An Efficacy, Safety, and Tolerability Study Comparing Dolutegravir Plus Lamivudine With Dolutegravir Plus Tenofovir/Emtricitabine in Treatment naïve HIV Infected Subjects (Gemini 1)

• Sponsor: ViiV Healthcare (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02831673
• Collaborator: PPD (Industry), GlaxoSmithKline (Industry)
• Enrollment: 719
• Locations: 90
• Arms: 2
• Anticipated Duration (Months): 72.2
• Patients Per Site: 8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will compare safety, efficacy, and tolerability of a two drug regimen of dolutegravir (DTG) plus (+) lamivudine (3TC) administered once daily with DTG plus two nucleoside reverse transcriptase inhibitors (Tenofovir [TDF]/Emtricitabine [FTC] fixed dose combination [FDC]) administered once daily in human immunodeficiency virus (HIV) 1 infected adult subjects that have not previously received antiretroviral therapy. The study is designed to demonstrate the non-inferior antiviral activity of DTG plus 3TC regimen to that of DTG plus TDF/FTC FDC and will characterise the long term antiviral activity, tolerability and safety of DTG plus 3TC through Week 148. Approximately, 700 subjects will be randomised 1:1 to receive DTG + 3TC or DTG + TDF/FTC FDC. Subjects will be stratified by screening HIV 1 ribonucleotide nucleic acid (RNA) levels and by screening CD4+ (cluster of differentiation 4) cell count.

Condition or Disease	Intervention/Treatment	Phase
Infection, Human Immunodeficiency Virus; HIV Infections	Drug: Dolutegravir (DTG); Drug: Lamivudine (3TC); Drug: Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC FDC)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 719 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomised, Double Blind, Multicentre, Parallel Group, Non Inferiority Study Evaluating the Efficacy, Safety, and Tolerability of Dolutegravir Plus Lamivudine Compared to Dolutegravir Plus Tenofovir/Emtricitabine in Human Immunodeficiency Virus 1 Infected Treatment naïve Adults
• Actual Study Start Date: Jul 21, 2016
• Actual Primary Completion Date: Mar 29, 2018
• Anticipated Study Completion Date: Jul 29, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DTG + 3TC (50 mg+300 mg) Eligible subjects will receive one 50 mg tablet of DTG plus one overencapsulated 300 mg 3TC tablet orally once daily upto 96 weeks; thereafter will receive DTG plus 3TC tablet upto Week 148 and will continue to receive this schedule until (i) DTG and 3TC are both locally approved for use as part of a dual regimen, and the single entities of DTG and 3TC are available to patients (e.g. through public health services), or (ii) the DTG/3TC FDC tablet, if required by local regulations, is available, , or (iii) the subject no longer derives clinical benefit, or (iv) the subject meets a protocol defined reason for discontinuation, or (v) development of the DTG plus 3TC dual regimen is terminated.	Drug: Dolutegravir (DTG); DTG is available as 50 mg white, round, biconvex, film coated tablet debossed on one side with 'SV 572' and on the other side with '50'. The tablets are packaged into high density polyethylene (HDPE) bottles with induction seals and child resistant closures. Each 45 ml bottle contains 30 tablets and a desiccant. DTG 50 mg tablet will be orally administered once daily with or without food upto 148 weeks.; Drug: Lamivudine (3TC); Lamivudine is available as swedish orange, 'AA' sized elongated double blind HPMC capsules containing 300 mg lamivudine to visually match overencapsulated TDF/FTC FDC tablet. The capsules are packaged into HDPE bottles with induction seals and child resistant closures. Each 150 mL bottle contains 30 capsules and a desiccant. Overencapsulated 3TC 300 mg tablet will be orally administered once daily with or without food upto 96 weeks. From Week 96 to Week 148, lamivudine will be dispensed as 300 mg white, diamond shaped, scored, film coated tablets debossed with 'GX CJ7' on both sides, packed in over labelled HDPE bottles with child-resistant closures each containing 30 tablets.
Active Comparator: DTG + TDF/FTC FDC (50 mg+300/200 mg) Eligible subjects will receive one 50 mg tablet of DTG plus one overencapsulated TDF/ FTC FDC (300/200 mg) tablet orally once daily upto 96 weeks; thereafter will receive DTG plus TDF/FTC FDC tablets upto Week 148 (open-label randomised phase).	Drug: Dolutegravir (DTG); DTG is available as 50 mg white, round, biconvex, film coated tablet debossed on one side with 'SV 572' and on the other side with '50'. The tablets are packaged into high density polyethylene (HDPE) bottles with induction seals and child resistant closures. Each 45 ml bottle contains 30 tablets and a desiccant. DTG 50 mg tablet will be orally administered once daily with or without food upto 148 weeks.; Drug: Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC FDC); Tenofovir disoproxil fumarate and Emtricitabine are available as swedish orange, 'AA' sized elongated double blind HPMC capsules containing 300 mg TDF and 200 mg FTC to visually match overencapsulated 3TC tablet. The capsules are packaged into HDPE bottles with induction seals and child resistant closures. Each 150 mL bottle contains 30 capsules and a desiccant. Overencapsulated tenofovir disoproxil fumarate/emtricitabine tablet will be orally administered once daily with or without food upto 96 weeks. From Week 96 to Week 148, tenofovir disoproxil fumarate/emtricitabine will be dispensed as 300/200 mg white, blue, capsule shaped, film coated tablets debossed with 'GILEAD' on one side and '701' on another side, packed in overlabelled HDPE bottles with polypropylene childresistant closures each containing 30 tablets and a desiccant.

Outcome Measures

Primary Outcome Measures

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

   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 receive at least one dose of study treatment.

Secondary Outcome Measures

1. Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24 [Week 24]

   Percentage of participants with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. This endpoint was analyzed using a stratified analysis with Cochran-Mantel-Haenszel weights.

2. Time to Viral Suppression (HIV-1 RNA <50 c/mL) [Up to Week 48]

   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 interquartile range (first Quartile and third Quartile) have been presented.

3. CD4+ Cell Counts at Weeks 24 and 48 [Weeks 24 and 48]

   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.

4. Changes From Baseline in CD4+ Cell Counts at Week 24 and 48 [Baseline (Day 1) and Weeks 24, 48]

   CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is defined as the the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for the following covariates/factors: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction, and Baseline CD4+ cell count and visit interaction, with visit as the repeated factor.

5. Number of Participants With HIV-1 Disease Progression [Up to Week 48]

   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 progression summarize participants who had HIV infection stage 3 associated conditions or death. Indicators of clinical disease progression were defined as: CDC Category Stage 1 at enrolment to Stage 3 event; CDC Category Stage 2 at enrolment to Stage 3 event; CDC Category Stage 3 at enrolment to New Stage 3 Event; CDC Category Stage 1, 2 or 3 at enrolment to Death.

6. Number of Participants With Treatment-emergent Genotypic Resistance [Up to Week 48]

   Number of participants, who meet confirmed virologic withdrawal (CVW) criteria, with treatment emergent phenotypic 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.

7. Number of Participants With Treatment-emergent Phenotypic Resistance [Up to Week 48]

   Number of participants, who meet CVW criteria, with treatment emergent phenotypic resistance to INSTI and/or NRTI were summarized. Assessment of antiviral activity of anti-retroviral therapy (ART) using phenotypic test results was interpreted through a proprietary algorithm (from Monogram Biosciences) and provides the overall susceptibility of the drug. Partially sensitive and resistant calls were considered resistant in this analysis. 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.

8. Number of Participants With Any Adverse Event (AE) and Serious AE (SAE) [Up to Week 48]

   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.

9. Number of Participants With AEs by Their Severity Grades [Up to Week 48]

   An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented.

10. Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade [Up to Week 48]

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Adverse events were evaluated by the investigator and graded according to the DAIDS toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with drug related AEs and drug related AEs by maximum grade have been presented.

11. Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities [Up to Week 48]

    Blood samples were collected up to Week 48 for assessment of hematology parameters to assess any abnormality per toxicity scales for platelet count, neutrophils, hemoglobin. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent hematology toxicities in any of the hematology parameters have been presented.

12. Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities [Up to Week 48]

    Blood samples were collected up to Week 48 for assessment of Alanine Aminotransferase (ALT), Aspartate aminotransferase (AST), Creatinine, Glucose, Potassium, Sodium, Chloride, Calcium, Total carbon dioxide (CO2), Alkaline phosphatase (ALP), Phosphate, Total bilirubin, Total protein, Albumin, Creatine phosphokinase (CPK), Creatinine clearance,Glomerular filtration rate (GFR), Total cholesterol, High density lipoprotein (HDL), Low density lipoprotein (LDL), Triglyceride and Lipase. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent chemistry toxicities in any of the chemistry parameters have been presented.

13. Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48 [Up to Week 48]

    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. Data cut-off dates for analysis at Week 24 and Week 48 were 19-Jan-2018 and 22-May-2018 respectively. Number of participants who discontinued treatment due to AEs have been reported.

