Download PDF

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	2015-004418-95
Trial protocol	DE ES BE NL PT FR IT
Global end of trial date	15 Aug 2022

Results information
Results version number	v2(current)
This version publication date	17 Aug 2023
First version publication date	11 Apr 2019
Other versions	v1
Version creation reason

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

204861

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 Sep 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

15 Aug 2022

Was the trial ended prematurely?

Main objective of the trial

To demonstrate non-inferior antiviral activity of dolutegravir plus lamivudine ( DTG + 3TC) versus dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) at 48 weeks in HIV-1-infected, ART-naïve participants

Protection of trial subjects

Not applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

21 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

Russian Federation: 75

Country: Number of subjects enrolled

South Africa: 7

Country: Number of subjects enrolled

Spain: 68

Country: Number of subjects enrolled

Taiwan: 62

Country: Number of subjects enrolled

United States: 113

Country: Number of subjects enrolled

United Kingdom: 9

Country: Number of subjects enrolled

Argentina: 105

Country: Number of subjects enrolled

Australia: 6

Country: Number of subjects enrolled

Belgium: 22

Country: Number of subjects enrolled

Canada: 33

Country: Number of subjects enrolled

France: 27

Country: Number of subjects enrolled

Germany: 19

Country: Number of subjects enrolled

Italy: 78

Country: Number of subjects enrolled

Korea, Republic of: 7

Country: Number of subjects enrolled

Mexico: 60

Country: Number of subjects enrolled

Netherlands: 4

Country: Number of subjects enrolled

Portugal: 16

Country: Number of subjects enrolled

Romania: 8

Worldwide total number of subjects

719

EEA total number of subjects

242

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)

715

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

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

Screening details

Total of 719 participants were enrolled and randomized. Five participants were randomized but not treated. A total of 714 participants received at least one dose of study treatment, following randomization 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

Investigator, Subject

Are arms mutually exclusive

Yes

DTG + 3TC-Double blind phase

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

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

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-Double blind phase

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

Dolutegravir

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.

Investigational medicinal product name

Tenofovir disoproxil fumarate/emtricitabine fixed-dose combination

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.

Number of subjects in period 1 ^[1]	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Started	356	358
Completed	257	293
Not completed	99	65
Physician decision	12	8
Consent withdrawn by subject	24	11
Randomized, but did not receive treatment	3	2
Adverse event, non-fatal	14	13
Protocol Deviation	7	7
Protocol Withdrawal Criterion Met	4	7
Lost to follow-up	30	13
Lack of efficacy	5	4

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: Total of 719 participants were enrolled and randomized. Five participants were randomized but not treated. A total of 714 participants received at least one dose of study treatment, following randomization creating the intent to treat exposed (ITT-E) population

Baseline characteristics

Top of page

Reporting group title

Overall study

Reporting group description

Reporting group values	Overall study	Total
Number of subjects	714
Age categorical
Baseline Characteristic data are reported for the Intent-to-Treat Exposed (ITT-E) Population which consisted of all randomized participants who received at least one dose of study treatment.
Units: Participants
Age Continuous
Baseline Characteristic data are reported for the Intent-to-Treat Exposed (ITT-E) Population which consisted of all randomized participants who received at least one dose of study treatment.
Units: years
arithmetic mean (standard deviation)	34.5 ( 10.31 )	-
Sex: Female, Male
Baseline Characteristic data are reported for the Intent-to-Treat Exposed (ITT-E) Population which consisted of all randomized participants who received at least one dose of study treatment.
Units: Participants
Female	111	111
Male	603	603
Race/Ethnicity, Customized
Baseline Characteristic data are reported for the Intent-to-Treat Exposed (ITT-E) Population which consisted of all randomized participants who received at least one dose of study treatment.
Units: Subjects
American (Am) Indian or Alaska (Al.) native	59	59
Asian-Central/South Asian heritage (H.)	4	4
Asian - East Asian H.	69	69
Asian - South East Asian H.	6	6
Black or African Am	75	75
Native Hawaiian or other Pacific Islander	2	2
White (Wt)-Arabic/North African H.	10	10
Wt-Wt/Caucasian (Ca.)/European (Eu.) H.	481	481
Multiple	8	8

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

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in double blind phase

Subject analysis set title

DTG + 3TC Double blind Phase

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase

Subject analysis set title

DTG + 3TC - Double-blind Phase

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind 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 + 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 sets values	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase	DTG + 3TC Double blind Phase	DTG + 3TC Double blind Phase	DTG + 3TC - Double-blind Phase	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase	DTG + 3TC - Double-blind Phase + Open-label Phase	DTG + TDF/FTC - Double-blind Phase + Open-label Phase
Number of subjects	356	358	356	301	301	8	8	5	6
Age categorical
Baseline Characteristic data are reported for the Intent-to-Treat Exposed (ITT-E) Population which consisted of all randomized participants who received at least one dose of study treatment.
Units: Participants
Age Continuous
Baseline Characteristic data are reported for the Intent-to-Treat Exposed (ITT-E) Population which consisted of all randomized participants who received at least one dose of study treatment.
Units: years
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )	( )	( )	( )
Sex: Female, Male
Baseline Characteristic data are reported for the Intent-to-Treat Exposed (ITT-E) Population which consisted of all randomized participants who received at least one dose of study treatment.
Units: Participants
Female	59	52
Male	297	306
Race/Ethnicity, Customized
Baseline Characteristic data are reported for the Intent-to-Treat Exposed (ITT-E) Population which consisted of all randomized participants who received at least one dose of study treatment.
Units: Subjects
American (Am) Indian or Alaska (Al.) native	31	28
Asian-Central/South Asian heritage (H.)	0	4
Asian - East Asian H.	33	36
Asian - South East Asian H.	4	2
Black or African Am	39	36
Native Hawaiian or other Pacific Islander	2	0
White (Wt)-Arabic/North African H.	5	5
Wt-Wt/Caucasian (Ca.)/European (Eu.) H.	239	242
Multiple	3	5

End points

Top of page

Reporting group title

DTG + 3TC-Double blind phase

Reporting group description

Reporting group title

DTG + TDF/FTC-Double blind phase

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

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

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in double blind phase

Subject analysis set title

DTG + 3TC Double blind Phase

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind phase

Subject analysis set title

DTG + 3TC - Double-blind Phase

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 96 weeks in the double blind 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 + 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

Top of page

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 to the nearest whole digit.

End point type

Primary

End point timeframe

Week 48

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[1]	358 ^[2]
Units: Percentage of participants
number (confidence interval 95%)	90 (86.8 to 93.0)	93 (90.0 to 95.4)

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 (<=versus [vs.]>100,000 c/mL) and cluster of differentiation 4+ (CD4+) cell count (<= vs. >200 cells per cubic millimeter).

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

^[3]

Method

Parameter type

Adjusted difference in proportion

Point estimate

-2.6

Confidence interval

level

95%

sides

2-sided

lower limit

-6.7

upper limit

1.5

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 greater than -10%.

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

Top of page

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 Cochran-Mantel-Haenszel weights. Percentage values are rounded to the nearest whole digit.

End point type

Secondary

End point timeframe

Week 24

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[4]	358 ^[5]
Units: Percentage of participants
number (confidence interval 95%)	92 (89.7 to 95.2)	93 (90.4 to 95.7)

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 per cubic millimeter

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Adjusted difference in proportion

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-4.2

upper limit

3.4

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

Top of page

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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[6]	358 ^[7]
Units: Percentage of participants
number (confidence interval 95%)	84 (80.5 to 88.1)	89 (86.2 to 92.6)

Notes
[6] - ITT-E Population
[7] - 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-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Adjusted difference in proportion

Point estimate

-4.9

Confidence interval

level

95%

sides

2-sided

lower limit

-9.8

upper limit

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

Top of page

End point title

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

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 to the nearest whole digit.

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	356 ^[8]	358 ^[9]
Units: Percentage of participants
number (confidence interval 95%)	79 (74.7 to 83.2)	83 (78.8 to 86.6)

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

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Adjusted difference in proportion

Point estimate

-3.6

Confidence interval

level

95%

sides

2-sided

lower limit

-9.4

upper limit

2.1

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

Top of page

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	356 ^[10]	358 ^[11]
Units: Days
median (inter-quartile range (Q1-Q3))	29.0 (29.0 to 53.0)	29.0 (29.0 to 56.0)

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

714

Analysis specification

Pre-specified

Analysis type

^[12]

P-value

= 0.658 ^[13]

Method

Generalized Wilcoxon procedure

Parameter type

Hazard ratio (HR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.16

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

Top of page

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+. It was evaluated 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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[14]	358 ^[15]
Units: Cells/mm^3
arithmetic mean (standard deviation)
Week 24, n=340,341	655.3 ( 288.32 )	632.8 ( 262.61 )
Week 48, n=324,334	687.7 ( 275.47 )	675.3 ( 274.46 )

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

No statistical analyses for this end point

Secondary: CD4+ Cell Counts at Week 96

Top of page

End point title

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. 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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	301 ^[16]	320 ^[17]
Units: Cells per cubic millimeter (cells/mm^3)
arithmetic mean (standard deviation)	732.8 ( 298.05 )	711.5 ( 284.15 )

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

No statistical analyses for this end point

Secondary: CD4+ Cell Counts at Week 144

Top of page

End point title

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. 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	270 ^[18]	287 ^[19]
Units: Cells per cubic millimeter (cells/mm^3)
arithmetic mean (standard deviation)	767.8 ( 274.00 )	758.2 ( 285.35 )

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

Top of page

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+. It was evaluated by flow cytometry. Baseline value is defined as the the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value 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 (represented by n=x in the category titles).

End point type

Secondary

End point timeframe

Baseline (Day 1) and Weeks 24, 48

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[20]	358 ^[21]
Units: Cells per cubic millimeter
arithmetic mean (standard error)
Week 24, n=340,341	192.2 ( 9.67 )	175.1 ( 9.41 )
Week 48, n=324,334	222.2 ( 9.87 )	217.7 ( 10.64 )

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

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-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.754

Method

Mixed Model Repeated Measures (MMRM)

Parameter type

Mean difference (net)

Point estimate

4.6

Confidence interval

level

95%

sides

2-sided

lower limit

-23.9

upper limit

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-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.206

Method

Mixed Model Repeated Measures (MMRM)

Parameter type

Mean difference (net)

Point estimate

17.1

Confidence interval

level

95%

sides

2-sided

lower limit

-9.4

upper limit

43.6

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

Top of page

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 (Day 1). Change from Baseline was defined as post-dose visit value 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 (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	270 ^[22]	287 ^[23]
Units: Cells per cubic millimeter
arithmetic mean (standard error)	301.8 ( 11.51 )	303.2 ( 12.13 )

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

557

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.934

Method

Mixed Model Repeated Measures (MMRM)

Parameter type

Mean difference (net)

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-34.2

upper limit

31.5

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

Top of page

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 (Day 1). Change from Baseline was defined as post-dose visit value 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 (Day 1) and Week 96

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	301 ^[24]	320 ^[25]
Units: Cells/mm^3
arithmetic mean (standard error)	264.7 ( 11.32 )	253.8 ( 11.40 )

Notes
[24] - ITT-E Population.
[25] - 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-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

621

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5

Method

Mixed Model Repeated Measures (MMRM)

Parameter type

Mean difference (net)

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-20.7

upper limit

42.4

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

Top of page

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.

