0.0545 )	-0.359 ( 0.0533 )

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

No statistical analyses for this end point

Secondary: Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Weeks 24, 48

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End point title

Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Weeks 24, 48

End point description

Blood samples were collected to perform evaluation of fasting LDL cholesterol. Any abnormalities were evaluated by the investigator and graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Weeks 24 and 48 have been presented. Participants without any post-Baseline fasting LDL cholesterol value prior to Week 48 or those who had Baseline lipids-lowering agents were not included. Lipid Last Observation Carried Forward (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values. Percentage values are rounded-off. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Weeks 24 and 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[98]	359 ^[99]
Units: Percentage of participants
Week 24, n=313, 320	4	0
Week 48, n=324, 332	4	2

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

Statistical Analysis 2

Statistical analysis description

Week 48

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.037

Method

Fisher exact

Parameter type

Mean difference (final values)

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

5.4

Statistical Analysis 1

Statistical analysis description

Week 24

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Fisher exact

Parameter type

Mean difference (final values)

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

5.6

Secondary: Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Week 96

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End point title

Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Week 96

End point description

Blood samples were collected to perform evaluation of fasting LDL cholesterol. Any abnormalities were evaluated by the investigator and graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Week 96 have been presented. Participants without any post-Baseline fasting LDL cholesterol value prior to Week 96 or those who had Baseline lipids-lowering agents were not included. Lipid Last Observation Carried Forward (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values. Percentage values are rounded-off. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	324 ^[100]	332 ^[101]
Units: Percentage of participants	6	2

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

Statistical Analysis

Statistical analysis description

Week 96

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

656

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.045

Method

Fisher exact

Parameter type

Mean difference (final values)

Point estimate

3.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

6.1

Secondary: Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with plasma HIV-1 RNA <50 c/mL at Week 24

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End point title

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with plasma HIV-1 RNA <50 c/mL at Week 24

End point description

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. 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. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200 cells/mm^3, >200 cells/mm^3 for group-1), Baseline HIV-1 RNA (<=100000, >100000 c/mL) and Race (White, African American/African heritage (H.), Asian other). Percentage values are rounded-off. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Week 24

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[102]	359 ^[103]
Units: Percentage of participants
Baseline CD4+ cell count Group-1, <=200,n=32,26	78	92
Baseline CD4+ cell count Group-1, >200,n=328,333	95	94
Female, n=54, 46	93	89
Male, n=306, 313	94	95
Age, <35,n= 209, 203	93	94
Age, 35 to <50,n=115, 122	96	94
Age, >=50, n=36, 34	94	91
Baseline plasma HIV-1 RNA, <=100000,n=294,282	94	95
Baseline plasma HIV-1 RNA, >100000,n=66, 77	92	90
Race, White, n=237,249	95	95
Race, African American/African H., n=55, 40	89	90
Race, Asian, n=34, 30	97	90
Race, Other, n=34, 40	91	93

Notes
[102] - ITT-E Population.
[103] - ITT-E Population.

No statistical analyses for this end point

Secondary: Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Week 144

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End point title

Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Week 144

End point description

Blood samples were collected to perform evaluation of fasting LDL cholesterol. Any abnormalities were evaluated by the investigator and graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Week 144 have been presented. Participants without any post-Baseline fasting LDL cholesterol value prior to Week 144 or those who had Baseline lipids-lowering agents were not included. Lipid Last Observation Carried Forward (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values. Percentage values are rounded-off. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	324 ^[104]	333 ^[105]
Units: Percentage of participants	6	4

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

Statistical Analysis

Statistical analysis description

Week 144

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

657

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.16

Method

Fisher exact

Parameter type

Mean difference (final values)

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

Secondary: Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count Baseline HIV-1 RNA, race) with plasma HIV-1 RNA <50 c/mL at Week 48

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End point title

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count Baseline HIV-1 RNA, race) with plasma HIV-1 RNA <50 c/mL at Week 48

End point description

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. 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. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200 cells/mm^3, >200 cells/mm^3 for group-1), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian and other). Percentage values are rounded-off. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[106]	359 ^[107]
Units: Percentage of participants
Baseline CD4+ cell count Group-1, <=200,n=32, 26	78	96
Baseline CD4+ cell count Group-1, >200,n=328,333	95	94
Female, n=54, 46	89	87
Male, n=306, 313	94	95
Age, <35,n= 209,203	92	94
Age, 35 to <50,n=115, 122	97	94
Age, >=50, n=36, 34	89	94
Baseline plasma HIV-1 RNA, <=100000,n=294,282	92	95
Baseline plasma HIV-1 RNA, >100000,n=66, 77	97	90
Race, White, n=237,249	96	96
Race, African American/African H., n=55, 40	80	88
Race, Asian, n=34, 30	97	90
Race, Other, n=34, 40	88	90

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

No statistical analyses for this end point

Secondary: Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96

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End point title

Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96

End point description

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. 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. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200 cells/mm^3, >200 cells/mm^3), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian and other). Percentage values are rounded-off. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[108]	359 ^[109]
Units: Percentage of participants
Baseline CD4+ cell count, <=200,n=32, 26	72	85
Baseline CD4+ cell count, >200,n=328,333	89	90
Female, n=54, 46	81	85
Male, n=306, 313	89	90
Age, <35,n= 209, 203	88	91
Age, 35 to <50,n=115, 122	90	89
Age, >=50, n=36, 34	83	88
Baseline plasma HIV-1 RNA, <=100000,n=294, 282	88	91
Baseline plasma HIV-1 RNA, >100000,n=66, 77	86	84
Race, White, n=240,252	92	91
Race, African American/African H., n=51, 35	69	86
Race, Asian, n=34, 30	88	90
Race, Other, n=35, 42	89	83

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

No statistical analyses for this end point

Secondary: Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144

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End point title

Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144

End point description

Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. 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. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200 cells/mm^3, >200 cells/mm^3), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian and other). Percentage values are rounded-off. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[110]	359 ^[111]
Units: Percentage of participants
Baseline CD4+ cell count, <=200,n=32, 26	75	69
Baseline CD4+ cell count, >200,n=328,333	85	86
Female, n=54, 46	78	83
Male, n=306, 313	85	85
Age, <35,n= 209, 203	83	83
Age, 35 to <50,n=115, 122	86	85
Age, >=50, n=36, 34	83	88
Baseline plasma HIV-1 RNA, <=100000,n=294, 282	84	85
Baseline plasma HIV-1 RNA, >100000,n=66, 77	86	81
Race, White, n=240,252	88	87
Race, African American/African H., n=51, 35	65	74
Race, Asian, n=34, 30	85	83
Race, Other, n=35, 42	89	79

