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

Sponsor

ViiV Healthcare (Industry)

Overall Status

Completed

CT.gov ID

NCT02831764

Collaborator

GlaxoSmithKline (Industry)

722

Enrollment

105

Locations

Arms

71.4

Actual Duration (Months)

6.9

Patients Per Site

0.1

Patients Per Site Per Month

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 disoproxil fumarate [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 + 3TC regimen to that of DTG + 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 :

722 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 HIV-1-infected Treatment-naïve Adults

Actual Study Start Date :

Jul 18, 2016

Actual Primary Completion Date :

Apr 4, 2018

Actual Study Completion Date :

Jun 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.

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)

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

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 received at least one dose of study treatment.

Secondary Outcome Measures

Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Weeks 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 CMH weights.
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 first Quartile and third Quartile have been presented.
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+ cells. Analysis was performed by flow cytometry.
Changes From Baseline in CD4+ Cell Counts at Week 24 and 48 [Baseline 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+ cells. Analysis was performed by flow cytometry. Baseline value is defined as the the latest pre-dose assessment. Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted least mean and standard error has been presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for the following covariates/factors: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, treatment and visit interaction, and Baseline CD4+ cell count and visit interaction, with visit as the repeated factor.
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 progressions summarize participants who had HIV infection stage 3 associated conditions or death. Indicators of clinical disease progression were defined as: CDC Category Stage 1 at enrollment to Stage 3 event; CDC Category Stage 2 at enrolment to Stage 3 event; CDC Category Stage 3 at enrollment to New Stage 3 Event; CDC Category Stage 1, 2 or 3 at enrolment to Death.
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 genotypic resistance to Integrase strand transfer inhibitor (INSTI) and/or Nucleoside reverse transcriptase inhibitor (NRTI) was summarized. The Viral Genotypic Population comprised of all participants in the ITT-E population who have available on-treatment genotypic resistance data.
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 were interpreted through a proprietary algorithm (from Monogram Biosciences) and provides the overall susceptibility of the drugs (Abacavir [ABC], elvitegravir [EGV], raltegravir [RAL], zidovudine [AZT], stavudine [D4T], didanosine [DDI]), emtricitabine [FTC], tenofovir disiproxil fumarate [TDF]). Partially sensitive and resistant cells were considered resistant in this analysis. Number of participants with phenotype at time of CVW by phenotypic cut-off at or prior to Week 48 have been presented. The Viral Phenotypic Population comprised of all participants in the ITT-E population who have available on-treatment phenotypic resistance data. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
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. Analyses presented herein used a data cut-off date of 22 May 2018 (for Week 48 database freeze), i.e. may include data collected after a participant's Week 48 visit.
Number of Participants With AEs by Maximum 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. AEs were evaluated by the investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented. Analyses presented herein used a data cut-off date of 22 May 2018 (for Week 48 database freeze), i.e. may include data collected after a participant's Week 48 visit.