14. Change From Baseline in Renal Biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48 [Baseline and at Weeks 24, 48]

    Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers which included Serum Cystatin C and Serum Retinol Binding Protein (RBP). Baseline value is the latest pre-dose assessment. Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

15. 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 [Baseline and at Weeks 24, 48]

    Blood and/or urine were collected to perform evaluation of renal inflammation 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 post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

16. Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Weeks 24, 48 [Baseline and at Weeks 24, 48]

    Blood and/or urine were collected to perform evaluation of renal inflammation biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.

17. 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 [Baseline and at Weeks 24, 48]

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

18. 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 [Baseline and at Weeks 24, 48]

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

19. Change From Baseline in Bone Biomarker-Serum Vitamin D at Weeks 24, 48 [Baseline and at Weeks 24, 48]

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

20. Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48 [Baseline (Day 1) and at Weeks 24, 48]

    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).

21. Percentage Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48 [Baseline (Day 1) and at Weeks 24, 48]

    Blood samples were collected to perform evaluation of fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio. Baseline value is the latest pre-dose assessment (Day 1). Percentage change from Baseline was calculated as 100 multiplied by ([post-dose visit value minus Baseline value] divided by Baseline value).

22. Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Weeks 24, 48 [Up to Week 48]

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

23. 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 [Week 24]

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

24. 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 [Week 48]

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

25. Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups [Baseline (Day 1) and Week 48]

    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 latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented 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.

26. Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups [Baseline (Day 1) and Week 24]

    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 latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age, 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.

27. Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Utility Score at Weeks 4, 24, 48 [Baseline and Weeks 4, 24, 48]

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

28. Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24 48 [Baseline (Day 1) and Weeks 4, 24, 48]

    EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). MMRM was run on the LOCF dataset, using the observed margins (OM) option. Baseline was the latest pre-dose assessment value and change from Baseline=post-dose value minus Baseline value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must be an HIV 1 infected adult >=18 years of age (or older, if required by local regulations) at the time of signing the informed consent

• An eligible female subject should not be pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at Screening and negative urine test at Baseline), not lactating, and at least one of the following conditions applies

• Non reproductive premenopausal women are those that have undergone documented tubal ligation or documented hysteroscopic tubal occlusion procedure with follow up confirmation of bilateral tubal occlusion or documented bilateral oophorectomy or hysterectomy

• Non reproductive premenopausal women are those with 12 months of spontaneous amenorrhea and >=45 years of age

• Women with reproductive potential agree to follow one of the protocol-defined methods for avoiding pregnancy

• Should have screening plasma HIV 1 RNA levels of 1000 c/mL to <=100,000 c/mL. If an independent review of accumulated data from other clinical trials investigating the DTG plus 3TC dual regimen is supportive of the DTG plus 3TC treatment regimen, enrolment will be opened to subjects with Screening plasma HIV 1 RNA of 1000 c/mL to <=500,000 c/mL

• Subject should be antiretroviral naïve (defined as <=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV 1 infection). Subjects who received HIV post exposure prophylaxis (PEP) or pre exposure prophylaxis (PrEP) in the past are allowed as long as the last PEP/PrEP dose was >1 year from HIV diagnosis or there is documented HIV seronegativity between the last prophylactic dose and the date of HIV diagnosis

• Subject or the subject's legal representative capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and the protocol

• Subjects enrolled in France: a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category

Exclusion Criteria

• Women who are breastfeeding or plan to become pregnant or breastfeed during the study

• Any evidence of an active centers for disease control and prevention (CDC) Stage 3 disease (CDC, 2014), except cutaneous Kaposi's sarcoma not requiring systemic therapy and historical or current CD4 cell counts less than 200 cells/mm^3

• Subjects with severe hepatic impairment (Class C) as determined by Child Pugh classification

• Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones

• Evidence of hepatitis B virus (HBV) infection or HBV surface antibody (anti-HBs or

HBsAb) based on:

Subjects positive for HBV surface antigen (HBsAg) at screening will be excluded Subjects negative for HBV core antibody (anti HBs) but positive for anti HBc (negative HBsAg status) and positive for HBV deoxyribose nucleic acid (DNA) will be excluded; however, subjects positive for anti HBc (negative HBsAg status) and positive for anti HBs (past and/or current evidence) are immune to HBV and will not be excluded

• Anticipated need for any hepatitis B virus (HCV) therapy during the first 48 weeks of the study and for HCV therapy based on interferon or any drugs that have a potential for adverse drug:drug interactions with study treatment throughout the entire study period

• Untreated syphilis infection positive RPR at Screening without clear documentation of treatment. Subjects who are at least 14 days post completed treatment are eligible

• History or presence of allergy or intolerance to the study drugs or their components or drugs of their class

• Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; other localised malignancies require agreement between the investigator and the Study Medical Monitor for inclusion of the subject

• Subjects who in the Investigator's judgment, poses a significant suicidality risk. Recent history of suicidal behaviour and/or suicidal ideation may be considered as evidence of serious suicide risk

• Treatment with an HIV 1 immunotherapeutic vaccine within 90 days of Screening

• Treatment with any of the following agents within 28 days of Screening:

• Radiation therapy,

• Cytotoxic chemotherapeutic agents,

• Any systemic immune suppressant

• Treatment with any agent, except recognised ART as allowed above, with documented activity against HIV 1 in vitro within 28 days of first dose of study treatment

• Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of study treatment

• Subjects enrolled in France: the subject has participated in any study using an investigational drug during the previous 60 days or 5 half lives, or twice the duration of the biological effect of the experimental drug or vaccine, whichever is longer, prior to screening for the study or the subject will participate simultaneously in another clinical study

• Any evidence of pre existing viral resistance based on the presence of any major resistance associated mutation in the Screening result or, if known, in any historical resistance test result

• Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening period to verify a result

• Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound

• Alanine aminotransferase (ALT) >=5 times the upper limit of normal (ULN) or ALT

=3xULN and bilirubin >=1.5xULN (with >35% direct bilirubin)

• Creatinine clearance of <50 mL/min per 1.73 m^2 via the chronic kidney disease epidemiology collaboration (CKD EPI) method