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

No statistical analyses for this end point

Secondary: Changes from Baseline in CD4+ cell counts at Week 24 by subgroups

Top of page

End point title

Changes from Baseline in CD4+ cell counts at Week 24 by subgroups

End point description

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, number of these cells declines. It was evaluated by flow cytometry. Baseline value is latest pre-dose assessment (Day 1). Change from Baseline was defined as value at indicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 24

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[112]	359 ^[113]
Units: Cells/mm^3
arithmetic mean (standard error)
Baseline plasma HIV-1 RNA,<=100000, n=283,273	186.01 ( 9.948 )	148.21 ( 10.134 )
Baseline plasma HIV-1 RNA,>100000, n=66,72	193.90 ( 20.811 )	220.71 ( 19.814 )
Baseline CD4+ cell count,<=200, n=29, 26	167.95 ( 31.308 )	106.23 ( 32.990 )
Baseline CD4+ cell count,>200, n=320, 319	189.91 ( 9.362 )	167.35 ( 9.362 )
Age group, <35,n= 201, 193	190.12 ( 11.829 )	151.13 ( 12.050 )
Age group-1, 35 to <50, n=113, 119	180.50 ( 15.733 )	190.40 ( 15.404 )
Age group-1, >=50, n=32, 32	198.74 ( 28.411 )	133.21 ( 29.120 )
Female, n=52, 42	213.58 ( 23.225 )	153.92 ( 25.910 )
Male, n=297, 303	183.41 ( 9.719 )	164.18 ( 9.631 )
Race group, White, n=233, 240	182.20 ( 10.987 )	168.30 ( 10.846 )
Race group, African Am/African H., n=51, 39	214.17 ( 23.472 )	145.44 ( 26.841 )
Race group, Asian, n=33, 28	154.14 ( 29.401 )	141.22 ( 31.663 )
Race group, Other, n=32, 38	222.24 ( 29.643 )	163.05 ( 27.293 )

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

Statistical Analysis 4

Statistical analysis description

Baseline CD4+ cell count,>200. Following covariates were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and Baseline CD4+ cell count interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

22.57

Confidence interval

level

95%

sides

2-sided

lower limit

-3.42

upper limit

48.55

Statistical Analysis 3

Statistical analysis description

Baseline CD4+ cell count,<=200. Following covariates were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and Baseline CD4+ cell count interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

61.72

Confidence interval

level

95%

sides

2-sided

lower limit

-26.94

upper limit

150.39

Statistical Analysis 2

Statistical analysis description

Baseline plasma HIV-1 RNA,>100000. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, Baseline plasma HIV-1 RNA, and treatment and Baseline plasma HIV-1 RNA interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-26.81

Confidence interval

level

95%

sides

2-sided

lower limit

-82.72

upper limit

29.1

Statistical Analysis 1

Statistical analysis description

Baseline plasma HIV-1 RNA,<=100000. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, Baseline plasma HIV-1 RNA, and treatment and relevant Baseline plasma HIV-1 RNA interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

37.8

Confidence interval

level

95%

sides

2-sided

lower limit

9.98

upper limit

65.62

Statistical Analysis 9

Statistical analysis description

Male. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

19.23

Confidence interval

level

95%

sides

2-sided

lower limit

-7.65

upper limit

46.1

Statistical Analysis 10

Statistical analysis description

Race group-white. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

13.9

Confidence interval

level

95%

sides

2-sided

lower limit

-16.35

upper limit

44.15

Statistical Analysis 11

Statistical analysis description

Race group-African Am/African H. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

68.74

Confidence interval

level

95%

sides

2-sided

lower limit

-1.24

upper limit

138.72

Statistical Analysis 12

Statistical analysis description

Race group-Asian. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

12.93

Confidence interval

level

95%

sides

2-sided

lower limit

-71.9

upper limit

97.75

Statistical Analysis 8

Statistical analysis description

Female. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

59.66

Confidence interval

level

95%

sides

2-sided

lower limit

-8.62

upper limit

127.94

Statistical Analysis 13

Statistical analysis description

Race group-Other. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

59.19

Confidence interval

level

95%

sides

2-sided

lower limit

-19.73

upper limit

138.11

Statistical Analysis 6

Statistical analysis description

Age Group,35 to <50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-9.9

Confidence interval

level

95%

sides

2-sided

lower limit

-53.1

upper limit

33.3

Statistical Analysis 5

Statistical analysis description

Age Group,<35. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

38.99

Confidence interval

level

95%

sides

2-sided

lower limit

5.88

upper limit

72.09

Statistical Analysis 7

Statistical analysis description

Age Group,>=50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

65.53

Confidence interval

level

95%

sides

2-sided

lower limit

-14.43

upper limit

145.5

Secondary: Changes from Baseline in CD4+ cell counts at Week 48 by subgroups

Top of page

End point title

Changes from Baseline in CD4+ cell counts at Week 48 by subgroups

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. It was evaluated by flow cytometry. Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from Analysis of Covariance (ANCOVA) model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[114]	359 ^[115]
Units: Cells/mm^3
least squares mean (standard error)
Baseline plasma HIV-1 RNA,<=100000, n=273,271	215.6 ( 10.67 )	208.7 ( 10.71 )
Baseline plasma HIV-1 RNA,>100000, n=64,69	261.8 ( 22.27 )	248.7 ( 21.30 )
Baseline CD4+ cell count,<=200, n=28, 25	210.9 ( 33.42 )	153.2 ( 35.29 )
Baseline CD4+ cell count,>200, n=309, 315	225.8 ( 10.00 )	221.7 ( 9.89 )
Age group-1, <35,n= 193, 191	234.2 ( 12.67 )	201.7 ( 12.72 )
Age group-1, 35 to <50, n=112, 117	212.7 ( 16.59 )	244.2 ( 16.31 )
Age group-1, >=50, n=32, 32	209.1 ( 31.20 )	203.9 ( 31.06 )
Age group-2, <50,n= 305, 308	226.4 ( 10.09 )	217.8 ( 10.03 )
Age group-2, >=50, n= 32, 32	208.5 ( 31.27 )	204.1 ( 31.14 )
Female, n=48, 41	236.2 ( 25.35 )	263.6 ( 27.50 )
Male, n=289, 299	222.8 ( 10.33 )	210.0 ( 10.17 )
Race group, White, n=227, 241	223.3 ( 11.70 )	214.2 ( 11.38 )
Race group, African Am/African H., n=45, 36	214.0 ( 26.25 )	233.7 ( 29.39 )
Race group, Asian, n=33, 27	205.0 ( 30.92 )	189.3 ( 33.90 )
Race group, Other, n=32, 36	270.2 ( 31.16 )	235.3 ( 29.47 )

Notes
[114] - ITT-E Population.
[115] - ITT-E Population.