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. AEs were evaluated by the investigator and graded according to the DAIDS toxicity scales from Grade 1 to 5. (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with drug related AEs and drug related AEs by by maximum grade have been presented. Analyses presented herein used a data cut-off date of 22 May 2018 (for Week 48 database freeze), i.e. may include data collected after a participant's Week 48 visit.
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 platelet count, neutrophils, hemoglobin, and Leukocytes. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Only those participants with maximum post-Baseline emergent hematology toxicities in any of the listed hematology parameters have been presented.
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), Albumin, Alkaline Phosphatase (ALP), Bilirubin, Carbon dioxide (CO2), Cholesterol, Creatine kinase (CPK), Creatinine, Direct Bilirubin, Glomerular filtration rate (GFR), Hypercalcemia, Hyperglycemia, Hyperkalemia, Hypernatremia, Hypocalcemia, Hypoglycemia, Hypokalemia and Hyponatremia, Low density lipid (LDL) Cholesterol, Lactate Dehydrogenase, Lipase and Phosphate. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Only those participants with maximum post-Baseline emergent chemistry toxicities in any of the chemistry parameters have been presented.
Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48 [Weeks 24 and 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. Number of participants who discontinued treatment due to AEs have been reported. Analyses presented herein used a data cut-off date of 19 January 2018 and 22 May 2018, respectively, for the Week 24 database freeze and Week 48 database freeze), i.e. may include data collected after a participant's Week 24 or 48 visit, respectively.
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 samples were collected to perform evaluation of renal biomarkers which included Serum Cystatin C and Serum RBP. Baseline value is the latest pre-dose assessment. Change from Baseline was defined as value at indicated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor.
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 samples were collected to perform evaluation of renal biomarkers which included Serum GFR from cystatin C adjusted using CKD-EPI (GFR-cystatin C adjusted) and Serum or Plasma GFR from creatinine adjusted using CKD-EPI. Baseline value is the latest pre-dose Assessment. Change from Baseline was defined as value at the indicated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor.
Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Weeks 24, 48 [Baseline and at Weeks 24, 48]
Blood and samples were collected to perform evaluation of renal biomarker which included Serum or Plasma Creatinine. Baseline value is defined as the the latest pre-dose assessment. Change from Baseline was calculated as value at the inidcated time point minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
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 Weeks 24, 48]
Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers: Urine and Serum B2M, Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine. Baseline value was the latest pre-dose assessment. Change from Baseline was performed on log-transformed data. Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Geometric mean ratio and 95% CI of geometric mean ratio have been presented. Biomarkers were Adjusted for treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, loge transformed Baseline biomarker value, treatment and visit interaction, and loge transformed Baseline biomarker value and visit interaction; with visit as the repeated factor.
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 (Day 1) 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. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as value at the indicated time point minus Baseline value.
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. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as value at the indicated time point minus Baseline value.
Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma High Density Lipoprotein (HDL) Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48 [Baseline 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).