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Phoenix	Arizona	United States	85015
2	GSK Investigational Site	Washington	District of Columbia	United States	20037
3	GSK Investigational Site	Fort Pierce	Florida	United States	34982
4	GSK Investigational Site	Orlando	Florida	United States	32806
5	GSK Investigational Site	West Palm Beach	Florida	United States	33407
6	GSK Investigational Site	Decatur	Georgia	United States	30033
7	GSK Investigational Site	Indianapolis	Indiana	United States	46202
8	GSK Investigational Site	Springfield	Massachusetts	United States	01199
9	GSK Investigational Site	Berkley	Michigan	United States	48072
10	GSK Investigational Site	Kansas City	Missouri	United States	64111
11	GSK Investigational Site	Saint Louis	Missouri	United States	63108
12	GSK Investigational Site	Chapel Hill	North Carolina	United States	27599-7064
13	GSK Investigational Site	Allentown	Pennsylvania	United States	18102
14	GSK Investigational Site	Providence	Rhode Island	United States	02906
15	GSK Investigational Site	Bellaire	Texas	United States	77401
16	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1181ACH
17	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires	Argentina	C1405CKC
18	GSK Investigational Site	Buenos Aires		Argentina	1141
19	GSK Investigational Site	Buenos Aires		Argentina	1202
20	GSK Investigational Site	Darlinghurst	New South Wales	Australia	2010
21	GSK Investigational Site	Sydney	New South Wales	Australia	2010
22	GSK Investigational Site	Fortitude Valley	Queensland	Australia	4006
23	GSK Investigational Site	Antwerpen		Belgium	2000
24	GSK Investigational Site	Brussels		Belgium	1000
25	GSK Investigational Site	Brussels		Belgium	1070
26	GSK Investigational Site	Bruxelles		Belgium	1200
27	GSK Investigational Site	Ottawa	Ontario	Canada	K1H 8L6
28	GSK Investigational Site	Montreal	Quebec	Canada	H2L 4E9
29	GSK Investigational Site	Montreal	Quebec	Canada	H2L 4P9
30	GSK Investigational Site	Le Kremlin-Bicetre Cedex		France	94275
31	GSK Investigational Site	Marseille		France	13003
32	GSK Investigational Site	Paris Cedex 10		France	75475
33	GSK Investigational Site	Paris Cedex 12		France	75571
34	GSK Investigational Site	Paris		France	75013
35	GSK Investigational Site	Toulouse Cedex 9		France	31059
36	GSK Investigational Site	Muenchen	Bayern	Germany	80336
37	GSK Investigational Site	Bonn	Nordrhein-Westfalen	Germany	53127
38	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45122
39	GSK Investigational Site	Berlin		Germany	10439
40	GSK Investigational Site	Hamburg		Germany	20146
41	GSK Investigational Site	Bologna	Emilia-Romagna	Italy	40138
42	GSK Investigational Site	Ferrara	Emilia-Romagna	Italy	44100
43	GSK Investigational Site	Genova	Liguria	Italy	16132
44	GSK Investigational Site	Brescia	Lombardia	Italy	25123
45	GSK Investigational Site	Busto Arsizio (VA)	Lombardia	Italy	21052
46	GSK Investigational Site	Milano	Lombardia	Italy	20127
47	GSK Investigational Site	Pavia	Lombardia	Italy	27100
48	GSK Investigational Site	Padova		Italy	35128
49	GSK Investigational Site	Reggio Emilia		Italy	42121
50	GSK Investigational Site	Roma		Italy	00149
51	GSK Investigational Site	Busan		Korea, Republic of	49241
52	GSK Investigational Site	Daegu		Korea, Republic of	41944
53	GSK Investigational Site	Seoul		Korea, Republic of	137-701
54	GSK Investigational Site	Seoul		Korea, Republic of	152-703
55	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44160
56	GSK Investigational Site	Zapopan	Jalisco	Mexico	45170
57	GSK Investigational Site	Distrito Federal		Mexico	06470
58	GSK Investigational Site	Rotterdam		Netherlands	3015 CE
59	GSK Investigational Site	Rotterdam		Netherlands	3079 DZ
60	GSK Investigational Site	Coimbra		Portugal	3000-075
61	GSK Investigational Site	Lisboa		Portugal	1169-050
62	GSK Investigational Site	Porto		Portugal	4369-004
63	GSK Investigational Site	Cluj-Napoca		Romania	400348
64	GSK Investigational Site	Galati		Romania	800179
65	GSK Investigational Site	Ekaterinburg		Russian Federation	620149
66	GSK Investigational Site	Krasnojarsk		Russian Federation	660049
67	GSK Investigational Site	Moscow		Russian Federation	105275
68	GSK Investigational Site	Orel		Russian Federation	302040
69	GSK Investigational Site	St. Petersburg		Russian Federation	196645
70	GSK Investigational Site	Toliyatti		Russian Federation	445846
71	GSK Investigational Site	Observatory, Cape Town		South Africa	7925
72	GSK Investigational Site	Alicante		Spain	03010
73	GSK Investigational Site	Badalona		Spain	08916
74	GSK Investigational Site	Córdoba		Spain	14004
75	GSK Investigational Site	Elche (Alicante)		Spain	03203
76	GSK Investigational Site	Madrid		Spain	28007
77	GSK Investigational Site	Madrid		Spain	28031
78	GSK Investigational Site	Madrid		Spain	28034
79	GSK Investigational Site	Madrid		Spain	28911
80	GSK Investigational Site	Mataró		Spain	08304
81	GSK Investigational Site	San Sebastian		Spain	20080
82	GSK Investigational Site	Santiago de Compostela		Spain	15706
83	GSK Investigational Site	Valencia		Spain	46014
84	GSK Investigational Site	Vigo		Spain	36312
85	GSK Investigational Site	Kaohsiung		Taiwan	824
86	GSK Investigational Site	Taipei		Taiwan	100
87	GSK Investigational Site	Taipei		Taiwan	11217
88	GSK Investigational Site	London		United Kingdom	SE1 9RT
89	GSK Investigational Site	London		United Kingdom	SW10 9NH
90	GSK Investigational Site	Manchester		United Kingdom	M8 5RB

Sponsors and Collaborators

• ViiV Healthcare
• PPD
• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, ViiV Healthcare

Study Documents (Full-Text)

• Study Protocol - Dec 1, 2017
• Statistical Analysis Plan - Jan 4, 2018

More Information

Publications

• Cahn P, Madero JS, Arribas JR, Antinori A, Ortiz R, Clarke AE, Hung CC, Rockstroh JK, Girard PM, Sievers J, Man C, Currie A, Underwood M, Tenorio AR, Pappa K, Wynne B, Fettiplace A, Gartland M, Aboud M, Smith K; GEMINI Study Team. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet. 2019 Jan 12;393(10167):143-155. doi: 10.1016/S0140-6736(18)32462-0. Epub 2018 Nov 9. Erratum in: Lancet. 2018 Nov 28;:.

• Responsible Party: ViiV Healthcare
• ClinicalTrials.gov Identifier: NCT02831673
• Other Study ID Numbers: 204861; 2015-004418-95
• First Posted: Jul 13, 2016
• Last Update Posted: Jul 14, 2022
• Last Verified: Jun 1, 2022

• Keywords provided by ViiV Healthcare: safety; treatment naïve; HIV 1; dolutegravir plus lamivudine; non inferiority; tolerability; dolutegravir plus tenofovir/emtricitabine; efficacy
• Additional relevant MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Tenofovir; Lamivudine; Emtricitabine; Dolutegravir

Study Results

Participant Flow

Recruitment Details	This study is a randomized, double-blind, parallel-group, non-inferiority study. A total of 87 investigational centers in 18 countries randomized one or more participants. The results are presented based on primary analysis at Week 48. Analysis presented used a data cut-off date of 22-May-2018 (for Week 48 database freeze).
Pre-assignment Detail	Total of 719 participants were enrolled and randomized, however only 714 were dosed in the study and 5 were not dosed due to physician decision (3), protocol deviation (1) and participant's own decision (1).

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Period Title: Overall Study
STARTED	356	358
COMPLETED	0	0
NOT COMPLETED	356	358

Baseline Characteristics

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC	Total
Arm/Group Description	Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.	Total of all reporting groups
Overall Participants	356	358	714
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	34.0 (9.88)	35.0 (10.72)	34.5 (10.31)
Sex: Female, Male (Count of Participants)
Female	59 16.6%	52 14.5%	111 15.5%
Male	297 83.4%	306 85.5%	603 84.5%
Race/Ethnicity, Customized (Count of Participants)
American (Am) Indian or Alaska (Al.) native	28 7.9%	28 7.8%	56 7.8%
Asian-Central/South Asian heritage (H.)	0 0%	4 1.1%	4 0.6%
Asian - East Asian H.	33 9.3%	36 10.1%	69 9.7%
Asian - South East Asian H.	4 1.1%	2 0.6%	6 0.8%
Black or African Am	44 12.4%	36 10.1%	80 11.2%
Native Hawaiian or other Pacific Islander	2 0.6%	0 0%	2 0.3%
White (Wt)-Arabic/North African H.	5 1.4%	6 1.7%	11 1.5%
Wt-Wt/Caucasian (Ca.)/European (Eu.) H.	238 66.9%	242 67.6%	480 67.2%
Black or African Am and Am Indian or Al. native	0 0%	1 0.3%	1 0.1%
Black or African Am and Wt-Wt/Ca./Eu. H.	1 0.3%	1 0.3%	2 0.3%
Am Indian or Al. native and Wt-Wt/Ca./Eu. H.	1 0.3%	2 0.6%	3 0.4%

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 receive 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Number (95% Confidence Interval) [Percentage of participants]	90 25.3%	93 26%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	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 greater than -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted difference in proportion
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95%; -6.7 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in proportion was based on CMH stratified analysis adjusting for Baseline stratification factors: Plasma HIV-1 RNA (<=versus [vs.]>100,000 c/mL) and cluster of differentiation 4+ (CD4+) cell count (<= vs. >200 cells per cubic millimeter).

2. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 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 Cochran-Mantel-Haenszel 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Number (95% Confidence Interval) [Percentage of participants]	92 25.8%	93 26%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted difference in proportion
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -4.2 to 3.4
	Parameter Dispersion	Type: Value:
	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 per cubic millimeter).

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 interquartile range (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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Median (Inter-Quartile Range) [Days]	29.0	29.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.558
	Comments	The generalized Wilcoxon procedure was used to estimate a p-value for detecting a difference in cumulative incidence curves between treatment groups.
	Method	Generalized Wilcoxon procedure
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios were estimated using the Cox proportional hazard regression model. A hazard ratio of >1 indicates that DTG + 3TC is more likely to reach viral suppression earlier than DTG + TDF/FTC.

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+. It was evaluated 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Week 24, n=340,341	655.3 (288.32)	632.8 (262.61)
Week 48, n=324,334	687.7 (275.47)	675.3 (274.46)

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+. It was evaluated by flow cytometry. Baseline value is defined as the the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for the following covariates/factors: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction, and Baseline CD4+ cell count and visit interaction, with visit as the repeated factor.
Time Frame	Baseline (Day 1) 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Week 24, n=340,341	192.2 (9.67)	175.1 (9.41)
Week 48, n=324,334	222.2 (9.87)	217.7 (10.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.206
	Comments
	Method	Mixed Model Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	17.1
	Confidence Interval	(2-Sided) 95%; -9.4 to 43.6
	Parameter Dispersion	Type: Value:
	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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.754
	Comments
	Method	Mixed Model Repeated Measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.6
	Confidence Interval	(2-Sided) 95%; -23.9 to 33.0
	Parameter Dispersion	Type: Value:
	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 progression summarize participants who had HIV infection stage 3 associated conditions or death. Indicators of clinical disease progression were defined as: CDC Category Stage 1 at enrolment to Stage 3 event; CDC Category Stage 2 at enrolment to Stage 3 event; CDC Category Stage 3 at enrolment 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
No HIV-1 disease progression	352 98.9%	356 99.4%
From CDC Stage 1 to CDC Stage 3 Event	0 0%	0 0%
From CDC Stage 2 to CDC Stage 3 Event	2 0.6%	2 0.6%
From CDC Stage 3 to New CDC Stage 3 Event	2 0.6%	0 0%
From CDC Stage 1, 2 or 3 to Death	0 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 phenotypic 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. Only those participants available at the specified time points were analyzed.