Statistical Analysis 4

Statistical analysis description

Baseline CD4+ cell count,>200. Following covariates were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and Baseline CD4+ cell count interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-23.5

upper limit

31.7

Statistical Analysis 3

Statistical analysis description

Baseline CD4+ cell count,<=200. Following covariates were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and Baseline CD4+ cell count interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

57.7

Confidence interval

level

95%

sides

2-sided

lower limit

-37.2

upper limit

152.5

Statistical Analysis 2

Statistical analysis description

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

13.2

Confidence interval

level

95%

sides

2-sided

lower limit

-46.8

upper limit

73.2

Statistical Analysis 1

Statistical analysis description

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

6.9

Confidence interval

level

95%

sides

2-sided

lower limit

-22.7

upper limit

36.6

Statistical Analysis 9

Statistical analysis description

Male. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

12.8

Confidence interval

level

95%

sides

2-sided

lower limit

-15.7

upper limit

41.2

Statistical Analysis 10

Statistical analysis description

Race group-white. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

9.1

Confidence interval

level

95%

sides

2-sided

lower limit

-22.9

upper limit

41.1

Statistical Analysis 11

Statistical analysis description

Race group-African Am/African H. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-19.8

Confidence interval

level

95%

sides

2-sided

lower limit

-97.1

upper limit

57.6

Statistical Analysis 12

Statistical analysis description

Race group-Asian. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

15.7

Confidence interval

level

95%

sides

2-sided

lower limit

-74.4

upper limit

105.9

Statistical Analysis 8

Statistical analysis description

Female. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-27.3

Confidence interval

level

95%

sides

2-sided

lower limit

-100.8

upper limit

46.1

Statistical Analysis 13

Statistical analysis description

Race group-Other. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-49

upper limit

119

Statistical Analysis 6

Statistical analysis description

Age Group-1,35 to <50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-31.5

Confidence interval

level

95%

sides

2-sided

lower limit

-77.1

upper limit

14.2

Statistical Analysis 5

Statistical analysis description

Age Group-1,<35. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

32.5

Confidence interval

level

95%

sides

2-sided

lower limit

-2.7

upper limit

67.7

Statistical Analysis 7

Statistical analysis description

Age Group-1,>=50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

5.2

Confidence interval

level

95%

sides

2-sided

lower limit

-81.4

upper limit

91.8

Secondary: Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups

Top of page

End point title

Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups

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. It was evaluated by flow cytometry. Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[116]	359 ^[117]
Units: Cells/mm^3
arithmetic mean (standard error)
Baseline plasma HIV-1 RNA,<=100000, n=259,260	257.9 ( 12.47 )	257.5 ( 12.45 )
Baseline plasma HIV-1 RNA,>100000, n=59,67	312.1 ( 26.37 )	297.4 ( 24.59 )
Baseline CD4+ cell count,<=200, n=25, 23	229.4 ( 40.41 )	202.9 ( 42.00 )
Baseline CD4+ cell count,>200, n=293, 304	272.3 ( 11.73 )	269.4 ( 11.50 )
Age group-1, <35,n= 186, 187	266.0 ( 14.74 )	257.7 ( 14.68 )
Age group-1, 35 to <50, n=101, 110	273.6 ( 19.95 )	286.8 ( 19.22 )
Age group-1, >=50, n=31, 30	265.8 ( 36.14 )	233.1 ( 36.61 )
Female, n=44, 40	312.7 ( 30.12 )	307.6 ( 31.67 )
Male, n=274, 287	261.4 ( 12.07 )	259.3 ( 11.81 )
Race group, White, n=221, 234	272.1 ( 13.49 )	258.3 ( 13.14 )
Race group, African Am/African H., n=35, 30	246.3 ( 33.90 )	303.7 ( 36.61 )
Race group, Asian, n=31, 27	224.0 ( 36.31 )	264.0 ( 38.57 )
Race group, Other, n=31, 36	312.0 ( 36.01 )	278.9 ( 33.56 )

Notes
[116] - ITT-E Population.
[117] - ITT-E Population.

Statistical Analysis 1

Statistical analysis description

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-34.1

upper limit

Statistical Analysis 2

Statistical analysis description

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

14.7

Confidence interval

level

95%

sides

2-sided

lower limit

-55.6

upper limit

84.9

Statistical Analysis 3

Statistical analysis description

Baseline CD4+ cell count,<=200. Following covariates were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and Baseline CD4+ cell count interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

26.5

Confidence interval

level

95%

sides

2-sided

lower limit

-87.3

upper limit

140.3

Statistical Analysis 4

Statistical analysis description

Baseline CD4+ cell count,>200. Following covariates were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and Baseline CD4+ cell count interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-29.4

upper limit

35.1

Statistical Analysis 5

Statistical analysis description

Age Group,<35. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

8.3

Confidence interval

level

95%

sides

2-sided

lower limit

-32.5

upper limit

49.1

Statistical Analysis 6

Statistical analysis description

Age Group,35 to <50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-13.3

Confidence interval

level

95%

sides

2-sided

lower limit

-67.6

upper limit

41.1

Statistical Analysis 7

Statistical analysis description

Age Group,>=50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

32.7

Confidence interval

level

95%

sides

2-sided

lower limit

-68.5

upper limit

133.9

Statistical Analysis 8

Statistical analysis description

Female. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

5.1

Confidence interval

level

95%

sides

2-sided

lower limit

-80.7

upper limit

90.8

Statistical Analysis 9

Statistical analysis description

Male. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-31.1

upper limit

35.3

Statistical Analysis 10

Statistical analysis description

Race group-white. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

13.7

Confidence interval

level

95%

sides

2-sided

lower limit

-23.2

upper limit

50.6

Statistical Analysis 11

Statistical analysis description

Race group-African Am/African H. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-57.4

