An Efficacy, Safety, and Tolerability Study Comparing Dolutegravir (DTG) Plus Lamivudine (3TC) With Dolutegravir Plus Tenofovir/Emtricitabine in Treatment naïve HIV Infected Subjects (Gemini 2)

• ClinicalTrials.gov Identifier: NCT02831764
• Recruitment Status: Active, not recruiting
• First Posted: July 13, 2016
• Results First Posted: April 22, 2019
• Last Update Posted: December 17, 2020
• Sponsor: ViiV Healthcare
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): ViiV Healthcare

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Conditions: Infection, Human Immunodeficiency Virus; HIV Infections
• Interventions: Drug: Dolutegravir (DTG); Drug: Lamivudine (3TC); Drug: Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC FDC)
• Enrollment: 722

Participant Flow

Recruitment Details	This study is a Phase 3, randomized, double-blind, parallel group, non-inferiority study. A total of 104 investigational centers in 18 countries randomized one or more participants in this multicenter study. The results presented are based on the primary analysis at Week 48.
Pre-assignment Details	Total of 722 participants were enrolled and randomized; however only 719 participants (3 participants were never dosed following randomization as they withdrew consent to participate in study) were dosed in to the study to receive either dolutegravir plus lamivudine (DTG+3TC) or dolutegravir plus tenofovir/emtricitabine (DTG+TDF/FTC).

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC fixed dose combination (FDC) administered orally, once daily for 48 weeks.
Period Title: Overall Study
Started	360	359
Completed	0	0
Not Completed	360	359
Reason Not Completed
Protocol specific withdrawal criteria	0	2
Withdrawal by Subject	7	6
Physician Decision	2	2
Lost to Follow-up	6	5
Adverse Event	8	5
Lack of Efficacy	2	2
Protocol Violation	5	2
Ongoing at the time of the analysis	330	335

Baseline Characteristics

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC	Total
Arm/Group Description		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		360	359	719
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	360 participants	359 participants	719 participants
		34.6 (10.72)	34.4 (10.35)	34.5 (10.53)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	360 participants	359 participants	719 participants
	Female	54 15.0%	46 12.8%	100 13.9%
	Male	306 85.0%	313 87.2%	619 86.1%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	360 participants	359 participants	719 participants
American (Am) Indian or Alaska (Al.) native		21 5.8%	24 6.7%	45 6.3%
Asian-Central/South Asian heritage (H.)		0 0.0%	3 0.8%	3 0.4%
Asian - East Asian H.		28 7.8%	26 7.2%	54 7.5%
Asian - South East Asian H.		6 1.7%	1 0.3%	7 1.0%
Black or African Am		55 15.3%	40 11.1%	95 13.2%
Native Hawaiian or other Pacific Islander		0 0.0%	5 1.4%	5 0.7%
White (Wt)-Arabic/North African H.		3 0.8%	3 0.8%	6 0.8%
Wt-Wt/Caucasian (Ca.)/European (Eu.) H.		234 65.0%	246 68.5%	480 66.8%
Am Indian or Al. native and Wt		12 3.3%	10 2.8%	22 3.1%
Black or African Am and Wt		1 0.3%	1 0.3%	2 0.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL (c/mL) at Week 48
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.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT-E Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed	360	359
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	93; (90.4 to 95.7)	94; (91.4 to 96.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Treatment with DTG+ 3TC was to be declared non-inferior to treatment with DTG+TDF/FTC if the lower end of a two-sided 95% confidence interval for the difference between the two groups in response rates at Week 48 was greater than -10%.
Method of Estimation	Estimation Parameter	Adjusted difference in proportion
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -4.3 to 2.9
	Estimation Comments	Difference in proportion was based on CMH stratified analysis adjusting for Baseline stratification factors: Plasma HIV-1 RNA (<= vs. >100,000 copies per milliliter) and CD4+ cell count (<= vs. >200 cells per cubic millimeter [cells/mm^3]).

2. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Weeks 24
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.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT-E Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed	360	359
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	94; (91.4 to 96.4)	94; (91.4 to 96.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Treatment with DTG+ 3TC was to be declared non-inferior to treatment with DTG+TDF/FTC if the lower end of a two-sided 95% confidence interval for the difference between the two groups in response rates at Week 48 was greater than -10%.
Method of Estimation	Estimation Parameter	Adjusted difference in proportion
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -3.4 to 3.6
	Estimation Comments	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).

3. Secondary Outcome

Title	Time to Viral Suppression (HIV-1 RNA <50 c/mL)
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. Median along with first Quartile and third Quartile have been presented.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

ITT-E Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed	360	359
Median (Inter-Quartile Range); Unit of Measure: Days
	29.0; (29.0 to 55.0)	29.0; (29.0 to 57.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.825
	Comments	The generalised Wilcoxon procedure was used to estimate a p-value for detecting a difference in cumulative incidence curves between treatment groups.
	Method	Generalised Wilcoxon procedure
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.18
	Estimation Comments	Hazard ratios were estimated using the Cox proportional hazard regression model.

4. Secondary Outcome

Title	CD4+ Cell Counts at Weeks 24 and 48
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.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Mean (Standard Deviation); Unit of Measure: Cells/mm^3
Week 24, n=349,345	Number Analyzed	349 participants	345 participants
		650.4 (257.02)	633.0 (287.37)
Week 48, n=337,340	Number Analyzed	337 participants	340 participants
		688.1 (266.39)	689.8 (308.49)

5. Secondary Outcome

Title	Changes From Baseline in CD4+ Cell Counts at Week 24 and 48
Description	CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+ cells. Analysis was performed by flow cytometry. Baseline value is defined as the the latest pre-dose assessment. Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted least mean and standard error has been presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for the following covariates/factors: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction, and Baseline CD4+ cell count and visit interaction, with visit as the repeated factor.
Time Frame	Baseline and Weeks 24, 48

Outcome Measure Data

Analysis Population Description

ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Least Squares Mean (Standard Error); Unit of Measure: Cells/mm^3
Week 24, n=349, 345	Number Analyzed	349 participants	345 participants
		188.8 (8.77)	163.2 (9.08)
Week 48, n=337, 340	Number Analyzed	337 participants	340 participants
		225.7 (8.94)	217.2 (9.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.043
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	25.6
	Confidence Interval	(2-Sided) 95%; 0.8 to 50.4
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.523
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	8.5
	Confidence Interval	(2-Sided) 95%; -17.7 to 34.8
	Estimation Comments	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.