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 the latest pre-dose assessment (Day 1). Percentage change from Baseline was calculated as 100 multiplied by ([post-dose visit value minus Baseline value] divided by Baseline value). Lipid last observation carried forwardd (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values. Participants on lipid-lowering agents at Baseline were excluded.
Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Weeks 24, 48 [Weeks 24 and 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). Percentage of participants with Grade 2 or greater laboratory abnormalities in fasting LDL cholesterol by Weeks 24 and 48 have been presented. Participants without any post-Baseline fasting LDL cholesterol value prior to Week 48 or those who had Baseline lipids-lowering agents were not included. Lipid Last Observation Carried Forward (LOCF) data was used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values.
Percentage 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 cells/mm^3, >200 cells/mm^3 for group-1), Baseline HIV-1 RNA (<=100000, >100000 c/mL) and Race (White, African American/African heritage, Asian other).
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 cells/mm^3, >200 cells/mm^3 for group-1), Baseline HIV-1 RNA (<=100000, >100000) and Race (White, African American/African H., Asian and other).
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 the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the inidicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from Analysis of Covariance (ANCOVA) model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only.
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 the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only.
Change From Baseline in European Quality of Life [EuroQoL] - 5 Dimensions - 5 Levels (EQ-5D-5L) Utility Score 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 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. MMRM was run on LOCF dataset. Baseline was the latest pre-dose assessment and change from Baseline=post-dose value minus Baseline value. Only those participants available at the specified time points were analyzed.
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 provided a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). MMRM was run on the LOCF dataset, using the observed margins (OM) option. Baseline was the latest pre-dose assessment value and change from Baseline=post-dose value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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	Birmingham	Alabama	United States	35294-3300
2	GSK Investigational Site	Los Angeles	California	United States	90069
3	GSK Investigational Site	Sacramento	California	United States	95825
4	GSK Investigational Site	San Francisco	California	United States	94109
5	GSK Investigational Site	San Leandro	California	United States	94577
6	GSK Investigational Site	Aurora	Colorado	United States	80045
7	GSK Investigational Site	Washington	District of Columbia	United States	20005
8	GSK Investigational Site	Fort Pierce	Florida	United States	34982
9	GSK Investigational Site	Miami	Florida	United States	33133
10	GSK Investigational Site	Miami	Florida	United States	33136
11	GSK Investigational Site	Orlando	Florida	United States	32803
12	GSK Investigational Site	West Palm Beach	Florida	United States	33407
13	GSK Investigational Site	Decatur	Georgia	United States	30033
14	GSK Investigational Site	Savannah	Georgia	United States	31401
15	GSK Investigational Site	Chicago	Illinois	United States	60612
16	GSK Investigational Site	Berkley	Michigan	United States	48072
17	GSK Investigational Site	Saint Louis	Missouri	United States	63139
18	GSK Investigational Site	Hillsborough	New Jersey	United States	08844
19	GSK Investigational Site	Newark	New Jersey	United States	07102
20	GSK Investigational Site	Cincinnati	Ohio	United States	45267-0405
21	GSK Investigational Site	Austin	Texas	United States	78705
22	GSK Investigational Site	Dallas	Texas	United States	75246
23	GSK Investigational Site	Fort Worth	Texas	United States	76104
24	GSK Investigational Site	Houston	Texas	United States	77009
25	GSK Investigational Site	Houston	Texas	United States	77098
26	GSK Investigational Site	Rosario	Santa Fe	Argentina	S2000PBJ
27	GSK Investigational Site	Buenos Aires		Argentina	C1221ADC
28	GSK Investigational Site	Buenos Aires		Argentina	C1425 AWK