Confidence interval

level

95%

sides

2-sided

lower limit

-155.3

upper limit

40.4

Statistical Analysis 12

Statistical analysis description

Race group-Asian. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-40.1

Confidence interval

level

95%

sides

2-sided

lower limit

-144.2

upper limit

Statistical Analysis 13

Statistical analysis description

Race group-Other. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

33.1

Confidence interval

level

95%

sides

2-sided

lower limit

-63.3

upper limit

129.6

Secondary: Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups

Top of page

End point title

Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups

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. It was evaluated by flow cytometry. Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[118]	359 ^[119]
Units: Cells/mm^3
arithmetic mean (standard error)
Baseline plasma HIV-1 RNA,<=100000, n=241,234	286.8 ( 14.36 )	277.8 ( 14.58 )
Baseline plasma HIV-1 RNA,>100000, n=55,58	338.2 ( 30.34 )	354.7 ( 29.35 )
Baseline CD4+ cell count,<=200, n=25, 19	264.8 ( 44.91 )	208.9 ( 51.25 )
Baseline CD4+ cell count,>200, n=271, 273	300.3 ( 13.54 )	297.9 ( 13.48 )
Age group, <35,n=171, 159	302.9 ( 17.05 )	277.1 ( 17.65 )
Age group-1, 35 to <50, n=95, 103	292.8 ( 22.82 )	329.2 ( 22.02 )
Age group-1, >=50, n=30, 30	274.1 ( 40.71 )	250.0 ( 40.60 )
Female, n=40, 37	355.0 ( 34.93 )	381.8 ( 36.37 )
Male, n=256, 255	287.7 ( 13.81 )	279.6 ( 13.85 )
Race group, White, n=202, 211	300.0 ( 15.61 )	296.5 ( 15.29 )
Race group, African Am/African H., n=34, 24	256.4 ( 38.04 )	377.6 ( 45.25 )
Race group, Asian, n=29, 25	258.5 ( 41.57 )	245.4 ( 44.36 )
Race group, Other, n=31, 32	355.0 ( 39.84 )	240.7 ( 39.35 )

Notes
[118] - ITT-E Population.
[119] - ITT-E Population.

Statistical Analysis 4

Statistical analysis description

Baseline CD4+ cell count,>200. Following covariates were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and Baseline CD4+ cell count interaction.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-35.2

upper limit

39.9

Statistical Analysis 3

Statistical analysis description

Baseline CD4+ cell count,<=200. Following covariates were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and Baseline CD4+ cell count interaction.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-77.2

upper limit

189.1

Statistical Analysis 2

Statistical analysis description

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-16.6

Confidence interval

level

95%

sides

2-sided

lower limit

-98.9

upper limit

65.8

Statistical Analysis 1

Statistical analysis description

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

9.1

Confidence interval

level

95%

sides

2-sided

lower limit

-31.1

upper limit

49.2

Statistical Analysis 9

Statistical analysis description

Male. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

8.1

Confidence interval

level

95%

sides

2-sided

lower limit

-30.3

upper limit

46.5

Statistical Analysis 10

Statistical analysis description

Race group-white. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-39.4

upper limit

46.3

Statistical Analysis 11

Statistical analysis description

Race group-African Am/African H. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-121.2

Confidence interval

level

95%

sides

2-sided

lower limit

-237.2

upper limit

-5.1

Statistical Analysis 12

Statistical analysis description

Race group-Asian. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

13.1

Confidence interval

level

95%

sides

2-sided

lower limit

-106.4

upper limit

132.6

Statistical Analysis 8

Statistical analysis description

Female. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-26.9

Confidence interval

level

95%

sides

2-sided

lower limit

-125.9

upper limit

72.2

Statistical Analysis 13

Statistical analysis description

Race group-Other. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race, and treatment and race interaction.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

114.3

Confidence interval

level

95%

sides

2-sided

lower limit

4.6

upper limit

224

Statistical Analysis 6

Statistical analysis description

Age Group,35 to <50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-36.4

Confidence interval

level

95%

sides

2-sided

lower limit

-98.6

upper limit

25.8

Statistical Analysis 5

Statistical analysis description

Age Group,<35. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

25.8

Confidence interval

level

95%

sides

2-sided

lower limit

-22.3

upper limit

Statistical Analysis 7

Statistical analysis description

Age Group,>=50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

24.1

Confidence interval

level

95%

sides

2-sided

lower limit

-89

upper limit

137.2

Secondary: Change from Baseline in European Quality of life [EuroQoL] – 5 Dimensions – 5 Levels (EQ-5D-5L) utility score at Weeks 4, 24, 48

Top of page

End point title

Change from Baseline in European Quality of life [EuroQoL] – 5 Dimensions – 5 Levels (EQ-5D-5L) utility score at Weeks 4, 24, 48

End point description

EQ-5D-5L questionnaire provides profile of participant function and global health state rating. Five-item measure has 1 question assessing each of 5 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,5=extreme problems. The health state is defined by combining the levels of answers from each of the 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. MMRM was run on LOCF dataset. Baseline was the latest pre-dose assessment and change from Baseline=post-dose value minus Baseline value. Only those participants available at specified time points were analyzed(represented by n=X in category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Weeks 4, 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[120]	359 ^[121]
Units: Scores on a scale
least squares mean (standard error)
Week 4, n=359, 355	0.0111 ( 0.00326 )	0.0130 ( 0.00510 )
Week 24, n=360, 358	0.0207 ( 0.00310 )	0.0203 ( 0.00347 )
Week 48, n=360, 358	0.0189 ( 0.00362 )	0.0208 ( 0.00342 )

Notes
[120] - ITT-E Population.
[121] - ITT-E Population.

Statistical Analysis 1

Statistical analysis description

Week 4. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA , Baseline CD4+ cell count , and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.759

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.0019

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0137

upper limit

0.01

Statistical Analysis 3

Statistical analysis description

Week 48. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA , Baseline CD4+ cell count , and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.703

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.0019

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0117

upper limit

0.0079

Statistical Analysis 2

Statistical analysis description

Week 24. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA , Baseline CD4+ cell count , and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.943

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.0003

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0088

upper limit

0.0095

Secondary: Change From Baseline in EQ-5D-5L Utility Score at Week 96

Top of page

End point title

Change From Baseline in EQ-5D-5L Utility Score at Week 96

End point description

EQ-5D-5L questionnaire provides profile of participant function and global health state rating. Five-item measure has 1 question assessing each of 5 dimensions: 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. MMRM was run on LOCF dataset. Baseline was the latest pre-dose assessment and change from Baseline=post-dose value minus Baseline value. Adjusted mean and standard error is presented. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[122]	358 ^[123]
Units: Scores on a scale
arithmetic mean (standard error)	0.0168 ( 0.00339 )	0.0171 ( 0.00424 )

Notes
[122] - ITT-E Population.
[123] - ITT-E Population.

Subject Analysis

Statistical analysis description

Week 96. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

718

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.957

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.0003

Confidence interval

level

95%

sides

2-sided

lower limit

-0.011

upper limit

0.0104

Secondary: Change From Baseline in EQ-5D-5L Utility Score at Week 144

Top of page

End point title

Change From Baseline in EQ-5D-5L Utility Score at Week 144

End point description

EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. Five-item measure has 1 question assessing each of 5 dimensions: 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 5digit 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. MMRM was run on LOCF dataset. Baseline was latest pre-dose assessment and change from Baseline=post-dose value minus Baseline value.Adjusted mean and standard error is presented. Only those participants available at specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	360 ^[124]	358 ^[125]
Units: Scores on a scale
arithmetic mean (standard error)	0.0210 ( 0.00346 )	0.0131 ( 0.00441 )

Notes
[124] - ITT-E Population.
[125] - ITT-E Population.