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	356 ^[26]	358 ^[27]
Units: Participants
No HIV-1 disease progression	352	356
From CDC Stage 1 to CDC Stage 3 Event	0	0
From CDC Stage 2 to CDC Stage 3 Event	2	2
From CDC Stage 3 to New CDC Stage 3 Event	1	0
From CDC Stage 1, 2 or 3 to Death	1	0

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

Top of page

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

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	8 ^[28]	8 ^[29]
Units: Participants
INSTI Mutations	0	0
Major mutations of 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 meet 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 was interpreted through a proprietary algorithm (from Monogram Biosciences) and provides the overall susceptibility of the drug. Partially sensitive and resistant calls 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).

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	5 ^[30]	6 ^[31]
Units: Participants
INSTI, DTG, Sensitive, n=,5,4	5	4
INSTI, DTG, Resistant, n=5,4	0	0
INSTI, EGV, Sensitive, n=5,4	5	4
INSTI, EGV, Resistant, n=5,4	0	0
INSTI, RAL, Sensitive, n=5,4	5	4
INSTI, RAL, Resistant, n=5,4	0	0
NRTI, 3TC, Sensitive, n=5,5	5	5
NRTI, 3TC, Resistant, n=5,5	0	0
NRTI, ABC, Sensitive, n=5,5	5	5
NRTI, ABC, Resistant, n=5,5	0	0
NRTI, AZT, Sensitive, n=5,5	5	5
NRTI, AZT, Resistant, n=5,5	0	0
NRTI, D4T, Sensitive, n=5,5	5	5
NRTI, D4T, Resistant, n=5,5	0	0
NRTI, DDI, Sensitive, n=5,5	5	5
NRTI, DDI, Resistant, n=5,5	0	0
NRTI, FTC, Sensitive, n=5,5	5	5
NRTI, FTC, Resistant, n=5,5	0	0
NRTI, TDF, Sensitive, n=5,5	5	5
NRTI, TDF, Resistant, n=5,5	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

Top of page

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. Safety Population was used which comprised of all participants who received at least one dose of study treatment.

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	356 ^[32]	358 ^[33]
Units: Participants
Any AE	307	316
Any SAE	37	38

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 144

Top of page

End point title

Number of Participants With AEs by Maximum Severity Grades up to Week 144

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 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	356 ^[34]	358 ^[35]
Units: Participants
Grade 1 AEs	33	35
Grade 2 AEs	229	242
Grade 3 AEs	37	34
Grade 4 AEs	7	5
Grade 5 AEs	1	0

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 144

Top of page

End point title

Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade up to Week 144

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 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	356 ^[36]	358 ^[37]
Units: Participants
Any drug related AE	77	101
Drug related AEs with maximum toxicity Grade 1	51	70
Drug related AEs with maximum toxicity Grade 2	19	28
Drug related AEs with maximum toxicity Grade 3	7	3
Drug related AEs with maximum toxicity Grade 4	0	0
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

Top of page

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 platelets. 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	356 ^[38]	358 ^[39]
Units: Participants
Hemoglobin, Grades 1 to 4	9	7
Hemoglobin, Grades 2 to 4	1	1
Hemoglobin, Grades 3 to 4	0	0
Hemoglobin, Grade 1	8	6
Hemoglobin, Grade 2	1	1
Hemoglobin, Grade 3	0	0
Hemoglobin, Grade 4	0	0
Leukocytes, Grades 1 to 4	16	3
Leukocytes, Grades 2 to 4	4	2
Leukocytes, Grades 3 to 4	0	0
Leukocytes, Grade 1	12	1
Leukocytes, Grade 2	4	2
Leukocytes, Grade 3	0	0
Leukocytes, Grade 4	0	0
Neutrophils, Grades 1 to 4	25	18
Neutrophils, Grades 2 to 4	19	11
Neutrophils, Grades 3 to 4	7	6
Neutrophils, Grade 1	6	7
Neutrophils, Grade 2	12	5
Neutrophils, Grade 3	5	5
Neutrophils, Grade 4	2	1
Platelets, Grades 1 to 4	14	11
Platelets, Grades 2 to 4	8	4
Platelets, Grades 3 to 4	1	1
Platelets, Grade 1	6	7
Platelets, Grade 2	7	3
Platelets, Grade 3	0	1
Platelets, Grade 4	1	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

Top of page

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) from creatinine adjusted for body surface area (BSA), 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	356 ^[40]	358 ^[41]
Units: Participants
ALT, Grades 1 to 4	55	81
ALT, Grades 2 to 4	23	25
ALT, Grades 3 to 4	14	9
ALT, Grade 1	32	56
ALT, Grade 2	9	16
ALT, Grade 3	7	4
ALT, Grade 4	7	5
Albumin, Grades 1 to 4	1	1
Albumin, Grades 2 to 4	1	0
Albumin, Grades 3 to 4	0	0
Albumin, Grade 1	0	1
Albumin, Grade 2	1	0
Albumin, Grade 3	0	0
Albumin, Grade 4	0	0
ALP, Grades 1 to 4	8	10
ALP, Grades 2 to 4	3	1
ALP, Grades 3 to 4	0	0
ALP, Grade 1	5	9
ALP, Grade 2	3	1
ALP, Grade 3	0	0
ALP, Grade 4	0	0
AST, Grades 1 to 4	52	79
AST, Grades 2 to 4	27	31
AST, Grades 3 to 4	8	13
AST, Grade 1	25	48
AST, Grade 2	19	18
AST, Grade 3	6	9
AST, Grade 4	2	4
Bilirubin, Grades 1 to 4	42	51
Bilirubin, Grades 2 to 4	14	17
Bilirubin, Grades 3 to 4	4	4
Bilirubin, Grade 1	28	34
Bilirubin, Grade 2	10	13
Bilirubin, Grade 3	2	4
Bilirubin, Grade 4	2	0
CO2, Grades 1 to 4	126	116
CO2, Grades 2 to 4	8	9
CO2, Grades 3 to 4	0	0
CO2, Grade 1	118	107
CO2, Grade 2	8	9
CO2, Grade 3	0	0
CO2, Grade 4	0	0
Cholesterol, Grades 1 to 4	77	40
Cholesterol, Grades 2 to 4	24	13
Cholesterol, Grades 3 to 4	0	1
Cholesterol, Grade 1	53	27
Cholesterol, Grade 2	24	12
Cholesterol, Grade 3	0	1
Cholesterol, Grade 4	0	0
CK, Grades 1 to 4	76	75
CK, Grades 2 to 4	43	52
CK, Grades 3 to 4	26	36
CK, Grade 1	33	23
CK, Grade 2	17	16
CK, Grade 3	15	21
CK, Grade 4	11	15
Creatinine, Grades 1 to 4	21	31
Creatinine, Grades 2 to 4	1	3
Creatinine, Grades 3 to 4	0	2
Creatinine, Grade 1	20	28
Creatinine, Grade 2	1	1
Creatinine, Grade 3	0	2
Creatinine, Grade 4	0	0
Direct Bilirubin, Grades 1 to 4	14	13
Direct Bilirubin, Grades 2 to 4	14	13
Direct Bilirubin, Grades 3 to 4	14	13
Direct Bilirubin, Grade 1	0	0
Direct Bilirubin, Grade 2	0	0
Direct Bilirubin, Grade 3	14	13
Direct Bilirubin, Grade 4	0	0
GFR frm creatinine adjusted for BSA Grades 1 to 4	185	226
GFR from creatinine adjusted for BSA Grades 2 to 4	185	226
GFR from creatinine adjusted for BSA Grades 3 to 4	13	27
GFR from creatinine adjusted for BSA, Grade 1	0	0
GFR from creatinine adjusted for BSA, Grade 2	172	199
GFR from creatinine adjusted for BSA Grades 3	13	25
GFR from creatinine adjusted for BSA, Grade 4	0	2
Hypercalcaemia, Grades 1 to 4	7	4
Hypercalcaemia, Grades 2 to 4	0	0
Hypercalcaemia, Grades 3 to 4	0	0
Hypercalcaemia, Grade 1	7	4
Hypercalcaemia, Grade 2	0	0
Hypercalcaemia, Grade 3	0	0
Hypercalcaemia, Grade 4	0	0
Hyperglycemia, Grades 1 to 4	91	81
Hyperglycemia, Grades 2 to 4	38	25
Hyperglycemia, Grades 3 to 4	3	2
Hyperglycemia, Grade 1	53	56
Hyperglycemia, Grade 2	35	23
Hyperglycemia, Grade 3	3	2
Hyperglycemia, Grade 4	0	0
Hyperkalemia, Grades 1 to 4	1	4
Hyperkalemia, Grades 2 to 4	0	1
Hyperkalemia, Grades 3 to 4	0	1
Hyperkalemia, Grade 1	1	3
Hyperkalemia, Grade 2	0	0
Hyperkalemia, Grade 3	0	0
Hyperkalemia, Grade 4	0	1
Hypernatremia, Grades 1 to 4	6	3
Hypernatremia, Grades 2 to 4	0	0
Hypernatremia, Grades 3 to 4	0	0
Hypernatremia, Grade 1	6	3
Hypernatremia, Grade 2	0	0
Hypernatremia, Grade 3	0	0
Hypernatremia, Grade 4	0	0
Hypocalcaemia, Grades 1 to 4	14	13
Hypocalcaemia, Grades 2 to 4	4	3
Hypocalcaemia, Grades 3 to 4	0	1
Hypocalcaemia, Grade 1	10	10
Hypocalcaemia, Grade 2	4	2
Hypocalcaemia, Grade 3	0	1
Hypocalcaemia, Grade 4	0	0
Hypoglycemia, Grades 1 to 4	22	17
Hypoglycemia, Grades 2 to 4	8	3
Hypoglycemia, Grades 3 to 4	2	1
Hypoglycemia, Grade 1	14	14
Hypoglycemia, Grade 2	6	2
Hypoglycemia, Grade 3	1	0
Hypoglycemia, Grade 4	1	1
Hypokalemia, Grades 1 to 4	6	7
Hypokalemia, Grades 2 to 4	0	1
Hypokalemia, Grades 3 to 4	0	0
Hypokalemia, Grade 1	6	6
Hypokalemia, Grade 2	0	1
Hypokalemia, Grade 3	0	0
Hypokalemia, Grade 4	0	0
Hyponatremia, Grades 1 to 4	25	28
Hyponatremia, Grades 2 to 4	2	0
Hyponatremia, Grades 3 to 4	0	0
Hyponatremia, Grade 1	23	28
Hyponatremia, Grade 2	2	0
Hyponatremia, Grade 3	0	0
Hyponatremia, Grade 4	0	0
LDL Cholesterol, Grades 1 to 4	57	35
LDL Cholesterol, Grades 2 to 4	17	14
LDL Cholesterol, Grades 3 to 4	5	4
LDL Cholesterol, Grade 1	40	21
LDL Cholesterol, Grade 2	12	10
LDL Cholesterol, Grade 3	5	4
LDL Cholesterol, Grade 4	0	0
Lactate Dehydrogenase, Grades 1 to 4	3	5
Lactate Dehydrogenase, Grades 2 to 4	0	1
Lactate Dehydrogenase, Grades 3 to 4	0	0
Lactate Dehydrogenase, Grade 1	3	4
Lactate Dehydrogenase, Grade 2	0	1
Lactate Dehydrogenase, Grade 3	0	0
Lactate Dehydrogenase, Grade 4	0	0
Lipase, Grades 1 to 4	65	80
Lipase, Grades 2 to 4	35	49
Lipase, Grades 3 to 4	10	18
Lipase, Grade 1	30	31
Lipase, Grade 2	25	31
Lipase, Grade 3	8	10
Lipase, Grade 4	2	8
Phosphate, Grades 1 to 4	70	68
Phosphate, Grades 2 to 4	35	47
Phosphate, Grades 3 to 4	2	6
Phosphate, Grade 1	35	21
Phosphate, Grade 2	33	41
Phosphate, Grade 3	2	6
Phosphate, Grade 4	0	0
Triglycerides, Grades 1 to 4	80	62
Triglycerides, Grades 2 to 4	12	14
Triglycerides, Grades 3 to 4	7	3
Triglycerides, Grade 1	68	48
Triglycerides, Grade 2	5	11
Triglycerides, Grade 3	6	2
Triglycerides, Grade 4	1	1