29	GSK Investigational Site	Ciudad Autónoma de Buenos Aires		Argentina	C1426ABP
30	GSK Investigational Site	Cordoba		Argentina	5000
31	GSK Investigational Site	Darlinghurst	New South Wales	Australia	2010
32	GSK Investigational Site	Parramatta	New South Wales	Australia	2150
33	GSK Investigational Site	Melbourne	Victoria	Australia	Prahran 3181
34	GSK Investigational Site	North Fitzroy	Victoria	Australia	3068
35	GSK Investigational Site	Prahran	Victoria	Australia	3181
36	GSK Investigational Site	Bruxelles		Belgium	1090
37	GSK Investigational Site	Gent		Belgium	9000
38	GSK Investigational Site	Lodelinsart		Belgium	6042
39	GSK Investigational Site	Vancouver	British Columbia	Canada	V6Z 2C7
40	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2N2
41	GSK Investigational Site	Montreal	Quebec	Canada	H4A 3J1
42	GSK Investigational Site	Bobigny		France	93009
43	GSK Investigational Site	Lyon		France	69317
44	GSK Investigational Site	Paris Cedex 20		France	75970
45	GSK Investigational Site	Bonn	Nordrhein-Westfalen	Germany	53127
46	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	50937
47	GSK Investigational Site	Frankfurt/main		Germany	60590
48	GSK Investigational Site	Hamburg		Germany	20099
49	GSK Investigational Site	München		Germany	81675
50	GSK Investigational Site	Modena	Emilia-Romagna	Italy	41100
51	GSK Investigational Site	Genova	Liguria	Italy	16128
52	GSK Investigational Site	Milano	Lombardia	Italy	20142
53	GSK Investigational Site	Milano	Lombardia	Italy	20157
54	GSK Investigational Site	Torino	Piemonte	Italy	10149
55	GSK Investigational Site	Bergamo		Italy	24128
56	GSK Investigational Site	Milano		Italy	20162
57	GSK Investigational Site	Monza		Italy	20900
58	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44280
59	GSK Investigational Site	Distrito Federal		Mexico	03720
60	GSK Investigational Site	Mexico		Mexico	14000
61	GSK Investigational Site	Lima		Peru	1
62	GSK Investigational Site	Lima		Peru	Callao 2
63	GSK Investigational Site	Lima		Peru	Lima 13
64	GSK Investigational Site	Bydgoszcz		Poland	85-030
65	GSK Investigational Site	Amadora		Portugal	2720-276
66	GSK Investigational Site	Lisboa		Portugal	1349-019
67	GSK Investigational Site	Porto		Portugal	4200-319
68	GSK Investigational Site	Bucharest		Romania	021105
69	GSK Investigational Site	Bucuresti		Romania	30303
70	GSK Investigational Site	Iasi		Romania	700116
71	GSK Investigational Site	Izhevsk		Russian Federation	426067
72	GSK Investigational Site	Kazan		Russian Federation	420061
73	GSK Investigational Site	Kemerovo		Russian Federation	650056
74	GSK Investigational Site	Krasnodar		Russian Federation	350015
75	GSK Investigational Site	St. Petersburg		Russian Federation	193167
76	GSK Investigational Site	St.Peterburg		Russian Federation	190103
77	GSK Investigational Site	Alcorcon		Spain	28922
78	GSK Investigational Site	Barcelona		Spain	08003
79	GSK Investigational Site	Barcelona		Spain	08035
80	GSK Investigational Site	Barcelona		Spain	08036
81	GSK Investigational Site	Granada		Spain	18014
82	GSK Investigational Site	Madrid		Spain	28006
83	GSK Investigational Site	Madrid		Spain	28041
84	GSK Investigational Site	Madrid		Spain	28046
85	GSK Investigational Site	Malaga		Spain	29010
86	GSK Investigational Site	Marid		Spain	28040
87	GSK Investigational Site	Sevilla		Spain	41013
88	GSK Investigational Site	Valencia		Spain	46010
89	GSK Investigational Site	Valencia		Spain	46026
90	GSK Investigational Site	Bern		Switzerland	3010
91	GSK Investigational Site	Geneve		Switzerland	CH-1205
92	GSK Investigational Site	Zuerich		Switzerland	8091
93	GSK Investigational Site	Kaohsiung		Taiwan	807
94	GSK Investigational Site	Kaohsiung		Taiwan	813
95	GSK Investigational Site	New Taipei		Taiwan	220
96	GSK Investigational Site	Tainan		Taiwan	704
97	GSK Investigational Site	Taipei		Taiwan	11490
98	GSK Investigational Site	Taoyuan		Taiwan	330
99	GSK Investigational Site	Woolwich, London	London	United Kingdom	SE18 4QH
100	GSK Investigational Site	Brighton		United Kingdom	BN2 5BE
101	GSK Investigational Site	Liverpool		United Kingdom	L69 3GE
102	GSK Investigational Site	London		United Kingdom	E1 1BB
103	GSK Investigational Site	London		United Kingdom	NW3 2QG
104	GSK Investigational Site	London		United Kingdom	SE13 6LR
105	GSK Investigational Site	Manchester		United Kingdom	M13 0FH