Subject Analysis

Statistical analysis description

Week 144. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

718

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.162

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.0079

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0032

upper limit

0.0189

Secondary: Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24, 48

Top of page

End point title

Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24, 48

End point description

EQ-5D-5L questionnaire provided 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, using the observed margins (OM) option. Baseline was the latest pre-dose assessment value and change from Baseline=post-dose value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Weeks 4, 24, 48

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	360 ^[126]	359 ^[127]
Units: Scores on a scale
least squares mean (standard error)
Week 4, n=358, 355	1.8 ( 0.50 )	3.1 ( 0.41 )
Week 24, n=359, 358	3.9 ( 0.43 )	4.5 ( 0.48 )
Week 48, n=359, 358	4.0 ( 0.43 )	4.6 ( 0.48 )

Notes
[126] - ITT-E Population.
[127] - ITT-E Population.

Subject Analysis 1

Statistical analysis description

Week 4. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.045

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

Subject Analysis 3

Statistical analysis description

Week 48. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.328

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.6

Subject Analysis 2

Statistical analysis description

Week 24. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

719

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.358

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.7

Secondary: Change From Baseline in EQ-5D-5L Thermometer Scores at Week 96

Top of page

End point title

Change From Baseline in EQ-5D-5L Thermometer Scores at Week 96

End point description

EQ-5D-5L questionnaire provided 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, using the observed margins (OM) option. Baseline was the latest pre-dose assessment value and change from Baseline=post-dose value minus Baseline value. Adjusted mean and standard error is presented. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 96

End point values	DTG + 3TC	DTG + TDF/FTC
Number of subjects analysed	359 ^[128]	358 ^[129]
Units: Scores on a scale
arithmetic mean (standard error)	4.4 ( 0.45 )	5.1 ( 0.52 )

Notes
[128] - ITT-E Population.
[129] - ITT-E Population.

Subject Analysis

Statistical analysis description

Week 96. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC v DTG + TDF/FTC

Number of subjects included in analysis

717

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.318

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

0.7

Secondary: Change From Baseline in EQ-5D-5L Thermometer Scores at Week 144

Top of page

End point title

Change From Baseline in EQ-5D-5L Thermometer Scores at Week 144

End point description

EQ-5D-5L questionnaire provided 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, using the observed margins (OM) option. Baseline was the latest pre-dose assessment value and change from Baseline=post-dose value minus Baseline value. Adjusted mean and standard error is presented. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 144

End point values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects analysed	359 ^[130]	358 ^[131]
Units: Scores on a scale
arithmetic mean (standard error)	4.8 ( 0.44 )	4.5 ( 0.51 )

Notes
[130] - ITT-E Population.
[131] - ITT-E Population.

Subject Analysis

Statistical analysis description

Week 144. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit as factors and covariate, with visit as the repeated factor.

Comparison groups

DTG + 3TC - Double-blind Phase + Open-label Phase v DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Number of subjects included in analysis

717

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.674

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

1.6

Adverse events

Top of page

Timeframe for reporting adverse events

All-cause mortality, SAEs and non-SAEs were collected up to Week 148 in Double-blind Phase + Open-label Phase and from Week 148 to Week 280 in Continuation Phase

Adverse event reporting additional description

All-cause mortality, SAEs and non-SAEs were reported for the Safety Population for the Double-blind Phase and Double-blind Phase + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase (which comprised of all participants who received at least 1 dose of study treatment after entering the Continuation Phase).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.0

Reporting group title

DTG + 3TC - Double-blind Phase + Open-label Phase

Reporting group description

Reporting group title

DTG + TDF/FTC - Double-blind Phase + Open-label Phase

Reporting group description

Reporting group title

DTG + 3TC - Continuation Phase

Reporting group description

Participants received a DTG + 3TC administered orally, once daily from Week 148 to Week 280 in a continuation phase.