6. Secondary Outcome

Title	Number of Participants With HIV-1 Disease Progression
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.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

ITT-E Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed	360	359
Measure Type: Count of Participants; Unit of Measure: Participants
No disease progression	356 98.9%	358 99.7%
From CDC Stage 1 to CDC Stage 3 Event	0 0.0%	0 0.0%
From CDC Stage 2 to CDC Stage 3 Event	1 0.3%	1 0.3%
From CDC Stage 3 to New CDC Stage 3 Event	1 0.3%	0 0.0%
From CDC Stage 1, 2 or 3 to Death	2 0.6%	0 0.0%

7. Secondary Outcome

Title	Number of Participants With Treatment-emergent Genotypic Resistance
Description	Number of participants, who meet 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.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Viral Genotypic Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed	2	2
Measure Type: Count of Participants; Unit of Measure: Participants
INSTI Mutations	0 0.0%	0 0.0%
Major mutations of the NRTI	0 0.0%	0 0.0%

8. Secondary Outcome

Title	Number of Participants With Treatment-emergent Phenotypic Resistance
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 were interpreted through a proprietary algorithm (from Monogram Biosciences) and provides the overall susceptibility of the drugs (Abacavir [ABC], elvitegravir [EGV], raltegravir [RAL], zidovudine [AZT], stavudine [D4T], didanosine [DDI]), emtricitabine [FTC], tenofovir disiproxil fumarate [TDF]). Partially sensitive and resistant cells were considered resistant in this analysis. Number of participants with phenotype at time of CVW by phenotypic cut-off at or prior to Week 48 have been presented. The Viral Phenotypic Population comprised of all participants in the ITT-E population who have available on-treatment phenotypic resistance data. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Viral Phenotypic Population

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		2	2
Measure Type: Count of Participants; Unit of Measure: Participants
INSTI, DTG, Sensitive, n=2,1	Number Analyzed	2 participants	1 participants
		2 100.0%	1 100.0%
INSTI, DTG, Resistant, n=2,1	Number Analyzed	2 participants	1 participants
		0 0.0%	0 0.0%
INSTI, EGV, Sensitive, n=2,1	Number Analyzed	2 participants	1 participants
		2 100.0%	1 100.0%
INSTI, EGV, Resistant, n=2,1	Number Analyzed	2 participants	1 participants
		0 0.0%	0 0.0%
INSTI, RAL, Sensitive, n=2,1	Number Analyzed	2 participants	1 participants
		2 100.0%	1 100.0%
INSTI, RAL, Resistant, n=2,1	Number Analyzed	2 participants	1 participants
		0 0.0%	0 0.0%
NRTI, 3TC, Sensitive, n=2,2	Number Analyzed	2 participants	2 participants
		2 100.0%	2 100.0%
NRTI, 3TC, Resistant, n=2,2	Number Analyzed	2 participants	2 participants
		0 0.0%	0 0.0%
NRTI, ABC, Sensitive, n=2,2	Number Analyzed	2 participants	2 participants
		2 100.0%	2 100.0%
NRTI, ABC, Resistant, n=2,2	Number Analyzed	2 participants	2 participants
		0 0.0%	0 0.0%
NRTI, AZT, Sensitive, n=2,2	Number Analyzed	2 participants	2 participants
		2 100.0%	2 100.0%
NRTI, AZT, Resistant, n=2,2	Number Analyzed	2 participants	2 participants
		0 0.0%	0 0.0%
NRTI, D4T, Sensitive, n=2,2	Number Analyzed	2 participants	2 participants
		2 100.0%	2 100.0%
NRTI, D4T, Resistant, n=2,2	Number Analyzed	2 participants	2 participants
		0 0.0%	0 0.0%
NRTI, DDI, Sensitive, n=2,2	Number Analyzed	2 participants	2 participants
		2 100.0%	2 100.0%
NRTI, DDI, Resistant, n=2,2	Number Analyzed	2 participants	2 participants
		0 0.0%	0 0.0%
NRTI, FTC, Sensitive, n=2,2	Number Analyzed	2 participants	2 participants
		2 100.0%	2 100.0%
NRTI, FTC, Resistant, n=2,2	Number Analyzed	2 participants	2 participants
		0 0.0%	0 0.0%
NRTI, TDF, Sensitive, n=2,2	Number Analyzed	2 participants	2 participants
		2 100.0%	2 100.0%
NRTI, TDF, Resistant, n=2,2	Number Analyzed	2 participants	2 participants
		0 0.0%	0 0.0%

9. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE) and Serious AE (SAE)
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 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. Analyses presented herein used a data cut-off date of 22 May 2018 (for Week 48 database freeze), i.e. may include data collected after a participant's Week 48 visit.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed	360	359
Measure Type: Count of Participants; Unit of Measure: Participants
Any AE	267 74.2%	284 79.1%
Any SAE	29 8.1%	33 9.2%

10. Secondary Outcome

Title	Number of Participants With AEs by Maximum Severity Grades
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 Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented. Analyses presented herein used a data cut-off date of 22 May 2018 (for Week 48 database freeze), i.e. may include data collected after a participant's Week 48 visit.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed	360	359
Measure Type: Count of Participants; Unit of Measure: Participants
Grade 1 AEs	79 21.9%	93 25.9%
Grade 2 AEs	161 44.7%	159 44.3%
Grade 3 AEs	19 5.3%	29 8.1%
Grade 4 AEs	6 1.7%	3 0.8%
Grade 5 AEs	2 0.6%	0 0.0%

11. Secondary Outcome

Title	Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade
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. Analyses presented herein used a data cut-off date of 22 May 2018 (for Week 48 database freeze), i.e. may include data collected after a participant's Week 48 visit.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed	360	359
Measure Type: Count of Participants; Unit of Measure: Participants
Any drug related AE	55 15.3%	75 20.9%
Drug related AEs with maximum toxicity Grade 1	34 9.4%	53 14.8%
Drug related AEs with maximum toxicity Grade 2	17 4.7%	17 4.7%
Drug related AEs with maximum toxicity Grade 3	3 0.8%	4 1.1%
Drug related AEs with maximum toxicity Grade 4	1 0.3%	1 0.3%
Drug related AEs with maximum toxicity Grade 5	0 0.0%	0 0.0%