Sponsors and Collaborators

ViiV Healthcare
GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, ViiV Healthcare

Study Documents (Full-Text)

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:

NCT02831764

Other Study ID Numbers:

205543
2016-000459-28

First Posted:

Jul 13, 2016

Last Update Posted:

Aug 11, 2022

Last Verified:

Jul 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by ViiV Healthcare

Additional relevant MeSH terms:

Infections

Communicable Diseases

HIV Infections

Acquired Immunodeficiency Syndrome

Study Results

Participant Flow

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

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC fixed dose combination (FDC) administered orally, once daily for 48 weeks.
Period Title: Overall Study
STARTED	360	359
COMPLETED	0	0
NOT COMPLETED	360	359

Baseline Characteristics

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC	Total
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.	Total of all reporting groups
Overall Participants	360	359	719
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	34.6 (10.72)	34.4 (10.35)	34.5 (10.53)
Sex: Female, Male (Count of Participants)
Female	54 15%	46 12.8%	100 13.9%
Male	306 85%	313 87.2%	619 86.1%
Race/Ethnicity, Customized (Count of Participants)
American (Am) Indian or Alaska (Al.) native	21 5.8%	24 6.7%	45 6.3%
Asian-Central/South Asian heritage (H.)	0 0%	3 0.8%	3 0.4%
Asian - East Asian H.	28 7.8%	26 7.2%	54 7.5%
Asian - South East Asian H.	6 1.7%	1 0.3%	7 1%
Black or African Am	55 15.3%	40 11.1%	95 13.2%
Native Hawaiian or other Pacific Islander	0 0%	5 1.4%	5 0.7%
White (Wt)-Arabic/North African H.	3 0.8%	3 0.8%	6 0.8%
Wt-Wt/Caucasian (Ca.)/European (Eu.) H.	234 65%	246 68.5%	480 66.8%
Am Indian or Al. native and Wt	12 3.3%	10 2.8%	22 3.1%
Black or African Am and Wt	1 0.3%	1 0.3%	2 0.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL (c/mL) at Week 48
Description	Percentage of participants with HIV-1 RNA<50 c/mL was obtained using Food and Drug Administration (FDA) Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest. This endpoint was analyzed using a stratified analysis with Cochran-Mantel-Haenszel (CMH) weights. Intent-To-Treat Exposed (ITT-E) Population was used which comprised of all randomized participants who received at least one dose of study treatment.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description
ITT-E Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Number (95% Confidence Interval) [Percentage of participants]	93 25.8%	94 26.2%

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 was greater than -10%.

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Adjusted difference in proportion
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95% -4.3 to 2.9
	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 copies per milliliter) and CD4+ cell count (<= vs. >200 cells per cubic millimeter [cells/mm^3]).

2. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Weeks 24
Description	Percentage of participants with HIV-1 RNA<50 c/mL was obtained using FDA Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant ART prior to the visit of interest. This endpoint was analyzed using a stratified analysis with CMH weights.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description
ITT-E Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Number (95% Confidence Interval) [Percentage of participants]	94 26.1%	94 26.2%

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 was greater than -10%.

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Adjusted difference in proportion
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95% -3.4 to 3.6
	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/mm^3).

3. Secondary Outcome

Title	Time to Viral Suppression (HIV-1 RNA <50 c/mL)
Description	Time of viral suppression is defined as the first viral load value <50 c/mL. Nonparametric Kaplan-Meier method was performed. Participants who withdrew for any reason without being suppressed were censored at date of withdrawal. Participants who have not been withdrawn and have not had viral suppression at time of the analysis were censored at last viral load date. Confidence Interval (CI) was estimated using the Brookmeyer-Crowley method. Median along with first Quartile and third Quartile have been presented.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description
ITT-E Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
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	0.825
	Comments	The generalised Wilcoxon procedure was used to estimate a p-value for detecting a difference in cumulative incidence curves between treatment groups.
	Method	Generalised Wilcoxon procedure
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95% 0.88 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratios were estimated using the Cox proportional hazard regression model.

4. Secondary Outcome

Title	CD4+ Cell Counts at Weeks 24 and 48
Description	CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+ cells. Analysis was performed by flow cytometry.
Time Frame	Weeks 24 and 48

Outcome Measure Data

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

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Week 24, n=349,345	650.4 (257.02)	633.0 (287.37)
Week 48, n=337,340	688.1 (266.39)	689.8 (308.49)

5. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Week 24, n=349, 345	188.8 (8.77)	163.2 (9.08)
Week 48, n=337, 340	225.7 (8.94)	217.2 (9.93)

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	0.043
	Comments
	Method	Mixed Model Repeated Measures (MMRM)
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	25.6
	Confidence Interval	(2-Sided) 95% 0.8 to 50.4
	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	0.523
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	8.5
	Confidence Interval	(2-Sided) 95% -17.7 to 34.8
	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 progressions summarize participants who had HIV infection stage 3 associated conditions or death. Indicators of clinical disease progression were defined as: CDC Category Stage 1 at enrollment to Stage 3 event; CDC Category Stage 2 at enrolment to Stage 3 event; CDC Category Stage 3 at enrollment to New Stage 3 Event; CDC Category Stage 1, 2 or 3 at enrolment to Death.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description
ITT-E Population