Serious adverse events	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase	DTG + 3TC - Continuation Phase
Total subjects affected by serious adverse events
subjects affected / exposed	39 / 360 (10.83%)	47 / 359 (13.09%)	9 / 252 (3.57%)
number of deaths (all causes)	2	1	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts
subjects affected / exposed	2 / 360 (0.56%)	3 / 359 (0.84%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
B-cell lymphoma
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Burkitt's lymphoma
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anal cancer stage 0
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Non-Hodgkin's lymphoma
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Death
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Immune system disorders
Jarisch-Herxheimer reaction
subjects affected / exposed	0 / 360 (0.00%)	0 / 359 (0.00%)	1 / 252 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 360 (0.00%)	0 / 359 (0.00%)	1 / 252 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	1 / 360 (0.28%)	4 / 359 (1.11%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	1 / 1	2 / 6	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	5 / 360 (1.39%)	2 / 359 (0.56%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 5	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Alcoholic psychosis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Substance-induced psychotic disorder
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	1 / 252 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Major depression
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fracture of penis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Fracture
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intentional overdose
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Post procedural complication
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Penetrating abdominal trauma
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Multiple fractures
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thermal burn
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Joint dislocation
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Traumatic arthritis
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	0 / 360 (0.00%)	0 / 359 (0.00%)	1 / 252 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pericarditis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Sciatica
subjects affected / exposed	1 / 360 (0.28%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Generalised tonic-clonic seizure
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 360 (0.00%)	2 / 359 (0.56%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 360 (0.00%)	0 / 359 (0.00%)	1 / 252 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypoaesthesia
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Migraine with aura
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Ophthalmic vein thrombosis
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 360 (0.28%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal hernia
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haematemesis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	0 / 360 (0.00%)	3 / 359 (0.84%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatotoxicity
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gallbladder rupture
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Urethral meatus stenosis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	1 / 360 (0.28%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Calculus urinary
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Acute hepatitis C
subjects affected / exposed	2 / 360 (0.56%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 360 (0.28%)	2 / 359 (0.56%)	1 / 252 (0.40%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatitis A
subjects affected / exposed	3 / 360 (0.83%)	3 / 359 (0.84%)	1 / 252 (0.40%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacterial colitis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Epididymitis
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Salmonellosis
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Soft tissue infection
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tuberculous pleurisy
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatitis C
subjects affected / exposed	0 / 360 (0.00%)	0 / 359 (0.00%)	1 / 252 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Varicella zoster virus infection
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 360 (0.00%)	0 / 359 (0.00%)	3 / 252 (1.19%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic tonsillitis
subjects affected / exposed	0 / 360 (0.00%)	0 / 359 (0.00%)	1 / 252 (0.40%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 360 (0.28%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis orbital
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Enteritis infectious
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis cryptosporidial
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Labyrinthitis
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Perirectal abscess
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 360 (0.00%)	2 / 359 (0.56%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syphilis
subjects affected / exposed	1 / 360 (0.28%)	0 / 359 (0.00%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Shigella infection
subjects affected / exposed	0 / 360 (0.00%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase	DTG + 3TC - Continuation Phase
Total subjects affected by non serious adverse events
subjects affected / exposed	273 / 360 (75.83%)	276 / 359 (76.88%)	45 / 252 (17.86%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts
subjects affected / exposed	10 / 360 (2.78%)	15 / 359 (4.18%)	0 / 252 (0.00%)
occurrences all number	13	17	0
Vascular disorders
Hypertension
subjects affected / exposed	14 / 360 (3.89%)	5 / 359 (1.39%)	0 / 252 (0.00%)
occurrences all number	16	5	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	10 / 360 (2.78%)	9 / 359 (2.51%)	0 / 252 (0.00%)
occurrences all number	13	9	0
Influenza like illness
subjects affected / exposed	16 / 360 (4.44%)	11 / 359 (3.06%)	0 / 252 (0.00%)
occurrences all number	20	14	0
Pyrexia
subjects affected / exposed	11 / 360 (3.06%)	9 / 359 (2.51%)	0 / 252 (0.00%)
occurrences all number	11	12	0
Asthenia
subjects affected / exposed	10 / 360 (2.78%)	14 / 359 (3.90%)	0 / 252 (0.00%)
occurrences all number	12	14	0
Reproductive system and breast disorders
Erectile dysfunction
subjects affected / exposed	9 / 360 (2.50%)	4 / 359 (1.11%)	0 / 252 (0.00%)
occurrences all number	9	4	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	17 / 360 (4.72%)	16 / 359 (4.46%)	0 / 252 (0.00%)
occurrences all number	21	17	0
Cough
subjects affected / exposed	11 / 360 (3.06%)	15 / 359 (4.18%)	0 / 252 (0.00%)
occurrences all number	12	15	0
Rhinorrhoea
subjects affected / exposed	3 / 360 (0.83%)	10 / 359 (2.79%)	0 / 252 (0.00%)
occurrences all number	5	11	0
Psychiatric disorders
Insomnia
subjects affected / exposed	17 / 360 (4.72%)	23 / 359 (6.41%)	0 / 252 (0.00%)
occurrences all number	17	28	0
Anxiety
subjects affected / exposed	17 / 360 (4.72%)	18 / 359 (5.01%)	0 / 252 (0.00%)
occurrences all number	17	19	0
Depression
subjects affected / exposed	12 / 360 (3.33%)	13 / 359 (3.62%)	0 / 252 (0.00%)
occurrences all number	14	16	0
Investigations
Weight increased
subjects affected / exposed	10 / 360 (2.78%)	9 / 359 (2.51%)	0 / 252 (0.00%)
occurrences all number	10	10	0