12. Secondary Outcome

Title	Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities
Description	Blood samples were collected up to Week 48 for assessment of platelet count, neutrophils, hemoglobin, and Leukocytes. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Only those participants with maximum post-Baseline emergent hematology toxicities in any of the listed hematology parameters have been presented.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed	360	359
Measure Type: Count of Participants; Unit of Measure: Participants
Hemoglobin, Grades 1 to 4	8 2.2%	7 1.9%
Hemoglobin, Grades 2 to 4	5 1.4%	4 1.1%
Hemoglobin, Grades 3 to 4	2 0.6%	1 0.3%
Hemoglobin, Grade 1	3 0.8%	3 0.8%
Hemoglobin, Grade 2	3 0.8%	3 0.8%
Hemoglobin, Grade 3	1 0.3%	1 0.3%
Hemoglobin, Grade 4	1 0.3%	0 0.0%
Leukocytes, Grades 1 to 4	4 1.1%	3 0.8%
Leukocytes, Grades 2 to 4	1 0.3%	0 0.0%
Leukocytes, Grades 3 to 4	0 0.0%	0 0.0%
Leukocytes, Grade 1	3 0.8%	3 0.8%
Leukocytes, Grade 2	1 0.3%	0 0.0%
Leukocytes, Grade 3	0 0.0%	0 0.0%
Leukocytes, Grade 4	0 0.0%	0 0.0%
Neutrophils, Grades 1 to 4	14 3.9%	6 1.7%
Neutrophils, Grades 2 to 4	4 1.1%	2 0.6%
Neutrophils, Grades 3 to 4	1 0.3%	1 0.3%
Neutrophils, Grade 1	10 2.8%	4 1.1%
Neutrophils, Grade 2	3 0.8%	1 0.3%
Neutrophils, Grade 3	1 0.3%	1 0.3%
Neutrophils, Grade 4	0 0.0%	0 0.0%
Platelets, Grades 1 to 4	11 3.1%	9 2.5%
Platelets, Grades 2 to 4	5 1.4%	5 1.4%
Platelets, Grades 3 to 4	0 0.0%	0 0.0%
Platelets, Grade 1	6 1.7%	4 1.1%
Platelets, Grade 2	5 1.4%	5 1.4%
Platelets, Grade 3	0 0.0%	0 0.0%
Platelets, Grade 4	0 0.0%	0 0.0%