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	4	2
INSTI Mutations	0 0%	0 0%
Major mutations of NRTI	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 was interpreted through a proprietary algorithm (from Monogram Biosciences) and provides the overall susceptibility of the drug. Partially sensitive and resistant calls were considered resistant in this analysis. 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.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Viral Phenotypic 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	4	2
INSTI, DTG, Sensitive, n=4,1	4 1.1%	1 0.3%
INSTI, DTG, Resistant, n=4,1	0 0%	0 0%
INSTI, EVG, Sensitive, n=4,1	4 1.1%	1 0.3%
INSTI, EVG, Resistant, n=4,1	0 0%	0 0%
INSTI, RAL, Sensitive, n=4,1	4 1.1%	1 0.3%
INSTI, RAL, Resistant, n=4,1	0 0%	0 0%
NRTI, 3TC, Sensitive, n=4,2	4 1.1%	2 0.6%
NRTI, 3TC, Resistant, n=4,2	0 0%	0 0%
NRTI, ABC, Sensitive, n=4,2	4 1.1%	2 0.6%
NRTI, ABC, Resistant, n=4,2	0 0%	0 0%
NRTI, AZT, Sensitive, n=4,2	4 1.1%	2 0.6%
NRTI, AZT, Resistant, n=4,2	0 0%	0 0%
NRTI, D4T, Sensitive, n=4,2	4 1.1%	2 0.6%
NRTI, D4T, Resistant, n=4,2	0 0%	0 0%
NRTI, DDI, Sensitive, n=4,2	4 1.1%	2 0.6%
NRTI, DDI, Resistant, n=4,2	0 0%	0 0%
NRTI, FTC, Sensitive, n=4,2	4 1.1%	2 0.6%
NRTI, FTC, Resistant, n=4,2	0 0%	0 0%
NRTI, TDF, Sensitive, n=4,2	4 1.1%	2 0.6%
NRTI, TDF, Resistant, n=4,2	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.
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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Any AE	276 77.5%	295 82.4%
Any SAE	21 5.9%	22 6.1%