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 Week 144

Top of page

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	356 ^[42]	358 ^[43]
Units: Participants	18	17

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 Weeks 24, 48, 96

Top of page

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 Week 24, Week 48 and Week 96

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[44]	358 ^[45]
Units: Participants
Up to Week 24	6	4
Up to Week 48	7	8
Up to Week 96	14	11

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 were collected to perform evaluation of renal inflammation biomarkers which included Serum Cystatin C and Serum Retinol Binding Protein (RBP). Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. 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), presence of diabetes mellitus (factor), presence of hypertension (factor), 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 (Day 1) and at Weeks 24, 48

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[46]	358 ^[47]
Units: Milligrams per Liter (mg/L)
arithmetic mean (standard error)
Serum Cystatin C, Week 24, n=338, 336	-0.05 ( 0.007 )	-0.03 ( 0.007 )
Serum Cystatin C, Week 48, n=324, 332	-0.07 ( 0.007 )	-0.04 ( 0.006 )
Serum RBP, Week 24, n=332, 334	1.6 ( 0.41 )	1.9 ( 0.51 )
Serum RBP, Week 48, n=322, 332	0.5 ( 0.47 )	0.6 ( 0.46 )

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

Statistical Analysis 1

Statistical analysis description

Serum Cystatin C, Week 24

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.025

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04

upper limit

Statistical Analysis 3

Statistical analysis description

Serum RBP, Week 24

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.683

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

Statistical Analysis 4

Statistical analysis description

Serum RBP, Week 48

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.93

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

1.2

Statistical Analysis 2

Statistical analysis description

Serum Cystatin C, Week 48

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

-0.01

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

Top of page

End point title

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

End point description

Blood samples were collected to perform evaluation of renal biomarkers which included Serum Cystatin C. Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value 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 (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	283 ^[48]	298 ^[49]
Units: Milligrams per Liter (mg/L)
arithmetic mean (standard error)	-0.12 ( 0.006 )	-0.11 ( 0.007 )

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

581

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.108

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

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

Top of page

End point title

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

End point description

Blood samples were collected to perform evaluation of renal inflammation biomarkers which included Serum Cystatin C. Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. 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), presence of diabetes mellitus (factor), presence of hypertension (factor), 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 (Day 1) and at Week 96

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	300 ^[50]	319 ^[51]
Units: Milligrams per Liter (mg/L)
arithmetic mean (standard error)	-0.11 ( 0.006 )	-0.09 ( 0.006 )

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

Statistical Analysis

Statistical analysis description

Week 96. Serum Cystatin C.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

619

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.009

Method

Mixed Model Repeated Measures

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

Top of page

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 (Day 1). Change from Baseline was defined as post-dose visit value 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 (Day 1) and at Week 96

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	288 ^[52]	310 ^[53]
Units: Microgram per millimoles (ug/mmol)
arithmetic mean (standard deviation)	1.535 ( 8.5872 )	7.704 ( 41.9650 )

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 (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	276 ^[54]	292 ^[55]
Units: Microgram per millimoles (ug/mmol)
arithmetic mean (standard deviation)	1.760 ( 5.7909 )	8.855 ( 35.5147 )

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

Top of page

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 &/or urine collected for evaluation of renal inflammation biomarkers: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 (Day 1). Change from Baseline was post-dose visit value minus Baseline value.Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor),age,sex (factor),race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, baseline biomarker value& 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 (Day 1) and at Weeks 24, 48

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[56]	358 ^[57]
Units: Milliliter/minute/1.73*meter^2
arithmetic mean (standard error)
GFR-cystatin C adjusted, Week 24, n=338, 336	4.4 ( 0.63 )	2.2 ( 0.60 )
GFR-cystatin C adjusted, Week 48, n=324, 332	7.0 ( 0.60 )	4.1 ( 0.59 )
GFR-creatinine adjusted, Week 24, n=340, 341	-13.5 ( 0.59 )	-16.7 ( 0.56 )
GFR-creatinine adjusted, Week 48, n=326,335	-12.1 ( 0.56 )	-15.6 ( 0.55 )

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

Statistical Analysis 1

Statistical analysis description

GFR-cystatin C adjusted, Week 24

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

P-value

= 0.011

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

2.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

Statistical Analysis 4

Statistical analysis description

GFR- creatinine adjusted, Week 48

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

3.5

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

5.1

Statistical Analysis 3

Statistical analysis description

GFR-creatinine adjusted, Week 24

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

3.2

Confidence interval

level

95%

sides

2-sided

lower limit

1.6

upper limit

4.8

Statistical Analysis 2

Statistical analysis description

GFR-cystatin C adjusted, Week 48

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

2.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

4.5

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

Top of page

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 (Day 1). Change from Baseline was defined as post-dose visit value 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 (Day 1) and at Week 96

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	300 ^[58]	319 ^[59]
Units: Milliliter/minute/1.73*meter^2
arithmetic mean (standard deviation)
GFR Cystatin C adjusted, Week 96	11.3 ( 14.54 )	9.3 ( 13.78 )
GFR creatinine adjusted, Week 96	-15.3 ( 11.50 )	-19.0 ( 11.25 )

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

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Blood &/or urine were for evaluation of renal inflammation biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean & 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), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction,baseline biomarker value & 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 (Day 1) and at Weeks 24, 48

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[60]	358 ^[61]
Units: Micromoles per Liter (umol/L)
arithmetic mean (standard error)
Serum or Plasma Creatinine, Week 24, n=340, 343	11.88 ( 0.510 )	15.07 ( 0.520 )
Serum or Plasma Creatinine, Week 48, n=326, 335	10.39 ( 0.466 )	13.61 ( 0.480 )

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

Statistical Analysis 1

Statistical analysis description

Week 24

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-3.19

Confidence interval

level

95%

sides

2-sided

lower limit

-4.62

upper limit

-1.75

Statistical Analysis 2

Statistical analysis description

Week 48

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-3.22

Confidence interval

level

95%

sides

2-sided

lower limit

-4.54

upper limit

-1.91

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

Top of page

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 (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	356 ^[62]	358 ^[63]
Units: Milliliter/minute/1.73*meter^2
arithmetic mean (standard deviation)
GFR Cystatin C adjusted, Week 144, n=283,298	13.0 ( 13.64 )	12.1 ( 15.24 )
GFR creatinine adjusted, Week 144, n=271, 289	-16.7 ( 11.65 )	-19.3 ( 11.07 )

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

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

Blood and/or urine were collected to perform evaluation of renal inflammation biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was calculated as post-dose visit value minus Baseline value. 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), presence of diabetes mellitus (factor), presence of hypertension (factor), 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 (Day 1) and at Week 96

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	300 ^[64]	319 ^[65]
Units: Micromoles per Liter (umol/L)
arithmetic mean (standard error)	12.75 ( 0.623 )	16.10 ( 0.539 )

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

Statistical Analysis

Statistical analysis description

Week 96. Serum or Plasma creatinine

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

619

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-3.34

Confidence interval

level

95%

sides

2-sided

lower limit

-4.96

upper limit

-1.72

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

Top of page

End point title

Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine 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	271 ^[66]	289 ^[67]
Units: Micromoles per Liter (umol/L)
arithmetic mean (standard error)	12.89 ( 0.583 )	15.87 ( 0.560 )

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

560

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-2.98

Confidence interval

level

95%

sides

2-sided

lower limit

-4.57

upper limit

-1.4

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

Top of page

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 which included 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 is defined as the latest pre-dose assessment (Day 1). Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Statistical analysis of changes from baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios. Estimated ratio of geometric means (each visit over Baseline) and 95% confidence interval (CI) have been 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 Weeks 24, 48