13. Secondary Outcome

Title	Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities
Description	Blood samples were collected up to Week 48 for assessment of Alanine Aminotransferase (ALT), Aspartate aminotransferase (AST), Albumin, Alkaline Phosphatase (ALP), Bilirubin, Carbon dioxide (CO2), Cholesterol, Creatine kinase (CPK), Creatinine, Direct Bilirubin, Glomerular filtration rate (GFR), Hypercalcemia, Hyperglycemia, Hyperkalemia, Hypernatremia, Hypocalcemia, Hypoglycemia, Hypokalemia and Hyponatremia, Low density lipid (LDL) Cholesterol, Lactate Dehydrogenase, Lipase and Phosphate. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Only those participants with maximum post-Baseline emergent chemistry toxicities in any of the chemistry parameters have been presented.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed	360	359
Measure Type: Count of Participants; Unit of Measure: Participants
ALT, Grades 1 to 4	43 11.9%	51 14.2%
ALT, Grades 2 to 4	17 4.7%	22 6.1%
ALT, Grades 3 to 4	9 2.5%	10 2.8%
ALT, Grade 1	26 7.2%	29 8.1%
ALT, Grade 2	8 2.2%	12 3.3%
ALT, Grade 3	4 1.1%	4 1.1%
ALT, Grade 4	5 1.4%	6 1.7%
Albumin, Grades 1 to 4	0 0.0%	1 0.3%
Albumin, Grades 2 to 4	0 0.0%	1 0.3%
Albumin, Grades 3 to 4	0 0.0%	1 0.3%
Albumin, Grade 1	0 0.0%	0 0.0%
Albumin, Grade 2	0 0.0%	0 0.0%
Albumin, Grade 3	0 0.0%	1 0.3%
Albumin, Grade 4	0 0.0%	0 0.0%
ALP, Grades 1 to 4	6 1.7%	14 3.9%
ALP, Grades 2 to 4	2 0.6%	3 0.8%
ALP, Grades 3 to 4	0 0.0%	1 0.3%
ALP, Grade 1	4 1.1%	11 3.1%
ALP, Grade 2	2 0.6%	2 0.6%
ALP, Grade 3	0 0.0%	1 0.3%
ALP, Grade 4	0 0.0%	0 0.0%
AST, Grades 1 to 4	42 11.7%	56 15.6%
AST, Grades 2 to 4	17 4.7%	23 6.4%
AST, Grades 3 to 4	7 1.9%	12 3.3%
AST, Grade 1	25 6.9%	33 9.2%
AST, Grade 2	10 2.8%	11 3.1%
AST, Grade 3	3 0.8%	9 2.5%
AST, Grade 4	4 1.1%	3 0.8%
Bilirubin, Grades 1 to 4	33 9.2%	38 10.6%
Bilirubin, Grades 2 to 4	8 2.2%	11 3.1%
Bilirubin, Grades 3 to 4	3 0.8%	3 0.8%
Bilirubin, Grade 1	25 6.9%	27 7.5%
Bilirubin, Grade 2	5 1.4%	8 2.2%
Bilirubin, Grade 3	0 0.0%	2 0.6%
Bilirubin, Grade 4	3 0.8%	1 0.3%
CO2, Grades 1 to 4	71 19.7%	87 24.2%
CO2, Grades 2 to 4	6 1.7%	2 0.6%
CO2, Grades 3 to 4	0 0.0%	0 0.0%
CO2, Grade 1	65 18.1%	85 23.7%
CO2, Grade 2	6 1.7%	2 0.6%
CO2, Grade 3	0 0.0%	0 0.0%
CO2, Grade 4	0 0.0%	0 0.0%
Cholesterol, Grades 1 to 4	70 19.4%	26 7.2%
Cholesterol, Grades 2 to 4	11 3.1%	5 1.4%
Cholesterol, Grades 3 to 4	0 0.0%	0 0.0%
Cholesterol, Grade 1	59 16.4%	21 5.8%
Cholesterol, Grade 2	11 3.1%	5 1.4%
Cholesterol, Grade 3	0 0.0%	0 0.0%
Cholesterol, Grade 4	0 0.0%	0 0.0%
CK, Grades 1 to 4	61 16.9%	48 13.4%
CK, Grades 2 to 4	34 9.4%	28 7.8%
CK, Grades 3 to 4	19 5.3%	17 4.7%
CK, Grade 1	27 7.5%	20 5.6%
CK, Grade 2	15 4.2%	11 3.1%
CK, Grade 3	9 2.5%	6 1.7%
CK, Grade 4	10 2.8%	11 3.1%
Creatinine, Grades 1 to 4	14 3.9%	19 5.3%
Creatinine, Grades 2 to 4	3 0.8%	2 0.6%
Creatinine, Grades 3 to 4	0 0.0%	1 0.3%
Creatinine, Grade 1	11 3.1%	17 4.7%
Creatinine, Grade 2	3 0.8%	1 0.3%
Creatinine, Grade 3	0 0.0%	1 0.3%
Creatinine, Grade 4	0 0.0%	0 0.0%
Direct Bilirubin, Grades 1 to 4	7 1.9%	7 1.9%
Direct Bilirubin, Grades 2 to 4	7 1.9%	7 1.9%
Direct Bilirubin, Grades 3 to 4	7 1.9%	7 1.9%
Direct Bilirubin, Grade 1	0 0.0%	0 0.0%
Direct Bilirubin, Grade 2	0 0.0%	0 0.0%
Direct Bilirubin, Grade 3	7 1.9%	7 1.9%
Direct Bilirubin, Grade 4	0 0.0%	0 0.0%
GFR, Grades 1 to 4	154 42.8%	190 52.9%
GFR, Grades 2 to 4	154 42.8%	190 52.9%
GFR, Grades 3 to 4	13 3.6%	18 5.0%
GFR, Grade 1	0 0.0%	0 0.0%
GFR, Grade 2	141 39.2%	172 47.9%
GFR, Grade 3	13 3.6%	17 4.7%
GFR, Grade 4	0 0.0%	1 0.3%
Hypercalcaemia, Grades 1 to 4	3 0.8%	5 1.4%
Hypercalcaemia, Grades 2 to 4	0 0.0%	1 0.3%
Hypercalcaemia, Grades 3 to 4	0 0.0%	1 0.3%
Hypercalcemia, Grade 1	3 0.8%	4 1.1%
Hypercalcaemia, Grade 2	0 0.0%	0 0.0%
Hypercalcaemia, Grade 3	0 0.0%	0 0.0%
Hypercalcaemia, Grade 4	0 0.0%	1 0.3%
Hyperglycaemia, Grades 1 to 4	74 20.6%	57 15.9%
Hyperglycaemia, Grades 2 to 4	30 8.3%	21 5.8%
Hyperglycaemia, Grades 3 to 4	2 0.6%	3 0.8%
Hyperglycaemia, Grade 1	44 12.2%	36 10.0%
Hyperglycaemia, Grade 2	28 7.8%	18 5.0%
Hyperglycaemia, Grade 3	2 0.6%	2 0.6%
Hyperglycaemia, Grade 4	0 0.0%	1 0.3%
Hyperkalemia, Grades 1 to 4	4 1.1%	4 1.1%
Hyperkalemia, Grades 2 to 4	1 0.3%	0 0.0%
Hyperkalemia, Grades 3 to 4	0 0.0%	0 0.0%
Hyperkalemia, Grade 1	3 0.8%	4 1.1%
Hyperkalemia, Grade 2	1 0.3%	0 0.0%
Hyperkalemia, Grade 3	0 0.0%	0 0.0%
Hyperkalemia, Grade 4	0 0.0%	0 0.0%
Hypernatremia, Grades 1 to 4	1 0.3%	5 1.4%
Hypernatremia, Grades 2 to 4	0 0.0%	0 0.0%
Hypernatremia, Grades 3 to 4	0 0.0%	0 0.0%
Hypernatremia, Grade 1	1 0.3%	5 1.4%
Hypernatremia, Grade 2	0 0.0%	0 0.0%
Hypernatremia, Grade 3	0 0.0%	0 0.0%
Hypernatremia, Grade 4	0 0.0%	0 0.0%
Hypocalcaemia, Grades 1 to 4	7 1.9%	10 2.8%
Hypocalcaemia, Grades 2 to 4	1 0.3%	5 1.4%
Hypocalcaemia, Grades 3 to 4	0 0.0%	1 0.3%
Hypocalcaemia, Grade 1	6 1.7%	5 1.4%
Hypocalcaemia, Grade 2	1 0.3%	4 1.1%
Hypocalcaemia, Grade 3	0 0.0%	1 0.3%
Hypocalcaemia, Grade 4	0 0.0%	0 0.0%
Hypoglycaemia, Grades 1 to 4	13 3.6%	13 3.6%
Hypoglycaemia, Grades 2 to 4	4 1.1%	4 1.1%
Hypoglycaemia, Grades 3 to 4	3 0.8%	1 0.3%
Hypoglycaemia, Grade 1	9 2.5%	9 2.5%
Hypoglycaemia, Grade 2	1 0.3%	3 0.8%
Hypoglycaemia, Grade 3	2 0.6%	0 0.0%
Hypoglycaemia, Grade 4	1 0.3%	1 0.3%
Hypokalemia, Grades 1 to 4	3 0.8%	0 0.0%
Hypokalemia, Grades 2 to 4	0 0.0%	0 0.0%
Hypokalemia, Grades 3 to 4	0 0.0%	0 0.0%
Hypokalemia, Grade 1	3 0.8%	0 0.0%
Hypokalemia, Grade 2	0 0.0%	0 0.0%
Hypokalemia, Grade 3	0 0.0%	0 0.0%
Hypokalemia, Grade 4	0 0.0%	0 0.0%
Hyponatremia, Grades 1 to 4	14 3.9%	18 5.0%
Hyponatremia, Grades 2 to 4	0 0.0%	2 0.6%
Hyponatremia, Grades 3 to 4	0 0.0%	0 0.0%
Hyponatremia, Grade 1	14 3.9%	16 4.5%
Hyponatremia, Grade 2	0 0.0%	2 0.6%
Hyponatremia, Grade 3	0 0.0%	0 0.0%
Hyponatremia, Grade 4	0 0.0%	0 0.0%
LDL Cholesterol, Grades 1 to 4	48 13.3%	22 6.1%
LDL Cholesterol, Grades 2 to 4	14 3.9%	5 1.4%
LDL Cholesterol, Grades 3 to 4	3 0.8%	0 0.0%
LDL Cholesterol, Grade 1	34 9.4%	17 4.7%
LDL Cholesterol, Grade 2	11 3.1%	5 1.4%
LDL Cholesterol, Grade 3	3 0.8%	0 0.0%
LDL Cholesterol, Grade 4	0 0.0%	0 0.0%
Lactate Dehydrogenase, Grades 1 to 4	3 0.8%	2 0.6%
Lactate Dehydrogenase, Grades 2 to 4	3 0.8%	0 0.0%
Lactate Dehydrogenase, Grades 3 to 4	0 0.0%	0 0.0%
Lactate Dehydrogenase, Grade 1	0 0.0%	2 0.6%
Lactate Dehydrogenase, Grade 2	3 0.8%	0 0.0%
Lactate Dehydrogenase, Grade 3	0 0.0%	0 0.0%
Lactate Dehydrogenase, Grade 4	0 0.0%	0 0.0%
Lipase, Grades 1 to 4	48 13.3%	60 16.7%
Lipase, Grades 2 to 4	21 5.8%	28 7.8%
Lipase, Grades 3 to 4	2 0.6%	10 2.8%
Lipase, Grade 1	27 7.5%	32 8.9%
Lipase, Grade 2	19 5.3%	18 5.0%
Lipase, Grade 3	0 0.0%	9 2.5%
Lipase, Grade 4	2 0.6%	1 0.3%
Phosphate, Grades 1 to 4	53 14.7%	51 14.2%
Phosphate, Grades 2 to 4	31 8.6%	33 9.2%
Phosphate, Grades 3 to 4	2 0.6%	4 1.1%
Phosphate, Grade 1	22 6.1%	18 5.0%
Phosphate, Grade 2	29 8.1%	29 8.1%
Phosphate, Grade 3	2 0.6%	4 1.1%
Phosphate, Grade 4	0 0.0%	0 0.0%
Triglycerides, Grades 1 to 4	58 16.1%	52 14.5%
Triglycerides, Grades 2 to 4	11 3.1%	7 1.9%
Triglycerides, Grades 3 to 4	3 0.8%	1 0.3%
Triglycerides, Grade 1	47 13.1%	45 12.5%
Triglycerides, Grade 2	8 2.2%	6 1.7%
Triglycerides, Grade 3	3 0.8%	1 0.3%
Triglycerides, Grade 4	0 0.0%	0 0.0%