10. Secondary Outcome

Title	Number of Participants With AEs by Their 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. Adverse events were evaluated by the investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented.
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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Grade 1 AEs	60 16.9%	61 17%
Grade 2 AEs	195 54.8%	210 58.7%
Grade 3 AEs	19 5.3%	22 6.1%
Grade 4 AEs	2 0.6%	2 0.6%
Grade 5 AEs	0 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. Adverse events were evaluated by the investigator and graded according to the DAIDS toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with drug related AEs and drug related AEs by maximum grade 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Any drug related AE	71 19.9%	94 26.3%
Drug related AEs with maximum toxicity Grade 1	50 14%	69 19.3%
Drug related AEs with maximum toxicity Grade 2	18 5.1%	22 6.1%
Drug related AEs with maximum toxicity Grade 3	3 0.8%	3 0.8%
Drug related AEs with maximum toxicity Grade 4	0 0%	0 0%
Drug related AEs with maximum toxicity Grade 5	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 hematology parameters to assess any abnormality per toxicity scales for platelet count, neutrophils, hemoglobin. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent hematology toxicities in any of the 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Hemoglobin, Grades 1 to 4	7 2%	5 1.4%
Hemoglobin, Grades 2 to 4	1 0.3%	1 0.3%
Hemoglobin, Grades 3 to 4	0 0%	0 0%
Hemoglobin, Grade 1	6 1.7%	4 1.1%
Hemoglobin, Grade 2	1 0.3%	1 0.3%
Hemoglobin, Grade 3	0 0%	0 0%
Hemoglobin, Grade 4	0 0%	0 0%
Leukocytes, Grades 1 to 4	5 1.4%	3 0.8%
Leukocytes, Grades 2 to 4	2 0.6%	2 0.6%
Leukocytes, Grades 3 to 4	0 0%	0 0%
Leukocytes, Grade 1	3 0.8%	1 0.3%
Leukocytes, Grade 2	2 0.6%	2 0.6%
Leukocytes, Grade 3	0 0%	0 0%
Leukocytes, Grade 4	0 0%	0 0%
Neutrophils, Grades 1 to 4	16 4.5%	12 3.4%
Neutrophils, Grades 2 to 4	10 2.8%	5 1.4%
Neutrophils, Grades 3 to 4	3 0.8%	2 0.6%
Neutrophils, Grade 1	6 1.7%	7 2%
Neutrophils, Grade 2	7 2%	3 0.8%
Neutrophils, Grade 3	2 0.6%	2 0.6%
Neutrophils, Grade 4	1 0.3%	0 0%
Platelets, Grades 1 to 4	9 2.5%	9 2.5%
Platelets, Grades 2 to 4	3 0.8%	4 1.1%
Platelets, Grades 3 to 4	0 0%	1 0.3%
Platelets, Grade 1	6 1.7%	5 1.4%
Platelets, Grade 2	3 0.8%	3 0.8%
Platelets, Grade 3	0 0%	1 0.3%
Platelets, Grade 4	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), Creatinine, Glucose, Potassium, Sodium, Chloride, Calcium, Total carbon dioxide (CO2), Alkaline phosphatase (ALP), Phosphate, Total bilirubin, Total protein, Albumin, Creatine phosphokinase (CPK), Creatinine clearance,Glomerular filtration rate (GFR), Total cholesterol, High density lipoprotein (HDL), Low density lipoprotein (LDL), Triglyceride and Lipase. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent chemistry toxicities in any of the chemistry parameters have been presented.
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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
ALT, Grades 1 to 4	31 8.7%	48 13.4%
ALT, Grades 2 to 4	14 3.9%	16 4.5%
ALT, Grades 3 to 4	9 2.5%	8 2.2%
ALT, Grade 1	17 4.8%	32 8.9%
ALT, Grade 2	5 1.4%	8 2.2%
ALT, Grade 3	4 1.1%	3 0.8%
ALT, Grade 4	5 1.4%	5 1.4%
Albumin, Grades 1 to 4	1 0.3%	1 0.3%
Albumin, Grades 2 to 4	1 0.3%	0 0%
Albumin, Grades 3 to 4	0 0%	0 0%
Albumin, Grade 1	0 0%	1 0.3%
Albumin, Grade 2	1 0.3%	0 0%
Albumin, Grade 3	0 0%	0 0%
Albumin, Grade 4	0 0%	0 0%
ALP, Grades 1 to 4	7 2%	7 2%
ALP, Grades 2 to 4	3 0.8%	1 0.3%
ALP, Grades 3 to 4	0 0%	0 0%
ALP, Grade 1	4 1.1%	6 1.7%
ALP, Grade 2	3 0.8%	1 0.3%
ALP, Grade 3	0 0%	0 0%
ALP, Grade 4	0 0%	0 0%
AST, Grades 1 to 4	35 9.8%	51 14.2%
AST, Grades 2 to 4	17 4.8%	20 5.6%
AST, Grades 3 to 4	5 1.4%	12 3.4%
AST, Grade 1	18 5.1%	31 8.7%
AST, Grade 2	12 3.4%	8 2.2%
AST, Grade 3	4 1.1%	8 2.2%
AST, Grade 4	1 0.3%	4 1.1%
Bilirubin, Grades 1 to 4	28 7.9%	37 10.3%
Bilirubin, Grades 2 to 4	8 2.2%	13 3.6%
Bilirubin, Grades 3 to 4	4 1.1%	4 1.1%
Bilirubin, Grade 1	20 5.6%	24 6.7%
Bilirubin, Grade 2	4 1.1%	9 2.5%
Bilirubin, Grade 3	2 0.6%	4 1.1%
Bilirubin, Grade 4	2 0.6%	0 0%
CO2, Grades 1 to 4	99 27.8%	81 22.6%
CO2, Grades 2 to 4	7 2%	6 1.7%
CO2, Grades 3 to 4	0 0%	0 0%
CO2, Grade 1	92 25.8%	75 20.9%
CO2, Grade 2	7 2%	6 1.7%
CO2, Grade 3	0 0%	0 0%
CO2, Grade 4	0 0%	0 0%
Cholesterol, Grades 1 to 4	55 15.4%	27 7.5%
Cholesterol, Grades 2 to 4	19 5.3%	9 2.5%
Cholesterol, Grades 3 to 4	0 0%	0 0%
Cholesterol, Grade 1	36 10.1%	18 5%
Cholesterol, Grade 2	19 5.3%	9 2.5%
Cholesterol, Grade 3	0 0%	0 0%
Cholesterol, Grade 4	0 0%	0 0%
CPK, Grades 1 to 4	42 11.8%	40 11.2%
CPK, Grades 2 to 4	24 6.7%	28 7.8%
CPK, Grades 3 to 4	13 3.7%	18 5%
CPK, Grade 1	18 5.1%	12 3.4%
CPK, Grade 2	11 3.1%	10 2.8%
CPK, Grade 3	8 2.2%	11 3.1%
CPK, Grade 4	5 1.4%	7 2%
Creatinine, Grades 1 to 4	15 4.2%	22 6.1%
Creatinine, Grades 2 to 4	1 0.3%	2 0.6%
Creatinine, Grades 3 to 4	0 0%	1 0.3%
Creatinine, Grade 1	14 3.9%	20 5.6%
Creatinine, Grade 2	1 0.3%	1 0.3%
Creatinine, Grade 3	0 0%	1 0.3%
Creatinine, Grade 4	0 0%	0 0%
Direct Bilirubin, Grades 1 to 4	10 2.8%	9 2.5%
Direct Bilirubin, Grades 2 to 4	10 2.8%	9 2.5%
Direct Bilirubin, Grades 3 to 4	10 2.8%	9 2.5%
Direct Bilirubin, Grade 1	0 0%	0 0%
Direct Bilirubin, Grade 2	0 0%	0 0%
Direct Bilirubin, Grade 3	10 2.8%	9 2.5%
Direct Bilirubin, Grade 4	0 0%	0 0%
GFR, Grades 1 to 4	151 42.4%	185 51.7%
GFR, Grades 2 to 4	151 42.4%	185 51.7%
GFR, Grades 3 to 4	9 2.5%	18 5%
GFR, Grade 1	0 0%	0 0%
GFR, Grade 2	142 39.9%	167 46.6%
GFR, Grade 3	9 2.5%	17 4.7%
GFR, Grade 4	0 0%	1 0.3%
Hypercalcaemia, Grades 1 to 4	3 0.8%	2 0.6%
Hypercalcaemia, Grades 2 to 4	0 0%	0 0%
Hypercalcaemia, Grades 3 to 4	0 0%	0 0%
Hypercalcaemia, Grade 1	3 0.8%	2 0.6%
Hypercalcaemia, Grade 2	0 0%	0 0%
Hypercalcaemia, Grade 3	0 0%	0 0%
Hypercalcaemia, Grade 4	0 0%	0 0%
Hyperglycemia, Grades 1 to 4	59 16.6%	50 14%
Hyperglycemia, Grades 2 to 4	23 6.5%	13 3.6%
Hyperglycemia, Grades 3 to 4	3 0.8%	2 0.6%
Hyperglycemia, Grade 1	36 10.1%	37 10.3%
Hyperglycemia, Grade 2	20 5.6%	11 3.1%
Hyperglycemia, Grade 3	3 0.8%	2 0.6%
Hyperglycemia, Grade 4	0 0%	0 0%
Hyperkalemia, Grades 1 to 4	0 0%	0 0%
Hyperkalemia, Grades 2 to 4	0 0%	0 0%
Hyperkalemia, Grades 3 to 4	0 0%	0 0%
Hyperkalemia, Grade 1	0 0%	0 0%
Hyperkalemia, Grade 2	0 0%	0 0%
Hyperkalemia, Grade 3	0 0%	0 0%
Hyperkalemia, Grade 4	0 0%	0 0%
Hypernatremia, Grades 1 to 4	3 0.8%	0 0%
Hypernatremia, Grades 2 to 4	0 0%	0 0%
Hypernatremia, Grades 3 to 4	0 0%	0 0%
Hypernatremia, Grade 1	3 0.8%	0 0%
Hypernatremia, Grade 2	0 0%	0 0%
Hypernatremia, Grade 3	0 0%	0 0%
Hypernatremia, Grade 4	0 0%	0 0%
Hypocalcaemia, Grades 1 to 4	9 2.5%	3 0.8%
Hypocalcaemia, Grades 2 to 4	1 0.3%	0 0%
Hypocalcaemia, Grades 3 to 4	0 0%	0 0%
Hypocalcaemia, Grade 1	8 2.2%	3 0.8%
Hypocalcaemia, Grade 2	1 0.3%	0 0%
Hypocalcaemia, Grade 3	0 0%	0 0%
Hypocalcaemia, Grade 4	0 0%	0 0%
Hypoglycemia, Grades 1 to 4	13 3.7%	13 3.6%
Hypoglycemia, Grades 2 to 4	7 2%	3 0.8%
Hypoglycemia, Grades 3 to 4	2 0.6%	1 0.3%
Hypoglycemia, Grade 1	6 1.7%	10 2.8%
Hypoglycemia, Grade 2	5 1.4%	12 3.4%
Hypoglycemia, Grade 3	1 0.3%	0 0%
Hypoglycemia, Grade 4	1 0.3%	1 0.3%
Hypokalemia, Grades 1 to 4	2 0.6%	5 1.4%
Hypokalemia, Grades 2 to 4	0 0%	1 0.3%
Hypokalemia, Grades 3 to 4	0 0%	0 0%
Hypokalemia, Grade 1	2 0.6%	4 1.1%
Hypokalemia, Grade 2	0 0%	1 0.3%
Hypokalemia, Grade 3	0 0%	0 0%
Hypokalemia, Grade 4	0 0%	0 0%
Hyponatremia, Grades 1 to 4	19 5.3%	21 5.9%
Hyponatremia, Grades 2 to 4	1 0.3%	0 0%
Hyponatremia, Grades 3 to 4	0 0%	0 0%
Hyponatremia, Grade 1	18 5.1%	21 5.9%
Hyponatremia, Grade 2	1 0.3%	0 0%
Hyponatremia, Grade 3	0 0%	0 0%
Hyponatremia, Grade 4	0 0%	0 0%
LDL Cholesterol, Grades 1 to 4	41 11.5%	25 7%
LDL Cholesterol, Grades 2 to 4	14 3.9%	10 2.8%
LDL Cholesterol, Grades 3 to 4	5 1.4%	3 0.8%
LDL Cholesterol, Grade 1	27 7.6%	15 4.2%
LDL Cholesterol, Grade 2	9 2.5%	7 2%
LDL Cholesterol, Grade 3	5 1.4%	3 0.8%
LDL Cholesterol, Grade 4	0 0%	0 0%
Lactate Dehydrogenase, Grades 1 to 4	3 0.8%	4 1.1%
Lactate Dehydrogenase, Grades 2 to 4	0 0%	1 0.3%
Lactate Dehydrogenase, Grades 3 to 4	0 0%	0 0%
Lactate Dehydrogenase, Grade 1	3 0.8%	3 0.8%
Lactate Dehydrogenase, Grade 2	0 0%	1 0.3%
Lactate Dehydrogenase, Grade 3	0 0%	0 0%
Lactate Dehydrogenase, Grade 4	0 0%	0 0%
Lipase, Grades 1 to 4	41 11.5%	50 14%
Lipase, Grades 2 to 4	23 6.5%	25 7%
Lipase, Grades 3 to 4	5 1.4%	9 2.5%
Lipase, Grade 1	18 5.1%	25 7%
Lipase, Grade 2	18 5.1%	16 4.5%
Lipase, Grade 3	4 1.1%	4 1.1%
Lipase, Grade 4	1 0.3%	5 1.4%
Phosphate, Grades 1 to 4	40 11.2%	47 13.1%
Phosphate, Grades 2 to 4	19 5.3%	31 8.7%
Phosphate, Grades 3 to 4	1 0.3%	3 0.8%
Phosphate, Grade 1	21 5.9%	16 4.5%
Phosphate, Grade 2	18 5.1%	28 7.8%
Phosphate, Grade 3	1 0.3%	3 0.8%
Phosphate, Grade 4	0 0%	0 0%
Triglycerides, Grades 1 to 4	56 15.7%	44 12.3%
Triglycerides, Grades 2 to 4	11 3.1%	10 2.8%
Triglycerides, Grades 3 to 4	6 1.7%	3 0.8%
Triglycerides, Grade 1	45 12.6%	34 9.5%
Triglycerides, Grade 2	5 1.4%	7 2%
Triglycerides, Grade 3	5 1.4%	2 0.6%
Triglycerides, Grade 4	1 0.3%	1 0.3%

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. Data cut-off dates for analysis at Week 24 and Week 48 were 19-Jan-2018 and 22-May-2018 respectively. Number of participants who discontinued treatment due to AEs have been reported.
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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Up to Week 24	6 1.7%	4 1.1%
Up to Week 48	7 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 were collected to perform evaluation of renal inflammation biomarkers which included Serum Cystatin C and Serum Retinol Binding Protein (RBP). Baseline value is the latest pre-dose assessment. Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.
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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Serum Cystatin C, Week 24, n=338, 336	-0.05 (0.007)	-0.03 (0.007)
Serum Cystatin C, Week 48, n=324, 332	-0.07 (0.007)	-0.04 (0.006)
Serum RBP, Week 24, n=332, 334	1.6 (0.41)	1.9 (0.51)
Serum RBP, Week 48, n=322, 332	0.5 (0.47)	0.6 (0.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.025
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Serum Cystatin C, Week 24