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

7. Secondary Outcome

Title	Number of Participants With Treatment-emergent Genotypic Resistance
Description	Number of participants, who meet confirmed virologic withdrawal (CVW) criteria, with treatment emergent genotypic resistance to Integrase strand transfer inhibitor (INSTI) and/or Nucleoside reverse transcriptase inhibitor (NRTI) was summarized. The Viral Genotypic Population comprised of all participants in the ITT-E population who have available on-treatment genotypic resistance data.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description
Viral Genotypic Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	2	2
INSTI Mutations	0 0%	0 0%
Major mutations of the 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 were interpreted through a proprietary algorithm (from Monogram Biosciences) and provides the overall susceptibility of the drugs (Abacavir [ABC], elvitegravir [EGV], raltegravir [RAL], zidovudine [AZT], stavudine [D4T], didanosine [DDI]), emtricitabine [FTC], tenofovir disiproxil fumarate [TDF]). Partially sensitive and resistant cells were considered resistant in this analysis. Number of participants with phenotype at time of CVW by phenotypic cut-off at or prior to Week 48 have been presented. The Viral Phenotypic Population comprised of all participants in the ITT-E population who have available on-treatment phenotypic resistance data. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description
Viral Phenotypic Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	2	2
INSTI, DTG, Sensitive, n=2,1	2 0.6%	1 0.3%
INSTI, DTG, Resistant, n=2,1	0 0%	0 0%
INSTI, EGV, Sensitive, n=2,1	2 0.6%	1 0.3%
INSTI, EGV, Resistant, n=2,1	0 0%	0 0%
INSTI, RAL, Sensitive, n=2,1	2 0.6%	1 0.3%
INSTI, RAL, Resistant, n=2,1	0 0%	0 0%
NRTI, 3TC, Sensitive, n=2,2	2 0.6%	2 0.6%
NRTI, 3TC, Resistant, n=2,2	0 0%	0 0%
NRTI, ABC, Sensitive, n=2,2	2 0.6%	2 0.6%
NRTI, ABC, Resistant, n=2,2	0 0%	0 0%
NRTI, AZT, Sensitive, n=2,2	2 0.6%	2 0.6%
NRTI, AZT, Resistant, n=2,2	0 0%	0 0%
NRTI, D4T, Sensitive, n=2,2	2 0.6%	2 0.6%
NRTI, D4T, Resistant, n=2,2	0 0%	0 0%
NRTI, DDI, Sensitive, n=2,2	2 0.6%	2 0.6%
NRTI, DDI, Resistant, n=2,2	0 0%	0 0%
NRTI, FTC, Sensitive, n=2,2	2 0.6%	2 0.6%
NRTI, FTC, Resistant, n=2,2	0 0%	0 0%
NRTI, TDF, Sensitive, n=2,2	2 0.6%	2 0.6%
NRTI, TDF, Resistant, n=2,2	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. Analyses presented herein used a data cut-off date of 22 May 2018 (for Week 48 database freeze), i.e. may include data collected after a participant's Week 48 visit.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description
Safety Population

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

10. Secondary Outcome

Title	Number of Participants With AEs by Maximum Severity Grades
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs were evaluated by the investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with adverse events by maximum grade have been presented. Analyses presented herein used a data cut-off date of 22 May 2018 (for Week 48 database freeze), i.e. may include data collected after a participant's Week 48 visit.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description
Safety Population

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

11. Secondary Outcome

Title	Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs were evaluated by the investigator and graded according to the DAIDS toxicity scales from Grade 1 to 5. (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms. Number of participants with drug related AEs and drug related AEs by by maximum grade have been presented. Analyses presented herein used a data cut-off date of 22 May 2018 (for Week 48 database freeze), i.e. may include data collected after a participant's Week 48 visit.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description
Safety Population