14. Secondary Outcome

Title	Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48
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. Number of participants who discontinued treatment due to AEs have been reported. Analyses presented herein used a data cut-off date of 19 January 2018 and 22 May 2018, respectively, for the Week 24 database freeze and Week 48 database freeze), i.e. may include data collected after a participant's Week 24 or 48 visit, respectively.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed	360	359
Measure Type: Count of Participants; Unit of Measure: Participants
Up to Week 24	6 1.7%	4 1.1%
Up to Week 48	8 2.2%	8 2.2%

15. Secondary Outcome

Title	Change From Baseline in Renal Biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48
Description	Blood and/or urine samples were collected to perform evaluation of renal biomarkers which included Serum Cystatin C and Serum RBP. Baseline value is the latest pre-dose assessment. Change from Baseline was defined as value at indicated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor.
Time Frame	Baseline and at Weeks 24, 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Least Squares Mean (Standard Error); Unit of Measure: Milligrams per Liter (mg/L)
Serum Cystatin C, Week 24, n=345,345	Number Analyzed	345 participants	345 participants
		-0.04 (0.005)	0.00 (0.005)
Serum Cystatin C, Week 48, n=335,336	Number Analyzed	335 participants	336 participants
		-0.05 (0.005)	-0.04 (0.006)
Serum RBP, Week 24, n=345,343	Number Analyzed	345 participants	343 participants
		1.2 (0.42)	1.4 (0.48)
Serum RBP, Week 48, n=334, 334	Number Analyzed	334 participants	334 participants
		0.6 (0.45)	-0.1 (0.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.05 to -0.02
	Estimation Comments	Week 24. Serum Cystatin C.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.022
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.00
	Estimation Comments	Week 48. Serum Cystatin C.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.797
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.4 to 1.1
	Estimation Comments	Week 24. Serum RBP

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.258
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -0.5 to 1.9
	Estimation Comments	Week 48. Serum RBP

16. Secondary Outcome

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
Description	Blood samples were collected to perform evaluation of renal biomarkers which included Serum GFR from cystatin C adjusted using CKD-EPI (GFR-cystatin C adjusted) and Serum or Plasma GFR from creatinine adjusted using CKD-EPI. Baseline value is the latest pre-dose Assessment. Change from Baseline was defined as value at the indicated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor.
Time Frame	Baseline and at Weeks 24, 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Mean (Standard Error); Unit of Measure: Milliliter/minute/1.73 meter^2
GFR Cystatin C adjusted, Week 24, n=345,345	Number Analyzed	345 participants	345 participants
		3.8 (0.66)	0.2 (0.65)
GFR Cystatin C adjusted, Week 48, n=335,336	Number Analyzed	335 participants	336 participants
		5.4 (0.64)	3.6 (0.64)
GFR creatinine adjusted, Week 24, n=346,344	Number Analyzed	346 participants	344 participants
		-12.0 (0.64)	-15.4 (0.59)
GFR creatinine adjusted, Week 48, n=335, 337	Number Analyzed	335 participants	337 participants
		-12.1 (0.60)	-15.4 (0.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95%; 1.8 to 5.4
	Estimation Comments	Week 24. GFR Cystatin C adjusted.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.056
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95%; 0.0 to 3.5
	Estimation Comments	Week 48. GFR Cystatin C adjusted.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95%; 1.7 to 5.2
	Estimation Comments	Week 24. GFR creatinine adjusted.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.3
	Confidence Interval	(2-Sided) 95%; 1.6 to 5.0
	Estimation Comments	Week 48. GFR creatinine adjusted.

17. Secondary Outcome

Title	Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Weeks 24, 48
Description	Blood and samples were collected to perform evaluation of renal biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the the latest pre-dose assessment. Change from Baseline was calculated as value at the inidcated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Time Frame	Baseline and at Weeks 24, 48

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Mean (Standard Deviation); Unit of Measure: Micromoles per Liter (umol/L)
Serum or Plasma Creatinine, Week 24, n=346, 344	Number Analyzed	346 participants	344 participants
		10.51 (0.548)	13.53 (0.507)
Serum or Plasma Creatinine, Week 48, n=335, 337	Number Analyzed	335 participants	337 participants
		10.32 (0.519)	13.44 (0.540)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.02
	Confidence Interval	(2-Sided) 95%; -4.49 to -1.55
	Estimation Comments	Week 24. Serum Plasma Creatinine

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.12
	Confidence Interval	(2-Sided) 95%; -4.59 to -1.65
	Estimation Comments	Week 48. Serum Plasma creatinine