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.05 to -0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Serum Cystatin C, Week 48

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.683
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.6 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Serum RBP, Week 24

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.930
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.4 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Serum RBP, Week 48

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 and/or urine were collected to perform evaluation of renal inflammation 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 post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.
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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
GFR-cystatin C adjusted, Week 24, n=338, 336	4.4 (0.63)	2.2 (0.60)
GFR-cystatin C adjusted, Week 48, n=324, 332	7.0 (0.60)	4.1 (0.59)
GFR-creatinine adjusted, Week 24, n=340, 341	-13.5 (0.59)	-16.7 (0.56)
GFR-creatinine adjusted, Week 48, n=326,335	-12.1 (0.56)	-15.6 (0.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 95%; 0.5 to 4.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	GFR-cystatin C adjusted, Week 24

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.8
	Confidence Interval	(2-Sided) 95%; 1.2 to 4.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	GFR-cystatin C adjusted, Week 48

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 95%; 1.6 to 4.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	GFR-creatinine adjusted, Week 24

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.5
	Confidence Interval	(2-Sided) 95%; 2.0 to 5.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	GFR- creatinine adjusted, Week 48

17. Secondary Outcome

Title	Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Weeks 24, 48
Description	Blood and/or urine were collected to perform evaluation of renal inflammation biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), presence of diabetes mellitus (factor), presence of hypertension (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.
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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Serum or Plasma Creatinine, Week 24, n=340, 343	11.88 (0.510)	15.07 (0.520)
Serum or Plasma Creatinine, Week 48, n=326, 335	10.39 (0.466)	13.61 (0.480)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.19
	Confidence Interval	(2-Sided) 95%; -4.62 to -1.75
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.22
	Confidence Interval	(2-Sided) 95%; -4.54 to -1.91
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48

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 which included Urine and Serum B2M, Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine. Baseline value is defined as the latest pre-dose assessment. Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Statistical analysis of changes from baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios. Estimated ratio of geometric means (each visit over Baseline) and 95% confidence interval (CI) have been presented.
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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Serum B2M, Week 24, n=338, 335	0.798	0.872
Serum B2M, Week 48, n=324, 332	0.806	0.892
Urine B2M, Week 24, n=121, 95	0.887	1.351
Urine B2M, Week 48, n=119, 103	0.900	1.338
Urine Albumin/Creatinine, Week 24, n=254, 252	1.014	1.050
Urine Albumin/Creatinine , Week 48, n=237, 244	0.934	1.048
Urine B2M/Urine Creatinine , Week 24, n=121, 95	0.852	1.331
Urine B2M/Urine Creatinine , Week 48, n=114, 100	0.888	1.278
Urine Phosphate, Week 24, n=330, 332	1.115	1.012
Urine Phosphate , Week 48, n=316, 330	1.061	1.075
Urine Protein/Creatinine , Week 24, n=269, 265	0.850	1.016
Urine Protein/Creatinine , Week 48, n=252, 269	0.879	1.061
Urine RBP 4, Week 24, n=332, 330	0.934	1.073
Urine RBP 4, Week 48, n=318, 328	1.115	1.490
Urine RBP 4/Urine Creatinine , Week 24, n=329, 330	0.919	1.110
Urine RBP 4/Urine Creatinine , Week 48, n=304, 318	1.147	1.500

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.915
	Confidence Interval	(2-Sided) 95%; 0.887 to 0.943
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Serum B2M

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.904
	Confidence Interval	(2-Sided) 95%; 0.880 to 0.929
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Serum B2M

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.656
	Confidence Interval	(2-Sided) 95%; 0.491 to 0.877
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Urine B2M

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.672
	Confidence Interval	(2-Sided) 95%; 0.551 to 0.821
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Urine B2M

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.575
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.965
	Confidence Interval	(2-Sided) 95%; 0.853 to 1.092
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Urine Albumin/Creatinine

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.051
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.891
	Confidence Interval	(2-Sided) 95%; 0.793 to 1.001
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Urine Albumin/Creatinine

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.640
	Confidence Interval	(2-Sided) 95%; 0.493 to 0.831
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Urine B2M/Urine Creatinine

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.695
	Confidence Interval	(2-Sided) 95%; 0.576 to 0.839
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Urine B2M/Urine Creatinine

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.099
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	1.102
	Confidence Interval	(2-Sided) 95%; 0.982 to 1.237
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Urine Phosphate

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.816
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.987
	Confidence Interval	(2-Sided) 95%; 0.886 to 1.100
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Urine Phosphate

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.836
	Confidence Interval	(2-Sided) 95%; 0.774 to 0.904
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Urine Protein/Creatinine

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.829
	Confidence Interval	(2-Sided) 95%; 0.773 to 0.888
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Urine Protein/Creatinine

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.087
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.871
	Confidence Interval	(2-Sided) 95%; 0.743 to 1.020
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Urine RBP 4

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.748
	Confidence Interval	(2-Sided) 95%; 0.644 to 0.870
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Urine RBP 4

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.828
	Confidence Interval	(2-Sided) 95%; 0.727 to 0.944
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Urine RBP 4/Urine Creatinine

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.765
	Confidence Interval	(2-Sided) 95%; 0.677 to 0.864
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Urine RBP 4/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. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.
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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Bone-ALP, Week 24, n=334, 332	0.91 (0.179)	3.13 (0.199)
Bone-ALP, Week 48, n=321, 331	1.21 (0.193)	3.79 (0.239)
Serum Osteocalcin, Week 24, n=335, 334	2.56 (0.341)	6.74 (0.347)
Serum Osteocalcin, Week 48, n=322, 330	0.78 (0.311)	6.01 (0.400)
PINP, Week 24, n=337, 336	4.5 (0.91)	18.3 (1.06)
PINP, Week 48, n=321, 334	0.5 (0.83)	13.1 (0.84)
CTX-1, Week 24, n=337, 334	0.1192 (0.01304)	0.2820 (0.01472)
CTX-1, Week 48, n=323, 331	0.1338 (0.01258)	0.3352 (0.01885)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.23
	Confidence Interval	(2-Sided) 95%; -2.75 to -1.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Bone ALP

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.58
	Confidence Interval	(2-Sided) 95%; -3.19 to -1.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Bone ALP

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.19
	Confidence Interval	(2-Sided) 95%; -5.15 to -3.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 28. Serum Osteocalcin

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5.23
	Confidence Interval	(2-Sided) 95%; -6.22 to -4.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Serum Osteocalcin

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-13.8
	Confidence Interval	(2-Sided) 95%; -16.5 to -11.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Serum PINP

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-12.6
	Confidence Interval	(2-Sided) 95%; -15.0 to -10.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Serum PINP

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1628
	Confidence Interval	(2-Sided) 95%; -0.2015 to -0.1241
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. CTX-1

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2015
	Confidence Interval	(2-Sided) 95%; -0.2460 to -0.1569
	Parameter Dispersion	Type: Value:
	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. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, baseline plasma HIV-1 RNA (factor), baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction; with visit as the repeated factor.
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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Serum Vitamin D, Week 24, n=337, 337	5.9 (1.15)	12.4 (1.33)
Serum Vitamin D, Week 48, n=322, 333	-3.1 (0.89)	3.1 (1.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-6.5
	Confidence Interval	(2-Sided) 95%; -9.9 to -3.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model Repeated Measures
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-6.2
	Confidence Interval	(2-Sided) 95%; -9.0 to -3.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48

21. Secondary Outcome

Title	Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48
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 (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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Serum or Plasma Cholesterol, Week 24, n=294, 297	9.4 (17.44)	-4.7 (16.12)
Serum or Plasma Cholesterol, Week 48, n=280, 289	10.5 (18.89)	-2.4 (17.14)
HDL Cholesterol, Direct, Week 24, n=294, 297	16.4 (22.58)	3.4 (21.55)
HDL Cholesterol, Direct, Week 48, n=280, 289	15.0 (25.07)	5.0 (33.04)
LDL Cholesterol, Week 24, n=294, 297	12.4 (45.05)	-8.1 (23.70)
LDL Cholesterol, Week 48, n=280, 289	14.8 (48.74)	-4.0 (24.06)
Triglycerides ,Week 24, n=294, 297	8.5 (46.57)	4.3 (72.35)
Triglycerides , Week 48, n=280, 289	12.8 (68.99)	4.4 (70.43)

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 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 (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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Total/HDL Cholesterol Ratio, Week 24, n=294, 297	-4.0 (19.08)	-4.6 (27.52)
Total/HDL Cholesterol Ratio, Week 48, n=280, 289	-0.2 (31.10)	-4.4 (16.96)