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[68]	358 ^[69]
Units: Ratio
geometric mean (confidence interval 95%)
Serum B2M, Week 24, n=338, 335	0.798 (0.779 to 0.817)	0.872 (0.856 to 0.890)
Serum B2M, Week 48, n=324, 332	0.806 (0.790 to 0.823)	0.892 (0.876 to 0.908)
Urine B2M, Week 24, n=121, 95	0.887 (0.756 to 1.039)	1.351 (1.060 to 1.722)
Urine B2M, Week 48, n=119, 103	0.900 (0.792 to 1.022)	1.338 (1.148 to 1.560)
Urine Albumin/Creatinine, Week 24, n=254, 252	1.014 (0.927 to 1.109)	1.050 (0.964 to 1.144)
Urine Albumin/Creatinine , Week 48, n=237, 244	0.934 (0.857 to 1.017)	1.048 (0.968 to 1.134)
Urine B2M/Urine Creatinine, Week 24, n=121, 95	0.852 (0.737 to 0.985)	1.331 (1.071 to 1.655)
Urine B2M/Urine Creatinine, Week 48, n=114, 100	0.888 (0.777 to 1.015)	1.278 (1.119 to 1.458)
Urine Phosphate, Week 24, n=330, 332	1.115 (1.025 to 1.212)	1.012 (0.934 to 1.095)
Urine Phosphate, Week 48, n=316, 330	1.061 (0.983 to 1.145)	1.075 (0.996 to 1.159)
Urine Protein/Creatinine , Week 24, n=269, 265	0.850 (0.806 to 0.895)	1.016 (0.960 to 1.075)
Urine Protein/Creatinine , Week 48, n=252, 269	0.879 (0.838 to 0.922)	1.061 (1.009 to 1.115)
Urine RBP 4, Week 24, n=332, 330	0.934 (0.842 to 1.036)	1.073 (0.951 to 1.209)
Urine RBP 4, Week 48, n=318, 328	1.115 (1.009 to 1.233)	1.490 (1.332 to 1.667)
Urine RBP 4/Urine Creatinine , Week 24, n=329, 330	0.919 (0.846 to 0.998)	1.110 (1.003 to 1.228)
Urine RBP 4/Urine Creatinine , Week 48, n=304, 318	1.147 (1.060 to 1.241)	1.500 (1.367 to 1.646)

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

Statistical Analysis 1

Statistical analysis description

Week 24. Serum B2M

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.915

Confidence interval

level

95%

sides

2-sided

lower limit

0.887

upper limit

0.943

Statistical Analysis 2

Statistical analysis description

Week 48. Serum B2M

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.904

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

0.929

Statistical Analysis 9

Statistical analysis description

Week 24. Urine Phosphate

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.099

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

1.102

Confidence interval

level

95%

sides

2-sided

lower limit

0.982

upper limit

1.237

Statistical Analysis 8

Statistical analysis description

Week 48. Urine B2M/Urine Creatinine

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.695

Confidence interval

level

95%

sides

2-sided

lower limit

0.576

upper limit

0.839

Statistical Analysis 7

Statistical analysis description

Week 24. Urine B2M/Urine Creatinine

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.493

upper limit

0.831

Statistical Analysis 6

Statistical analysis description

Week 48. Urine Albumin/Creatinine

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.051

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.891

Confidence interval

level

95%

sides

2-sided

lower limit

0.793

upper limit

1.001

Statistical Analysis 5

Statistical analysis description

Week 24. Urine Albumin/Creatinine

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.575

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.965

Confidence interval

level

95%

sides

2-sided

lower limit

0.853

upper limit

1.092

Statistical Analysis 4

Statistical analysis description

Week 48. Urine B2M

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.672

Confidence interval

level

95%

sides

2-sided

lower limit

0.551

upper limit

0.821

Statistical Analysis 3

Statistical analysis description

Week 24. Urine B2M

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.005

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.656

Confidence interval

level

95%

sides

2-sided

lower limit

0.491

upper limit

0.877

Statistical Analysis 14

Statistical analysis description

Week 48. Urine RBP 4

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.748

Confidence interval

level

95%

sides

2-sided

lower limit

0.644

upper limit

0.87

Statistical Analysis 13

Statistical analysis description

Week 24. Urine RBP 4

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.087

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.871

Confidence interval

level

95%

sides

2-sided

lower limit

0.743

upper limit

1.02

Statistical Analysis 12

Statistical analysis description

Week 48. Urine Protein/Creatinine

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.829

Confidence interval

level

95%

sides

2-sided

lower limit

0.773

upper limit

0.888

Statistical Analysis 11

Statistical analysis description

Week 24. Urine Protein/Creatinine

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.836

Confidence interval

level

95%

sides

2-sided

lower limit

0.774

upper limit

0.904

Statistical Analysis 10

Statistical analysis description

Week 48. Urine Phosphate

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.816

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.987

Confidence interval

level

95%

sides

2-sided

lower limit

0.886

upper limit

1.1

Statistical Analysis 15

Statistical analysis description

Week 24. Urine RBP 4/Urine Creatinine

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.005

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.828

Confidence interval

level

95%

sides

2-sided

lower limit

0.727

upper limit

0.944

Statistical Analysis 16

Statistical analysis description

Week 48. Urine RBP 4/Urine Creatinine

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.765

Confidence interval

level

95%

sides

2-sided

lower limit

0.677

upper limit

0.864

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

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 96

End point description

Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers which included Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine. Baseline value is defined as the latest pre-dose assessment (Day 1). Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Statistical analysis of changes from baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios. Estimated ratio of geometric means (each visit over Baseline) and 95% confidence interval (CI) have been 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 Week 96

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[70]	358 ^[71]
Units: Ratio
geometric mean (confidence interval 95%)
Urine Albumin/Creatinine, Week 96, n=222, 243	0.924 (0.847 to 1.008)	1.101 (1.008 to 1.202)
Urine B2M/Urine Creatinine , Week 96, n=107, 104	0.794 (0.720 to 0.877)	1.441 (1.193 to 1.740)
Urine Phosphate, Week 96, n=292, 316	1.113 (1.021 to 1.214)	1.066 (0.984 to 1.155)
Urine Protein/Creatinine, Week 96, n=238, 258	0.868 (0.818 to 0.920)	1.053 (1.004 to 1.105)
Urine RBP 4/Urine Creatinine, Week 96, n=289, 311	1.310 (1.207 to 1.420)	1.771 (1.604 to 1.955)

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

Statistical Analysis 1

Statistical analysis description

Week 96. Urine Albumin/Creatinine.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.006

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.839

Confidence interval

level

95%

sides

2-sided

lower limit

0.742

upper limit

0.95

Statistical Analysis 2

Statistical analysis description

Week 96. Urine B2M/Urine Creatinine.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.551

Confidence interval

level

95%

sides

2-sided

lower limit

0.445

upper limit

0.682

Statistical Analysis 5

Statistical analysis description

Week 96. Urine RBP 4/Urine Creatinine

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.651

upper limit

0.84

Statistical Analysis 4

Statistical analysis description

Week 96. Urine Protein/Creatinine.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.824

Confidence interval

level

95%

sides

2-sided

lower limit

0.764

upper limit

0.889

Statistical Analysis 3

Statistical analysis description

Week 96. Urine Phosphate.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.467

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

1.045

Confidence interval

level

95%

sides

2-sided

lower limit

0.928

upper limit

1.175

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 (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	356 ^[72]	358 ^[73]
Units: Ratio
geometric mean (confidence interval 95%)
Urine Albumin/Creatinine , Week 144, n=207, 212	1.050 (0.954 to 1.155)	1.146 (1.039 to 1.264)
Urine B2M/Urine Creatinine , Week 144, n=100, 102	0.751 (0.679 to 0.830)	1.518 (1.281 to 1.799)
Urine Phosphate, Week 144, n=274, 294	1.040 (0.954 to 1.133)	0.955 (0.879 to 1.037)
Urine Protein/Creatinine , Week 144, n=225,232	0.988 (0.932 to 1.047)	1.210 (1.144 to 1.280)
Urine RBP 4/Urine Creatinine, Week 144, n=276, 292	1.648 (1.550 to 1.752)	2.425 (2.208 to 2.663)

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

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

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.205

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.916

Confidence interval

level

95%

sides

2-sided

lower limit

0.799

upper limit

1.05

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

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.495

Confidence interval

level

95%

sides

2-sided

lower limit

0.406

upper limit

0.603

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

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.16

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

1.089

Confidence interval

level

95%

sides

2-sided

lower limit

0.967

upper limit

1.226

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

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.817

Confidence interval

level

95%

sides

2-sided

lower limit

0.753

upper limit

0.885

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

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Ratio of geometric means

Point estimate

0.679

Confidence interval

level

95%

sides

2-sided

lower limit

0.607

upper limit

0.76

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. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was calculated as post-dose visit value minus Baseline value. 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. 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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[74]	358 ^[75]
Units: Micrograms per Liter (ug/L)
arithmetic mean (standard error)
Bone-ALP, Week 24, n=334, 332	0.91 ( 0.179 )	3.13 ( 0.199 )
Bone-ALP, Week 48, n=321, 331	1.21 ( 0.193 )	3.79 ( 0.239 )
Serum Osteocalcin, Week 24, n=335, 334	2.56 ( 0.341 )	6.74 ( 0.347 )
Serum Osteocalcin, Week 48, n=322, 330	0.78 ( 0.311 )	6.01 ( 0.400 )
PINP, Week 24, n=337, 336	4.5 ( 0.91 )	18.3 ( 1.06 )
PINP, Week 48, n=321, 334	0.5 ( 0.83 )	13.1 ( 0.84 )
CTX-1, Week 24, n=337, 334	0.1192 ( 0.01304 )	0.2820 ( 0.01472 )
CTX-1, Week 48, n=323, 331	0.1338 ( 0.01258 )	0.3352 ( 0.01885 )

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

Statistical Analysis 1

Statistical analysis description

Week 24. Bone ALP

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-2.23

Confidence interval

level

95%

sides

2-sided

lower limit

-2.75

upper limit

-1.7

Statistical Analysis 2

Statistical analysis description

Week 48. Bone ALP

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-2.58

Confidence interval

level

95%

sides

2-sided

lower limit

-3.19

upper limit

-1.98

Statistical Analysis 3

Statistical analysis description

Week 24. Serum Osteocalcin

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-4.19

Confidence interval

level

95%

sides

2-sided

lower limit

-5.15

upper limit

-3.23

Statistical Analysis 8

Statistical analysis description

Week 48. CTX-1

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.2015

Confidence interval

level

95%

sides

2-sided

lower limit

-0.246

upper limit

-0.1569

Statistical Analysis 5

Statistical analysis description

Week 24. Serum PINP

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-13.8

Confidence interval

level

95%

sides

2-sided

lower limit

-16.5

upper limit

-11.1

Statistical Analysis 6

Statistical analysis description

Week 48. Serum PINP

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-12.6

Confidence interval

level

95%

sides

2-sided

lower limit

-15

upper limit

-10.3

Statistical Analysis 7

Statistical analysis description

Week 24. CTX-1

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.1628

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2015

upper limit

-0.1241

Statistical Analysis 4

Statistical analysis description

Week 48. Serum Osteocalcin

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-5.23

Confidence interval

level

95%

sides

2-sided

lower limit

-6.22

upper limit

-4.23

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

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Week 96

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[76]	358 ^[77]
Units: Micrograms per Liter (ug/L)
arithmetic mean (standard error)
Bone-ALP, Week 96, n=296, 317	0.30 ( 0.191 )	2.37 ( 0.216 )
Serum Osteocalcin, Week 96, n=297, 320	0.40 ( 0.345 )	4.57 ( 0.391 )
PINP, Week 96, n=297, 319	15.0 ( 1.63 )	28.3 ( 1.50 )
CTX-1, Week 96, n=297, 315	0.1351 ( 0.01580 )	0.2943 ( 0.01916 )