Injury, poisoning and procedural complications
Ligament sprain
subjects affected / exposed	8 / 360 (2.22%)	6 / 359 (1.67%)	0 / 252 (0.00%)
occurrences all number	8	6	0
Nervous system disorders
Headache
subjects affected / exposed	33 / 360 (9.17%)	44 / 359 (12.26%)	0 / 252 (0.00%)
occurrences all number	49	60	0
Dizziness
subjects affected / exposed	9 / 360 (2.50%)	18 / 359 (5.01%)	0 / 252 (0.00%)
occurrences all number	11	20	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	49 / 360 (13.61%)	53 / 359 (14.76%)	0 / 252 (0.00%)
occurrences all number	55	61	0
Nausea
subjects affected / exposed	16 / 360 (4.44%)	31 / 359 (8.64%)	0 / 252 (0.00%)
occurrences all number	17	33	0
Haemorrhoids
subjects affected / exposed	16 / 360 (4.44%)	12 / 359 (3.34%)	0 / 252 (0.00%)
occurrences all number	17	12	0
Constipation
subjects affected / exposed	9 / 360 (2.50%)	14 / 359 (3.90%)	0 / 252 (0.00%)
occurrences all number	9	14	0
Toothache
subjects affected / exposed	7 / 360 (1.94%)	14 / 359 (3.90%)	0 / 252 (0.00%)
occurrences all number	8	15	0
Abdominal pain
subjects affected / exposed	9 / 360 (2.50%)	17 / 359 (4.74%)	0 / 252 (0.00%)
occurrences all number	10	17	0
Vomiting
subjects affected / exposed	11 / 360 (3.06%)	11 / 359 (3.06%)	0 / 252 (0.00%)
occurrences all number	11	12	0
Abdominal pain upper
subjects affected / exposed	5 / 360 (1.39%)	9 / 359 (2.51%)	0 / 252 (0.00%)
occurrences all number	6	13	0
Gastrooesophageal reflux disease
subjects affected / exposed	8 / 360 (2.22%)	9 / 359 (2.51%)	0 / 252 (0.00%)
occurrences all number	9	10	0
Gastritis
subjects affected / exposed	9 / 360 (2.50%)	7 / 359 (1.95%)	0 / 252 (0.00%)
occurrences all number	10	7	0
Odynophagia
subjects affected / exposed	2 / 360 (0.56%)	9 / 359 (2.51%)	0 / 252 (0.00%)
occurrences all number	5	10	0
Anogenital dysplasia
subjects affected / exposed	8 / 360 (2.22%)	4 / 359 (1.11%)	0 / 252 (0.00%)
occurrences all number	10	4	0
Proctitis
subjects affected / exposed	6 / 360 (1.67%)	8 / 359 (2.23%)	0 / 252 (0.00%)
occurrences all number	8	9	0
Dental caries
subjects affected / exposed	8 / 360 (2.22%)	2 / 359 (0.56%)	0 / 252 (0.00%)
occurrences all number	8	2	0
Irritable bowel syndrome
subjects affected / exposed	8 / 360 (2.22%)	1 / 359 (0.28%)	0 / 252 (0.00%)
occurrences all number	10	1	0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	10 / 360 (2.78%)	13 / 359 (3.62%)	0 / 252 (0.00%)
occurrences all number	13	16	0
Urticaria
subjects affected / exposed	8 / 360 (2.22%)	13 / 359 (3.62%)	0 / 252 (0.00%)
occurrences all number	12	15	0
Pruritus
subjects affected / exposed	6 / 360 (1.67%)	11 / 359 (3.06%)	0 / 252 (0.00%)
occurrences all number	9	12	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	10 / 360 (2.78%)	3 / 359 (0.84%)	0 / 252 (0.00%)
occurrences all number	10	3	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	27 / 360 (7.50%)	23 / 359 (6.41%)	0 / 252 (0.00%)
occurrences all number	32	30	0
Arthralgia
subjects affected / exposed	17 / 360 (4.72%)	25 / 359 (6.96%)	0 / 252 (0.00%)
occurrences all number	21	26	0
Neck pain
subjects affected / exposed	10 / 360 (2.78%)	6 / 359 (1.67%)	0 / 252 (0.00%)
occurrences all number	10	11	0
Myalgia
subjects affected / exposed	8 / 360 (2.22%)	7 / 359 (1.95%)	0 / 252 (0.00%)
occurrences all number	9	12	0
Infections and infestations
Pharyngitis
subjects affected / exposed	24 / 360 (6.67%)	33 / 359 (9.19%)	0 / 252 (0.00%)
occurrences all number	31	35	0
Upper respiratory tract infection
subjects affected / exposed	47 / 360 (13.06%)	28 / 359 (7.80%)	7 / 252 (2.78%)
occurrences all number	75	44	7
Nasopharyngitis
subjects affected / exposed	44 / 360 (12.22%)	69 / 359 (19.22%)	0 / 252 (0.00%)
occurrences all number	59	103	0
Bronchitis
subjects affected / exposed	12 / 360 (3.33%)	21 / 359 (5.85%)	0 / 252 (0.00%)
occurrences all number	14	24	0
Gastroenteritis
subjects affected / exposed	21 / 360 (5.83%)	20 / 359 (5.57%)	6 / 252 (2.38%)
occurrences all number	21	25	6
Tonsillitis
subjects affected / exposed	13 / 360 (3.61%)	9 / 359 (2.51%)	0 / 252 (0.00%)
occurrences all number	14	13	0
Gonorrhoea
subjects affected / exposed	12 / 360 (3.33%)	12 / 359 (3.34%)	0 / 252 (0.00%)
occurrences all number	14	15	0
Respiratory tract infection viral
subjects affected / exposed	14 / 360 (3.89%)	12 / 359 (3.34%)	8 / 252 (3.17%)
occurrences all number	20	19	10
Syphilis
subjects affected / exposed	26 / 360 (7.22%)	30 / 359 (8.36%)	10 / 252 (3.97%)
occurrences all number	30	34	11
Influenza
subjects affected / exposed	16 / 360 (4.44%)	25 / 359 (6.96%)	0 / 252 (0.00%)
occurrences all number	17	27	0
Chlamydial infection
subjects affected / exposed	10 / 360 (2.78%)	13 / 359 (3.62%)	0 / 252 (0.00%)
occurrences all number	13	13	0
Rhinitis
subjects affected / exposed	5 / 360 (1.39%)	16 / 359 (4.46%)	0 / 252 (0.00%)
occurrences all number	6	18	0
Genital herpes
subjects affected / exposed	4 / 360 (1.11%)	10 / 359 (2.79%)	0 / 252 (0.00%)
occurrences all number	4	14	0
COVID-19
subjects affected / exposed	0 / 360 (0.00%)	0 / 359 (0.00%)	15 / 252 (5.95%)
occurrences all number	0	0	15
Suspected COVID-19
subjects affected / exposed	0 / 360 (0.00%)	0 / 359 (0.00%)	7 / 252 (2.78%)
occurrences all number	0	0	8
Anal chlamydia infection
subjects affected / exposed	10 / 360 (2.78%)	16 / 359 (4.46%)	0 / 252 (0.00%)
occurrences all number	12	21	0
Sinusitis
subjects affected / exposed	12 / 360 (3.33%)	12 / 359 (3.34%)	0 / 252 (0.00%)
occurrences all number	14	13	0
Urinary tract infection
subjects affected / exposed	11 / 360 (3.06%)	9 / 359 (2.51%)	0 / 252 (0.00%)
occurrences all number	14	12	0
Proctitis gonococcal
subjects affected / exposed	9 / 360 (2.50%)	9 / 359 (2.51%)	0 / 252 (0.00%)
occurrences all number	12	11	0
Respiratory tract infection
subjects affected / exposed	10 / 360 (2.78%)	8 / 359 (2.23%)	0 / 252 (0.00%)
occurrences all number	12	10	0
Secondary syphilis
subjects affected / exposed	7 / 360 (1.94%)	10 / 359 (2.79%)	0 / 252 (0.00%)
occurrences all number	7	11	0
Folliculitis
subjects affected / exposed	8 / 360 (2.22%)	8 / 359 (2.23%)	0 / 252 (0.00%)
occurrences all number	16	9	0
Gingivitis
subjects affected / exposed	9 / 360 (2.50%)	4 / 359 (1.11%)	0 / 252 (0.00%)
occurrences all number	13	4	0
Oral herpes
subjects affected / exposed	9 / 360 (2.50%)	6 / 359 (1.67%)	0 / 252 (0.00%)
occurrences all number	13	7	0
Conjunctivitis
subjects affected / exposed	6 / 360 (1.67%)	9 / 359 (2.51%)	0 / 252 (0.00%)
occurrences all number	6	10	0
Herpes zoster
subjects affected / exposed	8 / 360 (2.22%)	5 / 359 (1.39%)	0 / 252 (0.00%)
occurrences all number	8	5	0
Urethritis
subjects affected / exposed	8 / 360 (2.22%)	5 / 359 (1.39%)	0 / 252 (0.00%)
occurrences all number	9	5	0
Urethritis gonococcal
subjects affected / exposed	3 / 360 (0.83%)	8 / 359 (2.23%)	0 / 252 (0.00%)
occurrences all number	4	9	0
Cellulitis
subjects affected / exposed	8 / 360 (2.22%)	2 / 359 (0.56%)	0 / 252 (0.00%)
occurrences all number	10	3	0
Viral infection
subjects affected / exposed	4 / 360 (1.11%)	8 / 359 (2.23%)	0 / 252 (0.00%)
occurrences all number	4	8	0
Metabolism and nutrition disorders
Vitamin D deficiency
subjects affected / exposed	28 / 360 (7.78%)	20 / 359 (5.57%)	0 / 252 (0.00%)
occurrences all number	29	20	0
Hypertriglyceridaemia
subjects affected / exposed	9 / 360 (2.50%)	6 / 359 (1.67%)	0 / 252 (0.00%)
occurrences all number	10	6	0
Decreased appetite
subjects affected / exposed	8 / 360 (2.22%)	3 / 359 (0.84%)	0 / 252 (0.00%)
occurrences all number	8	3	0
Dyslipidaemia
subjects affected / exposed	8 / 360 (2.22%)	3 / 359 (0.84%)	0 / 252 (0.00%)
occurrences all number	8	3	0