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). The higher the grade, the more severe the symptoms. Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Weeks 24 and 48 have been presented. Participants without any post-Baseline fasting LDL cholesterol value prior to Week 48 or those who had Baseline lipids-lowering agents are not included. Lipid Last Observation Carried Forward (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values.
Time Frame	Up to Week 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Week 24, n=309, 316	4 1.1%	2 0.6%
Week 48, n=318, 320	4 1.1%	3 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.157
	Comments	Fisher's exact p-value.
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -0.6 to 4.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.414
	Comments	Fisher's exact p-value.
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -1.7 to 4.2
	Parameter Dispersion	Type: Value:
	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, >200), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Baseline CD4+ cell count, <=200,n=31,29	90 25.3%	86 24%
Baseline CD4+ cell count, >200,n=325,329	93 26.1%	94 26.3%
Female, n=59, 52	93 26.1%	96 26.8%
Male, n=297, 306	92 25.8%	92 25.7%
Age, <35,n= 211, 205	93 26.1%	95 26.5%
Age, 35 to <50,n=116, 107	91 25.6%	93 26%
Age, >=50, n=29, 46	93 26.1%	85 23.7%
Baseline plasma HIV-1 RNA, <=100000,n=282,282	93 26.1%	95 26.5%
Baseline plasma HIV-1 RNA, >100000,n=74, 76	92 25.8%	87 24.3%
Race, White, n=243,248	93 26.1%	95 26.5%
Race, African American/African H., n=44, 36	93 26.1%	81 22.6%
Race, Asian, n=37, 42	89 25%	93 26%
Race, Other, n=32, 32	94 26.4%	94 26.3%

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, >200), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian, 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Baseline CD4+ cell count, <=200,n=31,29	81 22.8%	90 25.1%
Baseline CD4+ cell count, >200,n=325,329	91 25.6%	93 26%
Female, n=59, 52	88 24.7%	94 26.3%
Male, n=297, 306	90 25.3%	92 25.7%
Age, <35,n= 211, 205	92 25.8%	93 26%
Age, 35 to <50,n=116, 107	86 24.2%	94 26.3%
Age, >=50, n=29, 46	90 25.3%	87 24.3%
Baseline plasma HIV-1 RNA, <=100000,n=282,282	90 25.3%	93 26%
Baseline plasma HIV-1 RNA, >100000,n=74, 76	88 24.7%	91 25.4%
Race, White, n=243,248	90 25.3%	94 26.3%
Race, African American/African H., n=44, 36	89 25%	81 22.6%
Race, Asian, n=37, 42	92 25.8%	98 27.4%
Race, Other, n=32, 32	88 24.7%	94 26.3%

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 latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Baseline plasma HIV-1 RNA,<=100000, n=257,264	220.0 (11.72)	212.4 (11.56)
Baseline plasma HIV-1 RNA,>100000, n=67,70	238.5 (23.09)	235.5 (22.70)
Baseline CD4+ cell count,<=200, n=26, 27	200.5 (36.97)	177.9 (36.18)
Baseline CD4+ cell count,>200, n=298, 307	225.9 (10.84)	220.7 (10.68)
Age group-1, <35,n= 194, 192	233.6 (13.49)	225.2 (13.53)
Age group-1, 35 to <50, n=104, 101	208.7 (18.40)	211.2 (18.67)
Age group-1, >=50, n=26, 41	212.6 (36.84)	194.8 (29.27)
Female, n=54, 49	237.1 (25.53)	226.8 (26.98)
Male, n=270, 285	221.2 (11.41)	215.6 (11.11)
Race, White, n=223, 232	226.0 (12.58)	219.9 (12.37)
Race, African Am/African H., n=38, 31	209.4 (30.54)	232.5 (33.79)
Race, Asian, n=34, 41	246.4 (32.36)	197.2 (29.48)
Race, Other, n=29, 30	200.0 (34.91)	208.1 (34.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	7.6
	Confidence Interval	(2-Sided) 95%; -24.6 to 39.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Baseline plasma HIV-1 RNA,<=100000. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count and treatment and HIV-1 RNA interaction.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.0
	Confidence Interval	(2-Sided) 95%; -59.8 to 65.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Baseline plasma HIV-1 RNA,>100000. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count and treatment and HIV-1 RNA interaction.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	22.6
	Confidence Interval	(2-Sided) 95%; -78.3 to 123.5
	Parameter Dispersion	Type: Value:
	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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.2
	Confidence Interval	(2-Sided) 95%; -24.7 to 35.1
	Parameter Dispersion	Type: Value:
	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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	8.4
	Confidence Interval	(2-Sided) 95%; -29.1 to 45.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Age<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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -53.9 to 48.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Age 35 to <50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	17.7
	Confidence Interval	(2-Sided) 95%; -74.6 to 110.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Age>=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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	10.4
	Confidence Interval	(2-Sided) 95%; -62.3 to 83.1
	Parameter Dispersion	Type: Value:
	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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.6
	Confidence Interval	(2-Sided) 95%; -25.6 to 36.9
	Parameter Dispersion	Type: Value:
	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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	6.1
	Confidence Interval	(2-Sided) 95%; -28.5 to 40.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Race group white. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race group, and treatment and race group interaction.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-23.0
	Confidence Interval	(2-Sided) 95%; -112.6 to 66.6
	Parameter Dispersion	Type: Value:
	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 group, and treatment and race group interaction.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	49.2
	Confidence Interval	(2-Sided) 95%; -36.3 to 134.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Race group Asian. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race group, and treatment and race group interaction.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-8.1
	Confidence Interval	(2-Sided) 95%; -104.1 to 87.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Race group Other. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, race group, and treatment and race group interaction.

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 latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age, 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Baseline plasma HIV-1 RNA,<=100000, n=268,268	187.72 (10.860)	167.93 (10.842)
Baseline plasma HIV-1 RNA,>100000, n=72,73	206.63 (21.107)	205.96 (20.990)
Baseline CD4+ cell count,<=200, n=29,27	157.01 (33.113)	120.17 (34.151)
Baseline CD4+ cell count,>200, n=311, 314	195.11 (10.026)	180.73 (9.972)
Age, <35,n= 203,199	202.76 (12.456)	177.62 (12.563)
Age, 35 to <50, n=109, 100	172.05 (16.983)	179.87 (17.733)
Age, >=50, n=28, 42	188.79 (33.534)	159.34 (27.344)
Female, n=57,50	199.45 (23.498)	181.78 (25.263)
Male, n=283,291	190.21 (10.538)	175.05 (10.400)
Race, White, n=235,236	204.36 (11.561)	180.49 (11.559)
Race, African Am/African H., n=41,33	147.04 (27.706)	180.96 (30.880)
Race, Asian, n=34, 41	169.92 (30.502)	165.46 (27.793)
Race, Other, n=30,31	179.13 (32.374)	150.64 (31.914)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	19.80
	Confidence Interval	(2-Sided) 95%; -10.23 to 49.83
	Parameter Dispersion	Type: Value:
	Estimation Comments	Baseline plasma HIV-1 RNA,<=100000. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and HIV-1 RNA interaction.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; -57.07 to 58.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	Baseline plasma HIV-1 RNA,>100000. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, and treatment and HIV-1 RNA interaction.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	36.84
	Confidence Interval	(2-Sided) 95%; -55.94 to 129.63
	Parameter Dispersion	Type: Value:
	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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	14.37
	Confidence Interval	(2-Sided) 95%; -13.38 to 42.12
	Parameter Dispersion	Type: Value:
	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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	25.14
	Confidence Interval	(2-Sided) 95%; -9.56 to 59.85
	Parameter Dispersion	Type: Value:
	Estimation Comments	Age<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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-7.82
	Confidence Interval	(2-Sided) 95%; -55.98 to 40.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	Age 35 to <50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	29.45
	Confidence Interval	(2-Sided) 95%; -55.47 to 114.38
	Parameter Dispersion	Type: Value:
	Estimation Comments	Age>=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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	17.67
	Confidence Interval	(2-Sided) 95%; -49.89 to 85.23
	Parameter Dispersion	Type: Value:
	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
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	15.16
	Confidence Interval	(2-Sided) 95%; -13.90 to 44.21
	Parameter Dispersion	Type: Value:
	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.