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

Statistical Analysis 1

Statistical analysis description

Week 96, Bone ALP

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-2.06

Confidence interval

level

95%

sides

2-sided

lower limit

-2.63

upper limit

-1.5

Statistical Analysis 4

Statistical analysis description

Week 96, CTX-1

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.1592

Confidence interval

level

95%

sides

2-sided

lower limit

-0.208

upper limit

-0.1104

Statistical Analysis 3

Statistical analysis description

Week 96, Serum PINP

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-13.3

Confidence interval

level

95%

sides

2-sided

lower limit

-17.6

upper limit

-8.9

Statistical Analysis 2

Statistical analysis description

Week 96, Serum Osteocalcin

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-4.17

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

-3.14

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	356 ^[78]	358 ^[79]
Units: Micrograms per Liter (ug/L)
arithmetic mean (standard error)
Bone-ALP, Week 144, n=281, 295	-0.25 ( 0.172 )	1.43 ( 0.217 )
Serum Osteocalcin, Week 144, n=281, 299	0.29 ( 0.374 )	3.21 ( 0.403 )
PINP, Week 144, n=281,299	4.6 ( 1.04 )	13.8 ( 1.14 )
CTX-1, Week 144, n=281, 296	0.0750 ( 0.01150 )	0.2164 ( 0.01407 )

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

714

Analysis specification

Pre-specified

Analysis type

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-1.68

Confidence interval

level

95%

sides

2-sided

lower limit

-2.23

upper limit

-1.14

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

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-2.91

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

-1.83

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

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-9.2

Confidence interval

level

95%

sides

2-sided

lower limit

-12.3

upper limit

-6.2

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

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-0.1414

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1771

upper limit

-0.1056

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

Blood samples were collected to perform evaluation of bone biomarker serum vitamin D. Baseline value is defined as the latest pre-dose assessment (Day 1). Change from Baseline was calculated as post-dose visit value minus Baseline value. 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. 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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	298 ^[80]	320 ^[81]
Units: Nanomoles per Liter (nmol/L)
arithmetic mean (standard error)	-2.2 ( 1.05 )	0.7 ( 1.04 )

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

Statistical Analysis

Statistical analysis description

Week 96

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

618

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.048

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-5.8

upper limit

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

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24, 48

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[82]	358 ^[83]
Units: Nanomoles per Liter (nmol/L)
arithmetic mean (standard error)
Serum Vitamin D, Week 24, n=337, 337	5.9 ( 1.15 )	12.4 ( 1.33 )
Serum Vitamin D, Week 48, n=322, 333	-3.1 ( 0.89 )	3.1 ( 1.10 )

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

Statistical Analysis 2

Statistical analysis description

Week 48

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-6.2

Confidence interval

level

95%

sides

2-sided

lower limit

-9

upper limit

-3.4

Statistical Analysis 1

Statistical analysis description

Week 24

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-6.5

Confidence interval

level

95%

sides

2-sided

lower limit

-9.9

upper limit

-3

Secondary: Percentage 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 Weeks 24, 48

Top of page

End point title

Percentage 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 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 (Day 1) and at Weeks 24, 48

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[84]	358 ^[85]
Units: Percentage change
arithmetic mean (standard deviation)
Serum or Plasma Cholesterol, Week 24, n=294, 297	9.4 ( 17.44 )	-4.7 ( 16.12 )
Serum or Plasma Cholesterol, Week 48, n=280, 289	10.5 ( 18.89 )	-2.4 ( 17.14 )
HDL Cholesterol, Direct, Week 24, n=294, 297	16.4 ( 22.58 )	3.4 ( 21.55 )
HDL Cholesterol, Direct, Week 48, n=280, 289	15.0 ( 25.07 )	5.0 ( 33.04 )
LDL Cholesterol, Week 24, n=294, 297	12.4 ( 45.05 )	-8.1 ( 23.70 )
LDL Cholesterol, Week 48, n=280, 289	14.8 ( 48.74 )	-4.0 ( 24.06 )
Triglycerides ,Week 24, n=294, 297	8.5 ( 46.57 )	4.3 ( 72.35 )
Triglycerides , Week 48, n=280, 289	12.8 ( 68.99 )	4.4 ( 70.43 )

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

No statistical analyses for this end point

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 (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	281 ^[86]	298 ^[87]
Units: Nanomoles per Liter (nmol/L)
arithmetic mean (standard error)	-2.0 ( 1.16 )	2.9 ( 1.28 )

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

579

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.004

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (net)

Point estimate

-4.9

Confidence interval

level

95%

sides

2-sided

lower limit

-8.3

upper limit

-1.6

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.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Week 96

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	253 ^[88]	277 ^[89]
Units: Millimoles per liter
arithmetic mean (standard error)
Serum or Plasma Cholesterol, Week 96	0.379 ( 0.0376 )	-0.104 ( 0.0378 )
HDL Cholesterol, Direct, Week 96	0.199 ( 0.0156 )	0.090 ( 0.0149 )
LDL Cholesterol, Week 96,	0.147 ( 0.0338 )	-0.154 ( 0.0303 )
Triglycerides, Week 96,	0.129 ( 0.0835 )	-0.112 ( 0.0358 )

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

Top of page

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 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.

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Weeks 24, 48

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[90]	358 ^[91]
Units: Percentage change
arithmetic mean (standard deviation)
Total/HDL Cholesterol Ratio, Week 24, n=294, 297	-4.0 ( 19.08 )	-4.6 ( 27.52 )
Total/HDL Cholesterol Ratio, Week 48, n=280, 289	-0.2 ( 31.10 )	-4.4 ( 16.96 )

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

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	245 ^[92]	256 ^[93]
Units: Millimoles per liter
arithmetic mean (standard error)
Serum or Plasma Cholesterol, Week 144,	0.367 ( 0.0408 )	-0.037 ( 0.0406 )
HDL Cholesterol, Direct, Week 144	0.181 ( 0.0150 )	0.098 ( 0.0147 )
LDL Cholesterol, Week 144,	0.170 ( 0.0336 )	-0.105 ( 0.0348 )
Triglycerides, Week 144	0.117 ( 0.0872 )	-0.104 ( 0.0385 )

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 144

Top of page

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 was defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. 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 (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	245 ^[94]	256 ^[95]
Units: Ratio
arithmetic mean (standard error)	-0.229 ( 0.0559 )	-0.386 ( 0.0463 )

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 96

Top of page

End point title

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

End point description

End point type

Secondary

End point timeframe

Baseline (Day 1) and at Week 96

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	253 ^[96]	277 ^[97]
Units: Ratio
arithmetic mean (standard error)	-0.213 ( 0.0566 )	-0.402 ( 0.0479 )

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

Top of page

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 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 are 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 to the nearest whole digit. 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 Week 48

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[98]	358 ^[99]
Units: Percentage of participants
Week 24, n=309, 316	4	2
Week 48, n=318, 320	4	3

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

Statistical Analysis 1

Statistical analysis description

Week 24

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

P-value

= 0.157 ^[100]

Method

Fisher exact

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

4.6

Notes
[100] - Fisher's exact p-value.

Statistical Analysis 2

Statistical analysis description

Week 48

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.414 ^[101]

Method

Fisher exact

Parameter type

Difference in percentage

Point estimate

1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

4.2

Notes
[101] - Fisher's exact p-value.

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

Top of page

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 for fasting LDL cholesterol. Any abnormalities were evaluated by investigator& 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, 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 to the nearest whole digit. 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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	320 ^[102]	323 ^[103]
Units: Percentage of participants	5	4

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

Statistical Analysis

Statistical analysis description

Week 96

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

643

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.562 ^[104]

Method

Fisher exact

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

4.1

Notes
[104] - Fisher's exact p-value.

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

Top of page

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 to the nearest whole digit. 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	321 ^[105]	322 ^[106]
Units: Percentage of participants	5	4

Notes
[105] - Safety Population.
[106] - 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

643

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.587 ^[107]

Method

Fisher exact

Parameter type

Difference in percentage

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

4.3

Notes
[107] - Fisher's exact p-value.

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

Top of page

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, >200), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian, Other). Percentage values are rounded to the nearest whole digit. 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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[108]	358 ^[109]
Units: Percentage of participants
Baseline CD4+ cell count, <=200,n=31,29	90	86
Baseline CD4+ cell count, >200,n=325,329	93	94
Female, n=59, 52	93	96
Male, n=297, 306	92	92
Age, <35,n= 211, 205	93	95
Age, 35 to <50,n=116, 107	91	93
Age, >=50, n=29, 46	93	85
Baseline plasma HIV-1 RNA, <=100000,n=282,282	93	95
Baseline plasma HIV-1 RNA, >100000,n=74, 76	92	87
Race, White, n=244,247	93	95
Race, African American/African H., n=39, 36	92	81
Race, Asian, n=37, 42	89	93
Race, Other, n=36, 33	94	94

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 48

Top of page

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, >200), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian, Other). Percentage values are rounded to the nearest whole digit. ITT-E Population. 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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[110]	358 ^[111]
Units: Percentage of participants
Baseline CD4+ cell count, <=200,n=31,29	81	90
Baseline CD4+ cell count, >200,n=325,329	91	93
Female, n=59, 52	88	94
Male, n=297, 306	90	92
Age, <35,n= 211, 205	92	93
Age, 35 to <50,n=116, 107	86	94
Age, >=50, n=29, 46	90	87
Baseline plasma HIV-1 RNA, <=100000,n=282,282	90	93
Baseline plasma HIV-1 RNA, >100000,n=74, 76	88	91
Race, White, n=244,247	90	94
Race, African American/African H., n=39, 36	87	81
Race, Asian, n=37, 42	92	98
Race, Other, n=36, 33	89	94

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

Top of page

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 to the nearest whole digit. 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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[112]	358 ^[113]
Units: Percentage of participants
Baseline CD4+ cell count, <=200,n=31, 29	65	90
Baseline CD4+ cell count, >200,n=325,329	86	89
Female, n=59, 52	83	88
Male, n=297,306,	85	90
Age, <35,n= 211, 205	84	90
Age, 35 to <50,n=116, 107	84	89
Age, >=50, n=29,46	86	87
Baseline plasma HIV-1 RNA, <=100000,n=282,282	85	90
Baseline plasma HIV-1 RNA, >100000,n=74, 76	81	88
Race, White, n=244,247	86	90
Race, African American/African H., n=39,36	79	81
Race, Asian, n=37, 42	78	90
Race, Other, n=36, 33	86	91