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

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Hemoglobin, Grades 1 to 4	8 2.2%	7 1.9%
Hemoglobin, Grades 2 to 4	5 1.4%	4 1.1%
Hemoglobin, Grades 3 to 4	2 0.6%	1 0.3%
Hemoglobin, Grade 1	3 0.8%	3 0.8%
Hemoglobin, Grade 2	3 0.8%	3 0.8%
Hemoglobin, Grade 3	1 0.3%	1 0.3%
Hemoglobin, Grade 4	1 0.3%	0 0%
Leukocytes, Grades 1 to 4	4 1.1%	3 0.8%
Leukocytes, Grades 2 to 4	1 0.3%	0 0%
Leukocytes, Grades 3 to 4	0 0%	0 0%
Leukocytes, Grade 1	3 0.8%	3 0.8%
Leukocytes, Grade 2	1 0.3%	0 0%
Leukocytes, Grade 3	0 0%	0 0%
Leukocytes, Grade 4	0 0%	0 0%
Neutrophils, Grades 1 to 4	14 3.9%	6 1.7%
Neutrophils, Grades 2 to 4	4 1.1%	2 0.6%
Neutrophils, Grades 3 to 4	1 0.3%	1 0.3%
Neutrophils, Grade 1	10 2.8%	4 1.1%
Neutrophils, Grade 2	3 0.8%	1 0.3%
Neutrophils, Grade 3	1 0.3%	1 0.3%
Neutrophils, Grade 4	0 0%	0 0%
Platelets, Grades 1 to 4	11 3.1%	9 2.5%
Platelets, Grades 2 to 4	5 1.4%	5 1.4%
Platelets, Grades 3 to 4	0 0%	0 0%
Platelets, Grade 1	6 1.7%	4 1.1%
Platelets, Grade 2	5 1.4%	5 1.4%
Platelets, Grade 3	0 0%	0 0%
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), Albumin, Alkaline Phosphatase (ALP), Bilirubin, Carbon dioxide (CO2), Cholesterol, Creatine kinase (CPK), Creatinine, Direct Bilirubin, Glomerular filtration rate (GFR), Hypercalcemia, Hyperglycemia, Hyperkalemia, Hypernatremia, Hypocalcemia, Hypoglycemia, Hypokalemia and Hyponatremia, Low density lipid (LDL) Cholesterol, Lactate Dehydrogenase, Lipase and Phosphate. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Only those participants with maximum post-Baseline emergent chemistry toxicities in any of the chemistry parameters have been presented.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description
Safety Population

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

14. Secondary Outcome

Title	Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants who discontinued treatment due to AEs have been reported. Analyses presented herein used a data cut-off date of 19 January 2018 and 22 May 2018, respectively, for the Week 24 database freeze and Week 48 database freeze), i.e. may include data collected after a participant's Week 24 or 48 visit, respectively.
Time Frame	Weeks 24 and 48

Outcome Measure Data

Analysis Population Description
Safety Population

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

15. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Serum Cystatin C, Week 24, n=345,345	-0.04 (0.005)	0.00 (0.005)
Serum Cystatin C, Week 48, n=335,336	-0.05 (0.005)	-0.04 (0.006)
Serum RBP, Week 24, n=345,343	1.2 (0.42)	1.4 (0.48)
Serum RBP, Week 48, n=334, 334	0.6 (0.45)	-0.1 (0.42)

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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95% -0.05 to -0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Serum Cystatin C.

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	0.022
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95% -0.03 to 0.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Serum Cystatin C.

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	0.797
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95% -1.4 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Serum RBP

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	0.258
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95% -0.5 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Serum RBP

16. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
GFR Cystatin C adjusted, Week 24, n=345,345	3.8 (0.66)	0.2 (0.65)
GFR Cystatin C adjusted, Week 48, n=335,336	5.4 (0.64)	3.6 (0.64)
GFR creatinine adjusted, Week 24, n=346,344	-12.0 (0.64)	-15.4 (0.59)
GFR creatinine adjusted, Week 48, n=335, 337	-12.1 (0.60)	-15.4 (0.61)

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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.6
	Confidence Interval	(2-Sided) 95% 1.8 to 5.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. GFR Cystatin C adjusted.

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	0.056
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95% 0.0 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. GFR Cystatin C adjusted.

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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 95% 1.7 to 5.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. GFR creatinine adjusted.

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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.3
	Confidence Interval	(2-Sided) 95% 1.6 to 5.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. GFR creatinine adjusted.