18. Secondary Outcome

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
Description	Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers: Urine and Serum B2M, Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine. Baseline value was the latest pre-dose assessment. Change from Baseline was performed on log-transformed data. Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Geometric mean ratio and 95% CI of geometric mean ratio have been presented. Biomarkers were Adjusted for treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, loge transformed Baseline biomarker value, treatment and visit interaction, and loge transformed Baseline biomarker value and visit interaction; with visit as the repeated factor.
Time Frame	Baseline and Weeks 24, 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Geometric Mean (95% Confidence Interval); Unit of Measure: Ratio
Serum B2M, Week 24, n=344,346	Number Analyzed	344 participants	346 participants
		0.809; (0.794 to 0.824)	0.882; (0.867 to 0.898)
Serum B2M, Week 48, n=335,336	Number Analyzed	335 participants	336 participants
		0.811; (0.796 to 0.827)	0.887; (0.871 to 0.904)
Urine B2M, Week 24, n=124,106	Number Analyzed	124 participants	106 participants
		0.844; (0.755 to 0.944)	1.129; (0.974 to 1.309)
Urine B2M, Week 48, n=109, 103	Number Analyzed	109 participants	103 participants
		0.917; (0.804 to 1.046)	1.323; (1.066 to 1.642)
Urine Albumin/Creatinine, Week 24, n=259, 251	Number Analyzed	259 participants	251 participants
		0.907; (0.844 to 0.976)	1.021; (0.940 to 1.109)
Urine Albumin/Creatinine , Week 48, n=249, 240	Number Analyzed	249 participants	240 participants
		0.911; (0.835 to 0.994)	0.971; (0.891 to 1.058)
Urine B2M/Urine Creatinine , Week 24, n=122, 104	Number Analyzed	122 participants	104 participants
		0.880; (0.779 to 0.993)	1.126; (0.988 to 1.282)
Urine B2M/Urine Creatinine , Week 48, n=108, 103	Number Analyzed	108 participants	103 participants
		0.969; (0.854 to 1.099)	1.307; (1.077 to 1.586)
Urine Phosphate, Week 24, n=343, 340	Number Analyzed	343 participants	340 participants
		1.041; (0.955 to 1.134)	1.063; (0.978 to 1.157)
Urine Phosphate, Week 48, n=335, 332	Number Analyzed	335 participants	332 participants
		1.121; (1.031 to 1.220)	1.056; (0.974 to 1.144)
Urine Protein/Creatinine, Week 24, n=263,279	Number Analyzed	263 participants	279 participants
		0.818; (0.779 to 0.859)	0.991; (0.941 to 1.043)
Urine Protein/Creatinine , Week 48, n=259, 261	Number Analyzed	259 participants	261 participants
		0.866; (0.818 to 0.917)	1.007; (0.954 to 1.062)
Urine RBP 4, Week 24, n=340, 338	Number Analyzed	340 participants	338 participants
		0.656; (0.591 to 0.729)	0.824; (0.738 to 0.921)
Urine RBP 4, Week 48, n=333, 331	Number Analyzed	333 participants	331 participants
		0.740; (0.666 to 0.822)	0.819; (0.730 to 0.919)
Urine RBP 4/Urine Creatinine, Week 24, n=338, 335	Number Analyzed	338 participants	335 participants
		0.670; (0.614 to 0.730)	0.811; (0.741 to 0.888)
Urine RBP 4/Urine Creatinine, Week 48, n=331, 328	Number Analyzed	331 participants	328 participants
		0.749; (0.689 to 0.814)	0.844; (0.774 to 0.920)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.917
	Confidence Interval	(2-Sided) 95%; 0.893 to 0.941
	Estimation Comments	Week 24. Serum B2M.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.914
	Confidence Interval	(2-Sided) 95%; 0.890 to 0.939
	Estimation Comments	Week 48. Serum B2M.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.002
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.748
	Confidence Interval	(2-Sided) 95%; 0.621 to 0.901
	Estimation Comments	Week 24. Urine B2M.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.005
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.693
	Confidence Interval	(2-Sided) 95%; 0.538 to 0.892
	Estimation Comments	Week 48. Urine B2M.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.036
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.889
	Confidence Interval	(2-Sided) 95%; 0.796 to 0.992
	Estimation Comments	Week 24. Urine Albumin/Creatinine.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.308
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.938
	Confidence Interval	(2-Sided) 95%; 0.830 to 1.061
	Estimation Comments	Week 48. Urine Albumin/Creatinine.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.007
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.781
	Confidence Interval	(2-Sided) 95%; 0.654 to 0.934
	Estimation Comments	Week 24. Urine B2M/Urine Creatinine.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.012
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.742
	Confidence Interval	(2-Sided) 95%; 0.588 to 0.935
	Estimation Comments	Week 48. Urine B2M/Urine Creatinine.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.728
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.979
	Confidence Interval	(2-Sided) 95%; 0.868 to 1.104
	Estimation Comments	Week 24. Urine Phosphate.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.311
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	1.062
	Confidence Interval	(2-Sided) 95%; 0.945 to 1.194
	Estimation Comments	Week 48. Urine Phosphate.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.826
	Confidence Interval	(2-Sided) 95%; 0.769 to 0.887
	Estimation Comments	Week 24. Urine Protein/Creatinine.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.860
	Confidence Interval	(2-Sided) 95%; 0.795 to 0.930
	Estimation Comments	Week 48. Urine Protein/Creatinine.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.003
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.796
	Confidence Interval	(2-Sided) 95%; 0.683 to 0.927
	Estimation Comments	Week 24. Urine RBP 4

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.200
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.903
	Confidence Interval	(2-Sided) 95%; 0.773 to 1.056
	Estimation Comments	Week 48. Urine RBP 4

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.003
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.826
	Confidence Interval	(2-Sided) 95%; 0.728 to 0.936
	Estimation Comments	Week 24. Urine RBP/Urine Creatinine

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.052
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.888
	Confidence Interval	(2-Sided) 95%; 0.787 to 1.001
	Estimation Comments	Week 48. Urine RBP/Urine Creatinine

19. Secondary Outcome

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
Description	Blood samples were collected to perform evaluation of bone biomarkers which included bone-ALP, Serum Osteocalcin, PINP and CTX-1. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as value at the indicated time point minus Baseline value.
Time Frame	Baseline (Day 1) and at Weeks 24, 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Mean (Standard Error); Unit of Measure: Micrograms per Liter (ug/L)
Bone-ALP, Week 24, n=345, 346	Number Analyzed	345 participants	346 participants
		0.72 (0.171)	3.38 (0.244)
Bone-ALP, Week 48, n=334, 337	Number Analyzed	334 participants	337 participants
		1.24 (0.198)	4.33 (0.268)
Serum Osteocalcin, Week 24, n=345, 346	Number Analyzed	345 participants	346 participants
		2.13 (0.321)	6.80 (0.368)
Serum Osteocalcin, Week 48, n=335, 336	Number Analyzed	335 participants	336 participants
		0.40 (0.326)	6.30 (0.384)
PINP, Week 24, n=344, 346	Number Analyzed	344 participants	346 participants
		1.7 (0.95)	15.2 (1.12)
PINP, Week 48, n=335, 337	Number Analyzed	335 participants	337 participants
		0.4 (0.79)	13.3 (1.06)
CTX-1, Week 24, n=342, 342	Number Analyzed	342 participants	342 participants
		0.1541 (0.01247)	0.2812 (0.01406)
CTX-1, Week 48, n=332, 333	Number Analyzed	332 participants	333 participants
		0.1345 (0.01496)	0.3388 (0.01983)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.66
	Confidence Interval	(2-Sided) 95%; -3.25 to -2.08
	Estimation Comments	Week 24, Bone ALP

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.09
	Confidence Interval	(2-Sided) 95%; -3.75 to -2.44
	Estimation Comments	Week 48, Bone ALP

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.67
	Confidence Interval	(2-Sided) 95%; -5.63 to -3.71
	Estimation Comments	Week 28, Serum Osteocalcin

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5.90
	Confidence Interval	(2-Sided) 95%; -6.89 to -4.91
	Estimation Comments	Week 48, Serum Osteocalcin

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-13.5
	Confidence Interval	(2-Sided) 95%; -16.4 to -10.6
	Estimation Comments	Week 24, Serum PINP

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-12.8
	Confidence Interval	(2-Sided) 95%; -15.4 to -10.2
	Estimation Comments	Week 48, Serum PINP

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1270
	Confidence Interval	(2-Sided) 95%; -0.1640 to -0.0900
	Estimation Comments	Week 24, CTX-1

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2043
	Confidence Interval	(2-Sided) 95%; -0.2532 to -0.1554
	Estimation Comments	Week 48, CTX-1