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

Top of page

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 to the nearest whole digit. 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	356 ^[114]	358 ^[115]
Units: Percentage of participants
Baseline CD4+ cell count, <=200,n=31, 29	58	83
Baseline CD4+ cell count, >200,n=325,329	81	83
Female, n=59, 52	71	85
Male, n=297,306,	80	82
Age, <35,n= 211, 205	77	83
Age, 35 to <50,n=116, 107	81	83
Age, >=50, n=29,46	83	78
Baseline plasma HIV-1 RNA, <=100000,n=282,282	79	82
Baseline plasma HIV-1 RNA, >100000,n=74, 76	78	87
Race, White, n=244,247	82	85
Race, African American/African H., n=39,36	69	72
Race, Asian, n=37, 42	73	81
Race, Other, n=36, 33	78	79

Notes
[114] - ITT-E Population
[115] - 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& as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is latest pre-dose assessment (Day 1). Change from Baseline as post-dose visit value minus Baseline value. Adjusted mean & standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age, Gender, and race). For each subgroup, adjusted mean is estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, treatment & 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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[116]	358 ^[117]
Units: Cells per cubic millimeter
arithmetic mean (standard error)
Baseline plasma HIV-1 RNA,<=100000, n=268,268	187.72 ( 10.860 )	167.93 ( 10.842 )
Baseline plasma HIV-1 RNA,>100000, n=72,73	206.63 ( 21.107 )	205.96 ( 20.990 )
Baseline CD4+ cell count,<=200, n=29,27	157.01 ( 33.113 )	120.17 ( 34.151 )
Baseline CD4+ cell count,>200, n=311, 314	195.11 ( 10.026 )	180.73 ( 9.972 )
Age, <35,n= 203,199	202.76 ( 12.456 )	177.62 ( 12.563 )
Age, 35 to <50, n=109, 100	172.05 ( 16.983 )	179.87 ( 17.733 )
Age, >=50, n=28, 42	188.79 ( 33.534 )	159.34 ( 27.344 )
Female, n=57,50	199.45 ( 23.498 )	181.78 ( 25.263 )
Male, n=283,291	190.21 ( 10.538 )	175.05 ( 10.400 )
Race, White, n=236,235	204.78 ( 11.531 )	182.27 ( 11.582 )
Race, African Am/African H., n=36,33	143.84 ( 29.541 )	170.51 ( 30.870 )
Race, Asian, n=34, 41	169.80 ( 30.491 )	165.36 ( 27.782 )
Race, Other, n=34,32	174.30 ( 30.375 )	149.34 ( 31.404 )

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

Statistical Analysis

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 and treatment and HIV-1 RNA interaction.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

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

-10.23

upper limit

49.83

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 and treatment and HIV-1 RNA interaction.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

-57.07

upper limit

58.4

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

36.84

Confidence interval

level

95%

sides

2-sided

lower limit

-55.94

upper limit

129.63

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

14.37

Confidence interval

level

95%

sides

2-sided

lower limit

-13.38

upper limit

42.12

Statistical Analysis 5

Statistical analysis description

Age<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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

25.14

Confidence interval

level

95%

sides

2-sided

lower limit

-9.56

upper limit

59.85

Statistical Analysis 6

Statistical analysis description

Age 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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-7.82

Confidence interval

level

95%

sides

2-sided

lower limit

-55.98

upper limit

40.34

Statistical Analysis 7

Statistical analysis description

Age>=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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

29.45

Confidence interval

level

95%

sides

2-sided

lower limit

-55.47

upper limit

114.38

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 group, and treatment and race group interaction.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

22.51

Confidence interval

level

95%

sides

2-sided

lower limit

-9.52

upper limit

54.54

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

15.16

Confidence interval

level

95%

sides

2-sided

lower limit

-13.9

upper limit

44.21

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

17.67

Confidence interval

level

95%

sides

2-sided

lower limit

-49.89

upper limit

85.23

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 group, and treatment and race group interaction.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-26.67

Confidence interval

level

95%

sides

2-sided

lower limit

-110.64

upper limit

57.3

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 group, and treatment and race group interaction.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

4.44

Confidence interval

level

95%

sides

2-sided

lower limit

-76.18

upper limit

85.06

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 group, and treatment and race group interaction.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

24.96

Confidence interval

level

95%

sides

2-sided

lower limit

-60.68

upper limit

110.59

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 & as HIV infection progresses,the number of these cells declines.Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is latest pre-dose assessment (Day 1). Change from Baseline was post-dose visit value minus Baseline value. Adjusted mean & 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 estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, treatment & relevant subgroup interaction.For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as 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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[118]	358 ^[119]
Units: Cells per cubic millimeter
arithmetic mean (standard error)
Baseline plasma HIV-1 RNA,<=100000, n=257,264	220.0 ( 11.72 )	212.4 ( 11.56 )
Baseline plasma HIV-1 RNA,>100000, n=67,70	238.5 ( 23.09 )	235.5 ( 22.70 )
Baseline CD4+ cell count,<=200, n=26, 27	200.5 ( 36.97 )	177.9 ( 36.18 )
Baseline CD4+ cell count,>200, n=298, 307	225.9 ( 10.84 )	220.7 ( 10.68 )
Age group-1, <35,n= 194, 192	233.6 ( 13.49 )	225.2 ( 13.53 )
Age group-1, 35 to <50, n=104, 101	208.7 ( 18.40 )	211.2 ( 18.67 )
Age group-1, >=50, n=26, 41	212.6 ( 36.84 )	194.8 ( 29.27 )
Female, n=54, 49	237.1 ( 25.53 )	226.8 ( 26.98 )
Male, n=270, 285	221.2 ( 11.41 )	215.6 ( 11.11 )
Race, White, n=224, 231	226.0 ( 12.55 )	219.7 ( 12.39 )
Race, African Am/African H., n=33, 31	209.8 ( 32.75 )	239.9 ( 33.79 )
Race, Asian, n=34, 41	246.4 ( 32.35 )	197.2 ( 29.47 )
Race, Other, n=33, 31	200.2 ( 32.69 )	202.7 ( 33.83 )

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

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 and treatment and HIV-1 RNA interaction.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-59.8

upper limit

65.9

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 and treatment and HIV-1 RNA interaction.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

7.6

Confidence interval

level

95%

sides

2-sided

lower limit

-24.6

upper limit

39.8

Statistical Analysis 6

Statistical analysis description

Age 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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-53.9

upper limit

48.9

Statistical Analysis 5

Statistical analysis description

Age<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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

8.4

Confidence interval

level

95%

sides

2-sided

lower limit

-29.1

upper limit

45.9

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

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

-24.7

upper limit

35.1

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

22.6

Confidence interval

level

95%

sides

2-sided

lower limit

-78.3

upper limit

123.5

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 group, and treatment and race group interaction

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

49.2

Confidence interval

level

95%

sides

2-sided

lower limit

-36.3

upper limit

134.7

Statistical Analysis 11

Statistical analysis description

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-30.2

Confidence interval

level

95%

sides

2-sided

lower limit

-122.7

upper limit

62.4

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 group, and treatment and race group interaction.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

6.3

Confidence interval

level

95%

sides

2-sided

lower limit

-28.2

upper limit

40.9

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

5.6

Confidence interval

level

95%

sides

2-sided

lower limit

-25.6

upper limit

36.9

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-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (net)

Point estimate

10.4

Confidence interval

level

95%

sides

2-sided

lower limit

-62.3

upper limit

83.1

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 group, and treatment and race group interaction.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (net)

Point estimate

-2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-94.7

upper limit

89.7

Statistical Analysis 7

Statistical analysis description

Age>=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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

17.7

Confidence interval

level

95%

sides

2-sided

lower limit

-74.6

upper limit

110.1

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 & as HIV infection progresses,the number of these cells declines.Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is latest pre-dose assessment (Day 1). Change from Baseline was post-dose visit value minus Baseline value. Adjusted mean & 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 estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, treatment & relevant subgroup interaction.For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as 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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[120]	358 ^[121]
Units: Cells per cubic millimeter
arithmetic mean (standard error)
Baseline plasma HIV-1 RNA,<=100000, n=240,253	254.8 ( 13.30 )	252.9 ( 12.93 )
Baseline plasma HIV-1 RNA,>100000, n=61,67	300.2 ( 26.50 )	260.1 ( 25.42 )
Baseline CD4+ cell count,<=200, n=21,26	240.5 ( 45.16 )	244.4 ( 40.44 )
Baseline CD4+ cell count,>200, n=280,294	265.9 ( 12.28 )	255.1 ( 11.98 )
Age group-1, <35,n= 179,185	270.2 ( 15.38 )	263.0 ( 15.09 )
Age group-1, 35 to <50, n=97,95	259.5 ( 20.86 )	262.0 ( 21.09 )
Age group-1, >=50, n=25, 40	237.6 ( 41.11 )	195.9 ( 32.45 )
Female, n=49,46	277.9 ( 29.40 )	259.1 ( 30.54 )
Male, n=252, 274	261.4 ( 12.95 )	253.5 ( 12.43 )
Race group, White, n=210,223	275.2 ( 14.21 )	260.0 ( 13.80 )
Race group, African Am/African H., n=31,29	228.5 ( 37.07 )	230.2 ( 38.23 )
Race group, Asian, n=29,38	212.1 ( 38.34 )	244.8 ( 33.53 )
Race group, Other, n=31,30	273.4 ( 36.97 )	247.3 ( 37.67 )

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

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-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-34.5

upper limit

38.2

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-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

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

-31.2

upper limit

111.5

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-3.9

Confidence interval

level

95%

sides

2-sided

lower limit

-122.3

upper limit

114.5

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

10.8

Confidence interval

level

95%

sides

2-sided

lower limit

-22.9

upper limit

44.5

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

7.3

Confidence interval

level

95%

sides

2-sided

lower limit

-35

upper limit

49.6

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-60.7

upper limit

55.7

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

41.6

Confidence interval

level

95%

sides

2-sided

lower limit

-61.2

upper limit

144.5

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

15.2

Confidence interval

level

95%

sides

2-sided

lower limit

-23.6

upper limit

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

7.8

Confidence interval

level

95%

sides

2-sided

lower limit

-27.4

upper limit

43.1

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

18.8

Confidence interval

level

95%

sides

2-sided

lower limit

-64.2

upper limit

101.8

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-106.3

upper limit

103

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (net)

Point estimate

-32.6

Confidence interval

level

95%

sides

2-sided

lower limit

-132.2

upper limit

66.9

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 v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