28. Secondary Outcome

Title	Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Utility Score at Weeks 4, 24, 48
Description	EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has 1 question assessing each of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. The health state is defined by combining the levels of answers from each of the 5 questions. Each health state is referred to in terms of a 5 digit code. Health state 5 digit code is translated into utility score, which is valued up to 1 (perfect health) with lower values meaning worse state. EQ-5D-5L utility score ranges from -0.281 to 1. Higher scores indicate better health. Baseline was the latest pre-dose assessment and change from Baseline=post-dose value minus Baseline value.
Time Frame	Baseline and Weeks 4, 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Week 4, n=349, 348	0.0130 (0.00362)	0.0078 (0.00353)
Week 24, n=352, 351	0.0131 (0.00371)	0.0168 (0.00333)
Week 48, n=352, 351	0.0134 (0.00384)	0.0129 (0.00349)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.302
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0052
	Confidence Interval	(2-Sided) 95%; -0.0047 to 0.0152
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 4. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit with visit as the repeated factor

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.450
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.0038
	Confidence Interval	(2-Sided) 95%; -0.0136 to 0.0060
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week24. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit with visit as the repeated factor

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.934
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0004
	Confidence Interval	(2-Sided) 95%; -0.0098 to 0.0106
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week48. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), and Baseline EQ-5D utility, treatment*visit and Baseline EQ-5D utility*visit with visit as the repeated factor

29. Secondary Outcome

Title	Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24 48
Description	EQ-5D-5L questionnaire provides a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). MMRM was run on the LOCF dataset, using the observed margins (OM) option. Baseline was the latest pre-dose assessment value and change from Baseline=post-dose value minus Baseline value.
Time Frame	Baseline (Day 1) and Weeks 4, 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 dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.	Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
Measure Participants	356	358
Week 4, n=349, 348	2.3 (0.48)	1.2 (0.52)
Week 24, n=352, 350	3.7 (0.54)	3.2 (0.51)
Week 48, n=352, 350	4.3 (0.49)	2.8 (0.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.137
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.1
	Confidence Interval	(2-Sided) 95%; -0.3 to 2.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 4. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA (factor),Baseline CD4+ cell count (factor), Baseline EQ-5D thermometer, treatment*visit and Baseline EQ-5D thermometer*visit with visit as the repeated factor

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.458
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -0.9 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week24. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA (factor),Baseline CD4+ cell count (factor), Baseline EQ-5D thermometer, treatment*visit and Baseline EQ-5D thermometer*visit with visit as the repeated factor

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.031
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; 0.1 to 2.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week48. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA (factor),Baseline CD4+ cell count (factor), Baseline EQ-5D thermometer, treatment*visit and Baseline EQ-5D thermometer*visit with visit as the repeated factor

Adverse Events

Time Frame	Post-Baseline serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment up to Week 48 (data cut-off for primary analysis).
Adverse Event Reporting Description	Post-Baseline SAEs and non-serious AEs were reported for the Safety Population.
Arm/Group Title	DTG + 3TC		DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of dolutegravir plus lamivudine (DTG + 3TC) once daily for 48 weeks.		Participants received a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (DTG + TDF/FTC) fixed dose combination (FDC) once daily for 48 weeks.
All Cause Mortality
	DTG + 3TC		DTG + TDF/FTC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/356 (0%)		0/358 (0%)
Serious Adverse Events
	DTG + 3TC		DTG + TDF/FTC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/356 (5.9%)		22/358 (6.1%)
Blood and lymphatic system disorders
Lymphadenopathy	0/356 (0%)	0	1/358 (0.3%)	1
Cardiac disorders
Coronary artery stenosis	1/356 (0.3%)	1	0/358 (0%)	0
Gastrointestinal disorders
Gastric ulcer haemorrhage	1/356 (0.3%)	1	0/358 (0%)	0
Intestinal obstruction	0/356 (0%)	0	1/358 (0.3%)	1
General disorders
Non-cardiac chest pain	0/356 (0%)	0	1/358 (0.3%)	1
Hepatobiliary disorders
Cholecystitis acute	0/356 (0%)	0	1/358 (0.3%)	1
Cholelithiasis	0/356 (0%)	0	1/358 (0.3%)	1
Hepatitis toxic	1/356 (0.3%)	1	0/358 (0%)	0
Infections and infestations
Hepatitis A	3/356 (0.8%)	3	4/358 (1.1%)	4
Appendicitis	1/356 (0.3%)	1	1/358 (0.3%)	1
Pneumonia	1/356 (0.3%)	1	1/358 (0.3%)	1
Abscess limb	1/356 (0.3%)	1	0/358 (0%)	0
Acute hepatitis C	1/356 (0.3%)	1	0/358 (0%)	0
Anal abscess	0/356 (0%)	0	1/358 (0.3%)	1
Bacterial infection	1/356 (0.3%)	1	0/358 (0%)	0
Cellulitis	0/356 (0%)	0	1/358 (0.3%)	1
Chagoma	1/356 (0.3%)	1	0/358 (0%)	0
Gastroenteritis	0/356 (0%)	0	1/358 (0.3%)	1
Helicobacter gastritis	1/356 (0.3%)	1	0/358 (0%)	0
Herpes zoster	0/356 (0%)	0	1/358 (0.3%)	1
Lower respiratory tract infection	1/356 (0.3%)	1	0/358 (0%)	0
Perineal abscess	1/356 (0.3%)	1	0/358 (0%)	0
Injury, poisoning and procedural complications
Head injury	1/356 (0.3%)	1	1/358 (0.3%)	1
Joint dislocation	1/356 (0.3%)	1	0/358 (0%)	0
Post lumbar puncture syndrome	1/356 (0.3%)	1	0/358 (0%)	0
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/356 (0%)	0	1/358 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts	1/356 (0.3%)	1	0/358 (0%)	0
B-cell lymphoma	0/356 (0%)	0	1/358 (0.3%)	1
Clear cell renal cell carcinoma	0/356 (0%)	0	1/358 (0.3%)	1
Nervous system disorders
Polyneuropathy	0/356 (0%)	0	1/358 (0.3%)	1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/356 (0%)	0	1/358 (0.3%)	1
Psychiatric disorders
Major depression	1/356 (0.3%)	1	0/358 (0%)	0
Psychotic disorder	1/356 (0.3%)	1	0/358 (0%)	0
Substance-induced psychotic disorder	1/356 (0.3%)	1	0/358 (0%)	0
Suicide attempt	1/356 (0.3%)	1	0/358 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/356 (0%)	0	1/358 (0.3%)	1
Other (Not Including Serious) Adverse Events
	DTG + 3TC		DTG + TDF/FTC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	215/356 (60.4%)		226/358 (63.1%)
Gastrointestinal disorders
Diarrhoea	33/356 (9.3%)	42	42/358 (11.7%)	55
Nausea	12/356 (3.4%)	12	30/358 (8.4%)	33
Abdominal pain	11/356 (3.1%)	11	9/358 (2.5%)	10
Dyspepsia	7/356 (2%)	10	8/358 (2.2%)	8
Haemorrhoids	8/356 (2.2%)	8	7/358 (2%)	7
Abdominal pain upper	4/356 (1.1%)	6	8/358 (2.2%)	10
Vomiting	8/356 (2.2%)	9	4/358 (1.1%)	5
General disorders
Pyrexia	15/356 (4.2%)	19	11/358 (3.1%)	12
Fatigue	13/356 (3.7%)	15	12/358 (3.4%)	13
Influenza like illness	11/356 (3.1%)	11	12/358 (3.4%)	18
Infections and infestations
Nasopharyngitis	33/356 (9.3%)	45	37/358 (10.3%)	50
Upper respiratory tract infection	24/356 (6.7%)	26	22/358 (6.1%)	27
Pharyngitis	23/356 (6.5%)	25	13/358 (3.6%)	18
Syphilis	17/356 (4.8%)	18	15/358 (4.2%)	15
Bronchitis	20/356 (5.6%)	21	11/358 (3.1%)	12
Influenza	14/356 (3.9%)	16	11/358 (3.1%)	13
Sinusitis	12/356 (3.4%)	14	9/358 (2.5%)	10
Gastroenteritis	10/356 (2.8%)	10	10/358 (2.8%)	10
Gonorrhoea	9/356 (2.5%)	12	10/358 (2.8%)	13
Tonsillitis	10/356 (2.8%)	11	8/358 (2.2%)	8
Herpes zoster	4/356 (1.1%)	4	12/358 (3.4%)	12
Pharyngotonsillitis	6/356 (1.7%)	6	8/358 (2.2%)	11
Respiratory tract infection	5/356 (1.4%)	8	9/358 (2.5%)	12
Respiratory tract infection viral	5/356 (1.4%)	6	8/358 (2.2%)	9
Metabolism and nutrition disorders
Vitamin D deficiency	9/356 (2.5%)	9	4/358 (1.1%)	4
Musculoskeletal and connective tissue disorders
Back pain	19/356 (5.3%)	25	19/358 (5.3%)	20
Arthralgia	5/356 (1.4%)	6	11/358 (3.1%)	12
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts	8/356 (2.2%)	8	11/358 (3.1%)	11
Nervous system disorders
Headache	40/356 (11.2%)	58	44/358 (12.3%)	73
Dizziness	8/356 (2.2%)	10	9/358 (2.5%)	9
Psychiatric disorders
Insomnia	16/356 (4.5%)	17	29/358 (8.1%)	32
Depression	9/356 (2.5%)	9	10/358 (2.8%)	10
Anxiety	8/356 (2.2%)	8	6/358 (1.7%)	7
Respiratory, thoracic and mediastinal disorders
Cough	7/356 (2%)	7	14/358 (3.9%)	14
Oropharyngeal pain	7/356 (2%)	7	12/358 (3.4%)	12
Rhinitis allergic	9/356 (2.5%)	14	3/358 (0.8%)	3
Vascular disorders
Hypertension	9/356 (2.5%)	10	7/358 (2%)	7

Limitations/Caveats

[Not Specified]

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