20. Secondary Outcome

Title	Change From Baseline in Bone Biomarker-Serum Vitamin D at Weeks 24, 48
Description	Blood samples were collected to perform evaluation of bone biomarker serum vitamin D. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as value at the indicated time point minus Baseline value.
Time Frame	Baseline and at Weeks 24, 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Least Squares Mean (Standard Error); Unit of Measure: Nanomoles per Liter (nmol/L)
Serum Vitamin D, Week 24, n=346, 344	Number Analyzed	346 participants	344 participants
		11.2 (1.08)	15.4 (1.33)
Serum Vitamin D, Week 48, n=336, 335	Number Analyzed	336 participants	335 participants
		0.3 (0.92)	0.4 (1.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.015
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.2
	Confidence Interval	(2-Sided) 95%; -7.5 to -0.8
	Estimation Comments	Week 24

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.960
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -2.8 to 2.6
	Estimation Comments	Week 48

21. Secondary Outcome

Title	Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma High Density Lipoprotein (HDL) Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48
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).
Time Frame	Baseline and at Weeks 24, 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Mean (Standard Deviation); Unit of Measure: Percentage change
Serum or Plasma Cholesterol, Week 24, n=298, 310	Number Analyzed	298 participants	310 participants
		5.0 (16.85)	-4.5 (15.44)
Serum or Plasma Cholesterol, Week 48, n=298, 307	Number Analyzed	298 participants	307 participants
		9.3 (17.10)	-3.3 (14.61)
HDL Cholesterol, Direct, Week 24, n=299, 310	Number Analyzed	299 participants	310 participants
		13.9 (25.17)	7.2 (32.22)
HDL Cholesterol, Direct, Week 48, n=299, 307	Number Analyzed	299 participants	307 participants
		15.3 (23.75)	4.0 (21.86)
LDL Cholesterol, Week 24, n=298, 309	Number Analyzed	298 participants	309 participants
		3.8 (25.85)	-7.8 (21.13)
LDL Cholesterol, Week 48, n=297, 307	Number Analyzed	297 participants	307 participants
		10.7 (27.54)	-4.1 (20.39)
Triglycerides,Week 24, n=299, 310	Number Analyzed	299 participants	310 participants
		7.0 (40.45)	0.5 (44.01)
Triglycerides, Week 48, n=299, 307	Number Analyzed	299 participants	307 participants
		7.3 (46.92)	-0.3 (49.22)

22. Secondary Outcome

Title	Percentage Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48
Description	Blood samples were collected to perform evaluation of fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio. Baseline value is the the latest pre-dose assessment (Day 1). Percentage change from Baseline was calculated as 100 multiplied by ([post-dose visit value minus Baseline value] divided by Baseline value). Lipid last observation carried forwardd (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values. Participants on lipid-lowering agents at Baseline were excluded.
Time Frame	Baseline (Day 1) and at Weeks 24, 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Mean (Standard Deviation); Unit of Measure: Percentage change
Total/HDL Cholesterol Ratio, Week 24, n=298, 310	Number Analyzed	298 participants	310 participants
		-4.4 (22.53)	-7.5 (17.90)
Total/HDL Cholesterol Ratio, Week 48, n=298, 307	Number Analyzed	298 participants	307 participants
		-2.8 (17.86)	-4.5 (18.25)

23. Secondary Outcome

Title	Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Weeks 24, 48
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 Weeks 24 and 48 have been presented. Participants without any post-Baseline fasting LDL cholesterol value prior to Week 48 or those who had Baseline lipids-lowering agents were not included. Lipid Last Observation Carried Forward (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X in category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Measure Type: Number; Unit of Measure: Percentage of participants
Week 24, n=313, 320	Number Analyzed	313 participants	320 participants
		4	0
Week 48, n=324, 332	Number Analyzed	324 participants	332 participants
		4	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.5
	Confidence Interval	(2-Sided) 95%; 1.5 to 5.6
	Estimation Comments	Week 24

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.037
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.8
	Confidence Interval	(2-Sided) 95%; 0.2 to 5.4
	Estimation Comments	Week 48

24. Secondary Outcome

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
Description	Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200 cells/mm^3, >200 cells/mm^3 for group-1), Baseline HIV-1 RNA (<=100000, >100000 c/mL) and Race (White, African American/African heritage, Asian other).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Measure Type: Number; Unit of Measure: Percentage of participants
Baseline CD4+ cell count Group-1, <=200,n=32,26	Number Analyzed	32 participants	26 participants
		78	92
Baseline CD4+ cell count Group-1, >200,n=328,333	Number Analyzed	328 participants	333 participants
		95	94
Female, n=54, 46	Number Analyzed	54 participants	46 participants
		93	89
Male, n=306, 313	Number Analyzed	306 participants	313 participants
		94	95
Age, <35,n= 209, 203	Number Analyzed	209 participants	203 participants
		93	94
Age, 35 to <50,n=115, 122	Number Analyzed	115 participants	122 participants
		96	94
Age, >=50, n=36, 34	Number Analyzed	36 participants	34 participants
		94	91
Baseline plasma HIV-1 RNA, <=100000,n=294,282	Number Analyzed	294 participants	282 participants
		94	95
Baseline plasma HIV-1 RNA, >100000,n=66, 77	Number Analyzed	66 participants	77 participants
		92	90
Race, White, n=237,249	Number Analyzed	237 participants	249 participants
		95	95
Race, African American/African H., n=55, 40	Number Analyzed	55 participants	40 participants
		89	90
Race, Asian, n=34, 30	Number Analyzed	34 participants	30 participants
		97	90
Race, Other, n=34, 40	Number Analyzed	34 participants	40 participants
		91	93

25. Secondary Outcome

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
Description	Percentage of participants by subgroups (by age, gender, Baseline CD4+ cell count, Baseline HIV-1 RNA, race) with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. Data was presented by subgroups: age (<35, 35 to <50, >=50 years); gender (males and females), Baseline CD4+ cell count (<=200 cells/mm^3, >200 cells/mm^3 for group-1), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian and other).
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Measure Type: Number; Unit of Measure: Percentage of participants
Baseline CD4+ cell count Group-1, <=200,n=32, 26	Number Analyzed	32 participants	26 participants
		78	96
Baseline CD4+ cell count Group-1, >200,n=328,333	Number Analyzed	328 participants	333 participants
		95	94
Female, n=54, 46	Number Analyzed	54 participants	46 participants
		89	87
Male, n=306, 313	Number Analyzed	306 participants	313 participants
		94	95
Age, <35,n= 209,203	Number Analyzed	209 participants	203 participants
		92	94
Age, 35 to <50,n=115, 122	Number Analyzed	115 participants	122 participants
		97	94
Age, >=50, n=36, 34	Number Analyzed	36 participants	34 participants
		89	94
Baseline plasma HIV-1 RNA, <=100000,n=294,282	Number Analyzed	294 participants	282 participants
		92	95
Baseline plasma HIV-1 RNA, >100000,n=66, 77	Number Analyzed	66 participants	77 participants
		97	90
Race, White, n=237,249	Number Analyzed	237 participants	249 participants
		96	96
Race, African American/African H., n=55, 40	Number Analyzed	55 participants	40 participants
		80	88
Race, Asian, n=34, 30	Number Analyzed	34 participants	30 participants
		97	90
Race, Other, n=34, 40	Number Analyzed	34 participants	40 participants
		88	90