26.1

Confidence interval

level

95%

sides

2-sided

lower limit

-77.3

upper limit

129.5

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 & as HIV infection progresses,the number of these cells declines.Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is latest pre-dose assessment (Day 1). Change from Baseline was post-dose visit value minus Baseline value. Adjusted mean & 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 estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, treatment & relevant subgroup interaction.For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as 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	356 ^[122]	358 ^[123]
Units: Cells per cubic millimeter
arithmetic mean (standard error)
Baseline plasma HIV-1 RNA,<=100000, n=214,223	295.7 ( 14.14 )	296.1 ( 13.84 )
Baseline plasma HIV-1 RNA,>100000, n=56, 64	334.3 ( 27.77 )	329.6 ( 26.15 )
Baseline CD4+ cell count,<=200, n=17, 24	290.2 ( 50.44 )	272.9 ( 42.29 )
Baseline CD4+ cell count,>200, n=253, 263	304.7 ( 12.97 )	306.2 ( 12.71 )
Age group, <35,n=155, 167	298.0 ( 16.59 )	316.0 ( 15.93 )
Age group-1, 35 to <50, n=92, 87	305.6 ( 21.48 )	302.1 ( 22.11 )
Age group-1, >=50, n=23,33	337.4 ( 43.01 )	242.2 ( 35.83 )
Female, n=43, 43	346.6 ( 31.40 )	321.7 ( 31.67 )
Male, n=227, 244	295.9 ( 13.66 )	300.0 ( 13.20 )
Race group, White, n=190,201	314.2 ( 14.93 )	314.0 ( 14.53 )
Race group, African Am/African H., n=26, 26	243.8 ( 40.42 )	295.1 ( 40.39 )
Race group, Asian, n=26, 34	244.0 ( 40.47 )	264.1 ( 35.41 )
Race group, Other, n=28,26	346.2 ( 38.87 )	279.9 ( 40.42 )

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

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

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

4.7

Confidence interval

level

95%

sides

2-sided

lower limit

-69.4

upper limit

78.8

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

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-39.2

upper limit

38.3

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

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-18

Confidence interval

level

95%

sides

2-sided

lower limit

-63.2

upper limit

27.1

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

Number of subjects included in analysis

714

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

-57

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

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

66.2

Confidence interval

level

95%

sides

2-sided

lower limit

-43.7

upper limit

176.2

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

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

24.9

Confidence interval

level

95%

sides

2-sided

lower limit

-62.5

upper limit

112.3

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

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-41.5

upper limit

33.1

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

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-40.6

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

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-51.3

Confidence interval

level

95%

sides

2-sided

lower limit

-163.6

upper limit

60.9

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

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (net)

Point estimate

-20.1

Confidence interval

level

95%

sides

2-sided

lower limit

-125.3

upper limit

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

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

-1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-37.2

upper limit

34.1

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

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

17.4

Confidence interval

level

95%

sides

2-sided

lower limit

-111.1

upper limit

145.8

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

714

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (net)

Point estimate

95.2

Confidence interval

level

95%

sides

2-sided

lower limit

-14.8

upper limit

205.2

Secondary: Change from Baseline in 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 EuroQol – 5 Dimensions – 5 Levels (EQ-5D-5L) utility score at Weeks 4, 24, 48

End point description

EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The 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 and 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. Baseline was the latest pre-dose assessment (Day 1) and change from Baseline=post-dose value minus Baseline value. Only those participants available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

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

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[124]	358 ^[125]
Units: Scores on a scale
arithmetic mean (standard error)
Week 4, n=349, 348	0.0130 ( 0.00362 )	0.0078 ( 0.00353 )
Week 24, n=352, 351	0.0131 ( 0.00371 )	0.0168 ( 0.00333 )
Week 48, n=352, 351	0.0134 ( 0.00384 )	0.0129 ( 0.00349 )

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

Statistical Analysis 1

Statistical analysis description

Week 4. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit with visit as the repeated factor..

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.302

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.0052

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0047

upper limit

0.0152

Statistical Analysis 3

Statistical analysis description

Week48. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit with visit as the repeated factor..

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

P-value

= 0.934

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.0004

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0098

upper limit

0.0106

Statistical Analysis 2

Statistical analysis description

Week24. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit with visit as the repeated factor.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.45

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.0038

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0136

upper limit

0.006

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

End point type

Secondary

End point timeframe

Baseline (Day 1) and Week 96

End point values	DTG + 3TC-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	352 ^[126]	351 ^[127]
Units: Scores on a scale
arithmetic mean (standard error)	0.0079 ( 0.00450 )	0.0091 ( 0.00408 )

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

Statistical 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-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

703

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.842

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

-0.0012

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0132

upper limit

0.0107

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

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	352 ^[128]	351 ^[129]
Units: Scores on a scale
arithmetic mean (standard error)	0.0143 ( 0.00388 )	0.0135 ( 0.00365 )

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

Statistical 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

703

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.879

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.0008

Confidence interval

level

95%

sides

2-sided

lower limit

-0.0097

upper limit

0.0113

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 provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). MMRM was run on the LOCF dataset, using the observed margins (OM) option. Baseline was the latest pre-dose assessment value (Day 1) 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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	356 ^[130]	358 ^[131]
Units: Scores on a scale
arithmetic mean (standard error)
Week 4, n=349, 348	2.3 ( 0.48 )	1.2 ( 0.52 )
Week 24, n=352, 350	3.7 ( 0.54 )	3.2 ( 0.51 )
Week 48, n=352, 350	4.3 ( 0.49 )	2.8 ( 0.49 )

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

Statistical Analysis 1

Statistical analysis description

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

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.137

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

2.4

Statistical Analysis 3

Statistical analysis description

Week48. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA (factor),Baseline CD4+ cell count (factor), Baseline EQ-5D thermometer, treatment*visit and Baseline EQ-5D thermometer*visit with visit as the repeated factor.

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.031

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

2.8

Statistical Analysis 2

Statistical analysis description

Week24. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA (factor),Baseline CD4+ cell count (factor), Baseline EQ-5D thermometer, treatment*visit and Baseline EQ-5D thermometer*visit with visit as the repeated factor

Comparison groups

DTG + 3TC-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

714

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.458

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

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 (Day 1) 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-Double blind phase	DTG + TDF/FTC-Double blind phase
Number of subjects analysed	352 ^[132]	350 ^[133]
Units: Scores on a scale
arithmetic mean (standard error)	4.1 ( 0.51 )	2.4 ( 0.56 )

Notes
[132] - ITT-E Population.
[133] - ITT-E Population.

Statistical Analysis 1

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-Double blind phase v DTG + TDF/FTC-Double blind phase

Number of subjects included in analysis

702

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.027

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

3.2

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

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	352 ^[134]	350 ^[135]
Units: Scores on a scale
arithmetic mean (standard error)	5.2 ( 0.48 )	3.0 ( 0.50 )

Notes
[134] - ITT-E Population.
[135] - ITT-E Population.

Statistical 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

702

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.001

Method

MMRM

Parameter type

Mean difference (net)

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

3.6

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 + Open-label Phase. Safety-Continuation Population was used for the Continuation Phase which comprises 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 + 3TC-Continuation Phase