More information

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Were there any global substantial amendments to the protocol? Yes

29 Nov 2017

Amendment 1: Double barrier method of contraception (male condom combined with a vaginal spermicide) was added as a permitted method for preventing pregnancy in females of reproductive potential. Exclusion criterion 15 (limitations on investigational drug use) was broadened to include additional countries as needed. Inclusion of Portugal was required by Portuguese National Ethics Committee for Clinical Research. Assessment of weight at Weeks 96 and 144 was added to monitor incidence of significant weight gain with DTG use. Assessment of inflammation biomarkers ([interleukin {IL}-6, high sensitivity C-reactive protein {hs-CRP}) at Day1, and Weeks48, 96, 144 and Assessment of telomere length at Day 1, and Weeks 96 and 144, were added as new exploratory endpoints. For clarification purposes, peripheral blood mononuclear cell (PBMC) sample in Time and Events table and Human immuno deficiency virus [HIV-1] Exploratory Analyses was renamed as a whole blood sample. The Day 1 PBMC sample (now named whole blood sample) originally designated for virology use was additionally designated for telomere length measurement, where possible. Additional whole blood samples were added for measurement of telomere length at Week 96 and Week 144. A description of commercial image DTG tablets was added to Section 6.1 (Investigational Product and Other Study Treatment) to allow use of commercial material as well as clinical trial material. The physical description for open-label lamivudine in Section 6.1 was corrected. Standard procedures for forwarding pregnancy information to the Antiretroviral Pregnancy Register were added. For clarification purposes, the AE severity grading’s in Appendix 7, Section 12.7.6 (Evaluating adverse events [AEs] and serious adverse events [SAEs]) were updated to be consistent with Appendix 6, Section 12.6. (Division of AIDS table for Grading Severity of Adult and Pediatric AEs). This change has no impact on the investigators evaluation of AEs.

14 Jun 2018

Amendment 2: 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 dolutegravir at the time of conception. Changes were also made to update the references to the DTG Investigator’s Brochure to reflect the most current versions. • The Risk Assessment table (Section 4.6.1) was updated to include language regarding risk and mitigation of neural tube defects. • The withdrawal criteria (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, should also be withdrawn from the study. • The Time and Events table (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 (Section 12.9.1) was updated to exclude the double barrier method of contraception, which does not meet updated GlaxoSmithKline/ViiV criteria for a highly effective method.

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, randomised, double-blind, multicentre, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of dolutegravir plus lamivudine compared to dolutegravir plus tenofovir/emtricitabine in HIV-1-infected treatment-naïve adults

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants with plasma Human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL (c/mL) at Week 48

Primary: Percentage of participants with plasma Human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL (c/mL) at Week 48

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

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

Secondary: Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 96

Secondary: Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 96

Secondary: Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 144

Secondary: Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 144

Secondary: Time to Viral Suppression (HIV-1 RNA <50 c/mL) up to Week 144

Secondary: Time to Viral Suppression (HIV-1 RNA <50 c/mL) up to Week 144

Secondary: CD4+ cell counts at Weeks 24 and 48

Secondary: CD4+ cell counts at Weeks 24 and 48

Secondary: CD4+ Cell Counts at Week 96

Secondary: CD4+ Cell Counts at Week 96

Secondary: CD4+ Cell Counts at Week 144

Secondary: CD4+ Cell Counts at Week 144

Secondary: Changes from Baseline in CD4+ cell counts at Week 24 and 48

Secondary: Changes from Baseline in CD4+ cell counts at Week 24 and 48

Secondary: Changes From Baseline in CD4+ Cell Counts at Week 96

Secondary: Changes From Baseline in CD4+ Cell Counts at Week 96

Secondary: Changes From Baseline in CD4+ Cell Counts at Week 144

Secondary: Changes From Baseline in CD4+ Cell Counts at Week 144

Secondary: Number of Participants With HIV-1 Disease Progression up to Week 144

Secondary: Number of Participants With HIV-1 Disease Progression up to Week 144

Secondary: Number of Participants With Treatment-emergent Genotypic Resistance up to Week 144

Secondary: Number of Participants With Treatment-emergent Genotypic Resistance up to Week 144

Secondary: Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144

Secondary: Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144

Secondary: Number of Participants With Any AE and SAE up to Week 148

Secondary: Number of Participants With Any AE and SAE up to Week 148

Secondary: Number of Participants With AEs by Maximum Severity Grades up to Week 148

Secondary: Number of Participants With AEs by Maximum Severity Grades up to Week 148

Secondary: Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade up to Week 148

Secondary: Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade up to Week 148

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 Chemistry Toxicities up to Week 144

Secondary: Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144

Secondary: Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48, 96

Secondary: Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48, 96

Secondary: Number of Participants Who Discontinue Treatment Due to AEs Over Week 144

Secondary: Number of Participants Who Discontinue Treatment Due to AEs Over Week 144

Secondary: Change from Baseline in renal biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48

Secondary: Change from Baseline in renal biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48

Secondary: Change From Baseline in Renal Biomarker-Serum Cystatin C at Week 96

Secondary: Change From Baseline in Renal Biomarker-Serum Cystatin C at Week 96

Secondary: Change From Baseline in Renal Biomarker-Serum Cystatin C at Week 144

Secondary: Change From Baseline in Renal Biomarker-Serum Cystatin C at Week 144

Secondary: Change From Baseline in Renal Biomarker-Serum RBP at Week 96

Secondary: Change From Baseline in Renal Biomarker-Serum RBP at Week 96

Secondary: Change From Baseline in Renal Biomarker-Serum RBP at Week 144

Secondary: Change From Baseline in Renal Biomarker-Serum RBP at Week 144

Secondary: Change from Baseline in renal biomarkers-Serum GFR from cystatin C Adjusted using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR from creatinine adjusted using CKD-EPI at Weeks 24, 48

Secondary: Change from Baseline in renal biomarkers-Serum GFR from cystatin C Adjusted using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR from creatinine adjusted using CKD-EPI at Weeks 24, 48

Secondary: Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI method at Week 96

Secondary: Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI method at Week 96

Secondary: Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI method at Week 144

Secondary: Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI method at Week 144

Secondary: Change from Baseline in renal biomarker-Serum or Plasma Creatinine at Weeks 24, 48

Secondary: Change from Baseline in renal biomarker-Serum or Plasma Creatinine at Weeks 24, 48

Secondary: Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Week 96

Secondary: Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Week 96

Secondary: Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Week 144

Secondary: Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Week 144

Secondary: Ratio to Baseline in renal biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48

Secondary: Ratio to Baseline in renal biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48

Secondary: Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 96

Secondary: Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 96

Secondary: Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 144

Secondary: Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 144

Clinical Trial Results:
A Phase III, randomised, double-blind, multicentre, parallel-group, non-inferiority study evaluating the efficacy, safety, and tolerability of dolutegravir plus lamivudine compared to dolutegravir plus tenofovir/emtricitabine in HIV-1-infected treatment-naïve adults