26. Secondary Outcome

Title	Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups
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 the the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the inidicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from Analysis of Covariance (ANCOVA) model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only.
Time Frame	Baseline (Day 1) and Week 48

Outcome Measure Data

Analysis Population Description

ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Least Squares Mean (Standard Error); Unit of Measure: Cells/mm^3
Baseline plasma HIV-1 RNA,<=100000, n=273,271	Number Analyzed	273 participants	271 participants
		215.6 (10.67)	208.7 (10.71)
Baseline plasma HIV-1 RNA,>100000, n=64,69	Number Analyzed	64 participants	69 participants
		261.8 (22.27)	248.7 (21.30)
Baseline CD4+ cell count,<=200, n=28, 25	Number Analyzed	28 participants	25 participants
		210.9 (33.42)	153.2 (35.29)
Baseline CD4+ cell count,>200, n=309, 315	Number Analyzed	309 participants	315 participants
		225.8 (10.00)	221.7 (9.89)
Age group-1, <35,n= 193, 191	Number Analyzed	193 participants	191 participants
		234.2 (12.67)	201.7 (12.72)
Age group-1, 35 to <50, n=112, 117	Number Analyzed	112 participants	117 participants
		212.7 (16.59)	244.2 (16.31)
Age group-1, >=50, n=32, 32	Number Analyzed	32 participants	32 participants
		209.1 (31.20)	203.9 (31.06)
Age group-2, <50,n= 305, 308	Number Analyzed	305 participants	308 participants
		226.4 (10.09)	217.8 (10.03)
Age group-2, >=50, n= 32, 32	Number Analyzed	32 participants	32 participants
		208.5 (31.27)	204.1 (31.14)
Female, n=48, 41	Number Analyzed	48 participants	41 participants
		236.2 (25.35)	263.6 (27.50)
Male, n=289, 299	Number Analyzed	289 participants	299 participants
		222.8 (10.33)	210.0 (10.17)
Race group, White, n=227, 241	Number Analyzed	227 participants	241 participants
		223.3 (11.70)	214.2 (11.38)
Race group, African Am/African H., n=45, 36	Number Analyzed	45 participants	36 participants
		214.0 (26.25)	233.7 (29.39)
Race group, Asian, n=33, 27	Number Analyzed	33 participants	27 participants
		205.0 (30.92)	189.3 (33.90)
Race group, Other, n=32, 36	Number Analyzed	32 participants	36 participants
		270.2 (31.16)	235.3 (29.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	6.9
	Confidence Interval	(2-Sided) 95%; -22.7 to 36.6
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	13.2
	Confidence Interval	(2-Sided) 95%; -46.8 to 73.2
	Estimation Comments	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.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	57.7
	Confidence Interval	(2-Sided) 95%; -37.2 to 152.5
	Estimation Comments	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.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.1
	Confidence Interval	(2-Sided) 95%; -23.5 to 31.7
	Estimation Comments	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.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	32.5
	Confidence Interval	(2-Sided) 95%; -2.7 to 67.7
	Estimation Comments	Age Group-1,<35. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-31.5
	Confidence Interval	(2-Sided) 95%; -77.1 to 14.2
	Estimation Comments	Age Group-1,35 to <50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.2
	Confidence Interval	(2-Sided) 95%; -81.4 to 91.8
	Estimation Comments	Age Group-1,>=50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-27.3
	Confidence Interval	(2-Sided) 95%; -100.8 to 46.1
	Estimation Comments	Female. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	12.8
	Confidence Interval	(2-Sided) 95%; -15.7 to 41.2
	Estimation Comments	Male. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, gender, and treatment and gender interaction.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	9.1
	Confidence Interval	(2-Sided) 95%; -22.9 to 41.1
	Estimation Comments	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.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-19.8
	Confidence Interval	(2-Sided) 95%; -97.1 to 57.6
	Estimation Comments	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.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	15.7
	Confidence Interval	(2-Sided) 95%; -74.4 to 105.9
	Estimation Comments	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.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	35.0
	Confidence Interval	(2-Sided) 95%; -49.0 to 119.0
	Estimation Comments	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.

27. Secondary Outcome

Title	Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups
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 the the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only.
Time Frame	Baseline (Day 1) and Week 24

Outcome Measure Data

Analysis Population Description

ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Arm/Group Title		DTG + 3TC	DTG + TDF/FTC
Arm/Group Description:		Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Overall Number of Participants Analyzed		360	359
Mean (Standard Error); Unit of Measure: Cells/mm^3
Baseline plasma HIV-1 RNA,<=100000, n=283,273	Number Analyzed	283 participants	273 participants
		186.01 (9.948)	148.21 (10.134)
Baseline plasma HIV-1 RNA,>100000, n=66,72	Number Analyzed	66 participants	72 participants
		193.90 (20.811)	220.71 (19.814)
Baseline CD4+ cell count,<=200, n=29, 26	Number Analyzed	29 participants	26 participants
		167.95 (31.308)	106.23 (32.990)
Baseline CD4+ cell count,>200, n=320, 319	Number Analyzed	320 participants	319 participants
		189.91 (9.362)	167.35 (9.362)
Age group, <35,n= 201, 193	Number Analyzed	201 participants	193 participants
		190.12 (11.829)	151.13 (12.050)
Age group-1, 35 to <50, n=113, 119	Number Analyzed	113 participants	119 participants
		180.50 (15.733)	190.40 (15.404)
Age group-1, >=50, n=32, 32	Number Analyzed	32 participants	32 participants
		198.74 (28.411)	133.21 (29.120)
Female, n=52, 42	Number Analyzed	52 participants	42 participants
		213.58 (23.225)	153.92 (25.910)
Male, n=297, 303	Number Analyzed	297 participants	303 participants
		183.41 (9.719)	164.18 (9.631)
Race group, White, n=233, 240	Number Analyzed	233 participants	240 participants
		182.20 (10.987)	168.30 (10.846)
Race group, African Am/African H., n=51, 39	Number Analyzed	51 participants	39 participants
		214.17 (23.472)	145.44 (26.841)
Race group, Asian, n=33, 28	Number Analyzed	33 participants	28 participants
		154.14 (29.401)	141.22 (31.663)
Race group, Other, n=32, 38	Number Analyzed	32 participants	38 participants
		222.24 (29.643)	163.05 (27.293)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	37.80
	Confidence Interval	(2-Sided) 95%; 9.98 to 65.62
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-26.81
	Confidence Interval	(2-Sided) 95%; -82.72 to 29.10
	Estimation Comments	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.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	61.72
	Confidence Interval	(2-Sided) 95%; -26.94 to 150.39
	Estimation Comments	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.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	22.57
	Confidence Interval	(2-Sided) 95%; -3.42 to 48.55
	Estimation Comments	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.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	38.99
	Confidence Interval	(2-Sided) 95%; 5.88 to 72.09
	Estimation Comments	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.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Differenc