Reporting group description

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

Reporting group title

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

Reporting group description

Serious adverse events	DTG + 3TC-Double-blind Phase + Open-label Phase	DTG + 3TC-Continuation Phase	DTG + TDF/FTC-Double-blind Phase + Open-label Phase
Total subjects affected by serious adverse events
subjects affected / exposed	37 / 356 (10.39%)	5 / 233 (2.15%)	38 / 358 (10.61%)
number of deaths (all causes)	1	0	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anogenital warts
subjects affected / exposed	2 / 356 (0.56%)	0 / 233 (0.00%)	0 / 358 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Clear cell renal cell carcinoma
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hodgkin's disease
subjects affected / exposed	2 / 356 (0.56%)	0 / 233 (0.00%)	0 / 358 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Varicose vein
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	2 / 358 (0.56%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chest pain
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 1	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 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary sarcoidosis
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Psychiatric disorders
Major depression
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Suicide attempt
subjects affected / exposed	3 / 356 (0.84%)	0 / 233 (0.00%)	0 / 358 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Substance-induced psychotic disorder
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychotic disorder
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Delirium
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Suicidal ideation
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Bipolar I disorder
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Head injury
subjects affected / exposed	1 / 356 (0.28%)	1 / 233 (0.43%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Joint dislocation
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Post lumbar puncture syndrome
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Tendon rupture
subjects affected / exposed	0 / 356 (0.00%)	1 / 233 (0.43%)	0 / 358 (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
Jaw fracture
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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 injuries
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Coronary artery stenosis
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Coronary artery disease
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Polyneuropathy
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Acute polyneuropathy
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastric ulcer haemorrhage
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Intestinal obstruction
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anal fistula
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatitis toxic
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Nephrolithiasis
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	3 / 358 (0.84%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arthritis reactive
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess limb
subjects affected / exposed	2 / 356 (0.56%)	0 / 233 (0.00%)	0 / 358 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	2 / 356 (0.56%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatitis A
subjects affected / exposed	3 / 356 (0.84%)	1 / 233 (0.43%)	4 / 358 (1.12%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	1 / 356 (0.28%)	2 / 233 (0.86%)	4 / 358 (1.12%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Anal abscess
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Acute hepatitis C
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Cellulitis
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	2 / 358 (0.56%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chagoma
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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 respiratory tract infection
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Helicobacter gastritis
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Herpes zoster
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
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	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Perineal abscess
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Encephalitis
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Appendicitis perforated
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	1 / 356 (0.28%)	0 / 233 (0.00%)	0 / 358 (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
Erysipelas
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 356 (0.00%)	0 / 233 (0.00%)	1 / 358 (0.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
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 + 3TC-Continuation Phase	DTG + TDF/FTC-Double-blind Phase + Open-label Phase
Total subjects affected by non serious adverse events
subjects affected / exposed	272 / 356 (76.40%)	46 / 233 (19.74%)	268 / 358 (74.86%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts
subjects affected / exposed	14 / 356 (3.93%)	0 / 233 (0.00%)	17 / 358 (4.75%)
occurrences all number	14	0	19
Vascular disorders
Hypertension
subjects affected / exposed	16 / 356 (4.49%)	5 / 233 (2.15%)	14 / 358 (3.91%)
occurrences all number	18	9	14
Nervous system disorders
Headache
subjects affected / exposed	51 / 356 (14.33%)	7 / 233 (3.00%)	47 / 358 (13.13%)
occurrences all number	80	8	82
Dizziness
subjects affected / exposed	10 / 356 (2.81%)	0 / 233 (0.00%)	10 / 358 (2.79%)
occurrences all number	13	0	10
Paraesthesia
subjects affected / exposed	4 / 356 (1.12%)	0 / 233 (0.00%)	9 / 358 (2.51%)
occurrences all number	4	0	10
General disorders and administration site conditions
Fatigue
subjects affected / exposed	16 / 356 (4.49%)	0 / 233 (0.00%)	14 / 358 (3.91%)
occurrences all number	19	0	15
Pyrexia
subjects affected / exposed	18 / 356 (5.06%)	0 / 233 (0.00%)	12 / 358 (3.35%)
occurrences all number	24	0	13
Influenza like illness
subjects affected / exposed	19 / 356 (5.34%)	0 / 233 (0.00%)	16 / 358 (4.47%)
occurrences all number	20	0	25
Immune system disorders
Seasonal allergy
subjects affected / exposed	8 / 356 (2.25%)	0 / 233 (0.00%)	8 / 358 (2.23%)
occurrences all number	10	0	12
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	50 / 356 (14.04%)	0 / 233 (0.00%)	53 / 358 (14.80%)
occurrences all number	69	0	73
Nausea
subjects affected / exposed	13 / 356 (3.65%)	0 / 233 (0.00%)	32 / 358 (8.94%)
occurrences all number	13	0	37
Dyspepsia
subjects affected / exposed	13 / 356 (3.65%)	0 / 233 (0.00%)	12 / 358 (3.35%)
occurrences all number	20	0	13
Haemorrhoids
subjects affected / exposed	21 / 356 (5.90%)	0 / 233 (0.00%)	16 / 358 (4.47%)
occurrences all number	25	0	17
Abdominal pain
subjects affected / exposed	16 / 356 (4.49%)	0 / 233 (0.00%)	16 / 358 (4.47%)
occurrences all number	16	0	19
Abdominal pain upper
subjects affected / exposed	6 / 356 (1.69%)	0 / 233 (0.00%)	10 / 358 (2.79%)
occurrences all number	9	0	12
Vomiting
subjects affected / exposed	11 / 356 (3.09%)	0 / 233 (0.00%)	9 / 358 (2.51%)
occurrences all number	12	0	10
Gastritis
subjects affected / exposed	10 / 356 (2.81%)	0 / 233 (0.00%)	6 / 358 (1.68%)
occurrences all number	11	0	6
Toothache
subjects affected / exposed	11 / 356 (3.09%)	0 / 233 (0.00%)	9 / 358 (2.51%)
occurrences all number	15	0	11
Gastrooesophageal reflux disease
subjects affected / exposed	10 / 356 (2.81%)	0 / 233 (0.00%)	7 / 358 (1.96%)
occurrences all number	10	0	7
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	12 / 356 (3.37%)	0 / 233 (0.00%)	15 / 358 (4.19%)
occurrences all number	13	0	15
Cough
subjects affected / exposed	13 / 356 (3.65%)	0 / 233 (0.00%)	19 / 358 (5.31%)
occurrences all number	13	0	19
Rhinitis allergic
subjects affected / exposed	15 / 356 (4.21%)	0 / 233 (0.00%)	5 / 358 (1.40%)
occurrences all number	24	0	5
Respiratory disorder
subjects affected / exposed	8 / 356 (2.25%)	0 / 233 (0.00%)	5 / 358 (1.40%)
occurrences all number	11	0	7
Nasal congestion
subjects affected / exposed	3 / 356 (0.84%)	0 / 233 (0.00%)	8 / 358 (2.23%)
occurrences all number	3	0	8
Asthma
subjects affected / exposed	8 / 356 (2.25%)	0 / 233 (0.00%)	3 / 358 (0.84%)
occurrences all number	8	0	3
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	9 / 356 (2.53%)	0 / 233 (0.00%)	7 / 358 (1.96%)
occurrences all number	9	0	8
Rash
subjects affected / exposed	11 / 356 (3.09%)	0 / 233 (0.00%)	8 / 358 (2.23%)
occurrences all number	11	0	13
Psychiatric disorders
Insomnia
subjects affected / exposed	29 / 356 (8.15%)	0 / 233 (0.00%)	36 / 358 (10.06%)
occurrences all number	33	0	40
Anxiety
subjects affected / exposed	19 / 356 (5.34%)	0 / 233 (0.00%)	15 / 358 (4.19%)
occurrences all number	24	0	18
Depression
subjects affected / exposed	18 / 356 (5.06%)	0 / 233 (0.00%)	17 / 358 (4.75%)
occurrences all number	20	0	18
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	22 / 356 (6.18%)	0 / 233 (0.00%)	25 / 358 (6.98%)
occurrences all number	31	0	28
Arthralgia
subjects affected / exposed	7 / 356 (1.97%)	0 / 233 (0.00%)	22 / 358 (6.15%)
occurrences all number	8	0	24
Myalgia
subjects affected / exposed	5 / 356 (1.40%)	0 / 233 (0.00%)	9 / 358 (2.51%)
occurrences all number	6	0	9
Pain in extremity
subjects affected / exposed	8 / 356 (2.25%)	0 / 233 (0.00%)	6 / 358 (1.68%)
occurrences all number	10	0	6
Musculoskeletal pain
subjects affected / exposed	4 / 356 (1.12%)	0 / 233 (0.00%)	10 / 358 (2.79%)
occurrences all number	4	0	11
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	37 / 356 (10.39%)	7 / 233 (3.00%)	33 / 358 (9.22%)
occurrences all number	50	8	41
Nasopharyngitis
subjects affected / exposed	49 / 356 (13.76%)	7 / 233 (3.00%)	58 / 358 (16.20%)
occurrences all number	74	8	84
Influenza
subjects affected / exposed	24 / 356 (6.74%)	0 / 233 (0.00%)	18 / 358 (5.03%)
occurrences all number	28	0	20
Bronchitis
subjects affected / exposed	30 / 356 (8.43%)	0 / 233 (0.00%)	21 / 358 (5.87%)
occurrences all number	36	0	23
Syphilis
subjects affected / exposed	38 / 356 (10.67%)	6 / 233 (2.58%)	40 / 358 (11.17%)
occurrences all number	45	6	47
Pharyngitis
subjects affected / exposed	38 / 356 (10.67%)	6 / 233 (2.58%)	30 / 358 (8.38%)
occurrences all number	49	8	43
Herpes zoster
subjects affected / exposed	8 / 356 (2.25%)	0 / 233 (0.00%)	13 / 358 (3.63%)
occurrences all number	8	0	13
Tonsillitis
subjects affected / exposed	13 / 356 (3.65%)	0 / 233 (0.00%)	12 / 358 (3.35%)
occurrences all number	15	0	13
Gonorrhoea
subjects affected / exposed	16 / 356 (4.49%)	0 / 233 (0.00%)	13 / 358 (3.63%)
occurrences all number	22	0	18
Gastroenteritis
subjects affected / exposed	17 / 356 (4.78%)	0 / 233 (0.00%)	15 / 358 (4.19%)
occurrences all number	19	0	15
Sinusitis
subjects affected / exposed	15 / 356 (4.21%)	0 / 233 (0.00%)	15 / 358 (4.19%)
occurrences all number	17	0	20
Pharyngotonsillitis
subjects affected / exposed	15 / 356 (4.21%)	0 / 233 (0.00%)	12 / 358 (3.35%)
occurrences all number	26	0	18
Respiratory tract infection viral
subjects affected / exposed	8 / 356 (2.25%)	0 / 233 (0.00%)	9 / 358 (2.51%)
occurrences all number	10	0	15
Respiratory tract infection
subjects affected / exposed	9 / 356 (2.53%)	0 / 233 (0.00%)	10 / 358 (2.79%)
occurrences all number	13	0	19
Suspected COVID-19
subjects affected / exposed	0 / 356 (0.00%)	8 / 233 (3.43%)	0 / 358 (0.00%)
occurrences all number	0	8	0
COVID-19
subjects affected / exposed	0 / 356 (0.00%)	16 / 233 (6.87%)	0 / 358 (0.00%)
occurrences all number	0	18	0
Conjunctivitis
subjects affected / exposed	8 / 356 (2.25%)	0 / 233 (0.00%)	6 / 358 (1.68%)
occurrences all number	8	0	6
Anal chlamydia infection
subjects affected / exposed	9 / 356 (2.53%)	0 / 233 (0.00%)	5 / 358 (1.40%)
occurrences all number	16	0	5
Proctitis gonococcal
subjects affected / exposed	8 / 356 (2.25%)	0 / 233 (0.00%)	9 / 358 (2.51%)
occurrences all number	12	0	12
Oral herpes
subjects affected / exposed	9 / 356 (2.53%)	0 / 233 (0.00%)	8 / 358 (2.23%)
occurrences all number	11	0	9
Acute sinusitis
subjects affected / exposed	4 / 356 (1.12%)	0 / 233 (0.00%)	8 / 358 (2.23%)
occurrences all number	4	0	9
Tooth infection
subjects affected / exposed	10 / 356 (2.81%)	0 / 233 (0.00%)	7 / 358 (1.96%)
occurrences all number	10	0	7
Oropharyngeal gonococcal infection
subjects affected / exposed	8 / 356 (2.25%)	0 / 233 (0.00%)	7 / 358 (1.96%)
occurrences all number	9	0	8
Chlamydial infection
subjects affected / exposed	14 / 356 (3.93%)	0 / 233 (0.00%)	10 / 358 (2.79%)
occurrences all number	15	0	10
Urethritis
subjects affected / exposed	9 / 356 (2.53%)	0 / 233 (0.00%)	13 / 358 (3.63%)
occurrences all number	11	0	13
Urinary tract infection
subjects affected / exposed	9 / 356 (2.53%)	0 / 233 (0.00%)	13 / 358 (3.63%)
occurrences all number	11	0	13
Metabolism and nutrition disorders
Vitamin D deficiency
subjects affected / exposed	25 / 356 (7.02%)	0 / 233 (0.00%)	22 / 358 (6.15%)
occurrences all number	25	0	23

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

01 Dec 2017

Amendment No. 1: The double barrier method of contraception (male condom combined with a vaginal spermicide) was added in this study 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 the Portuguese National Ethics Committee for Clinical Research. Assessment of weight at Weeks 96 and 144 was added to monitor the incidence of significant weight gain with dolutegravir use. Assessment of inflammation biomarkers (IL-6, hs-CRP) at Day 1, and Weeks 48, 96 and 144, was added as a new exploratory endpoint. Assessment of telomere length at Day 1, and Weeks 96 and 144, was added as a new exploratory endpoint. For clarification purposes, the ‘peripheral blood mononuclear cell (PBMC)’ sample in Time and Events table and 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 dolutegravir tablets was added to Investigational Product and Other Study Treatment to allow use of commercial material as well as clinical trial material during the study. The physical description for open-label lamivudine was corrected. Standard procedures for forwarding pregnancy information to the Antiretroviral Pregnancy Register were added. For clarification purposes, the AE severity gradings in were updated to be consistent. This change has no impact on the investigator’s evaluation of adverse events. Minor revisions were made to the text to provide updated information, correct errors and improve accuracy and consistency.

14 Jun 2018

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 IB 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 (FRP) (Section 12.9.1) was updated to exclude the double barrier method of contraception, which does not meet updated GSK/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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

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 144

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

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

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

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 144

Secondary: Number of Participants With AEs by Maximum Severity Grades up to Week 144

Secondary: Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade up to Week 144

Secondary: Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade 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 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 Week 144

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

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 96

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