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Serum or Plasma Creatinine, Week 24, n=346, 344	10.51 (0.548)	13.53 (0.507)
Serum or Plasma Creatinine, Week 48, n=335, 337	10.32 (0.519)	13.44 (0.540)

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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.02
	Confidence Interval	(2-Sided) 95% -4.49 to -1.55
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Serum Plasma Creatinine

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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.12
	Confidence Interval	(2-Sided) 95% -4.59 to -1.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Serum Plasma creatinine

18. Secondary Outcome

Title	Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48
Description	Blood and/or urine were collected to perform evaluation of renal inflammation biomarkers: Urine and Serum B2M, Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine. Baseline value was the latest pre-dose assessment. Change from Baseline was performed on log-transformed data. Ratio to Baseline was calculated as ratio of post-dose visit value over Baseline value. Geometric mean ratio and 95% CI of geometric mean ratio have been presented. Biomarkers were Adjusted for treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, loge transformed Baseline biomarker value, treatment and visit interaction, and loge transformed Baseline biomarker value and visit interaction; with visit as the repeated factor.
Time Frame	Baseline and Weeks 24, 48

Outcome Measure Data

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

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Serum B2M, Week 24, n=344,346	0.809	0.882
Serum B2M, Week 48, n=335,336	0.811	0.887
Urine B2M, Week 24, n=124,106	0.844	1.129
Urine B2M, Week 48, n=109, 103	0.917	1.323
Urine Albumin/Creatinine, Week 24, n=259, 251	0.907	1.021
Urine Albumin/Creatinine , Week 48, n=249, 240	0.911	0.971
Urine B2M/Urine Creatinine , Week 24, n=122, 104	0.880	1.126
Urine B2M/Urine Creatinine , Week 48, n=108, 103	0.969	1.307
Urine Phosphate, Week 24, n=343, 340	1.041	1.063
Urine Phosphate, Week 48, n=335, 332	1.121	1.056
Urine Protein/Creatinine, Week 24, n=263,279	0.818	0.991
Urine Protein/Creatinine , Week 48, n=259, 261	0.866	1.007
Urine RBP 4, Week 24, n=340, 338	0.656	0.824
Urine RBP 4, Week 48, n=333, 331	0.740	0.819
Urine RBP 4/Urine Creatinine, Week 24, n=338, 335	0.670	0.811
Urine RBP 4/Urine Creatinine, Week 48, n=331, 328	0.749	0.844

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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.917
	Confidence Interval	(2-Sided) 95% 0.893 to 0.941
	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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.914
	Confidence Interval	(2-Sided) 95% 0.890 to 0.939
	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	0.002
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.748
	Confidence Interval	(2-Sided) 95% 0.621 to 0.901
	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	0.005
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.693
	Confidence Interval	(2-Sided) 95% 0.538 to 0.892
	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	0.036
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.889
	Confidence Interval	(2-Sided) 95% 0.796 to 0.992
	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	0.308
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.938
	Confidence Interval	(2-Sided) 95% 0.830 to 1.061
	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	0.007
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.781
	Confidence Interval	(2-Sided) 95% 0.654 to 0.934
	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	0.012
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.742
	Confidence Interval	(2-Sided) 95% 0.588 to 0.935
	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	0.728
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.979
	Confidence Interval	(2-Sided) 95% 0.868 to 1.104
	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	0.311
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	1.062
	Confidence Interval	(2-Sided) 95% 0.945 to 1.194
	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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.826
	Confidence Interval	(2-Sided) 95% 0.769 to 0.887
	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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.860
	Confidence Interval	(2-Sided) 95% 0.795 to 0.930
	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	0.003
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.796
	Confidence Interval	(2-Sided) 95% 0.683 to 0.927
	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	0.200
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.903
	Confidence Interval	(2-Sided) 95% 0.773 to 1.056
	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	0.003
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.826
	Confidence Interval	(2-Sided) 95% 0.728 to 0.936
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Urine RBP/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	0.052
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Ratio of geometric means
	Estimated Value	0.888
	Confidence Interval	(2-Sided) 95% 0.787 to 1.001
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Urine RBP/Urine Creatinine

19. Secondary Outcome

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

Outcome Measure Data

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

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

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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.66
	Confidence Interval	(2-Sided) 95% -3.25 to -2.08
	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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.09
	Confidence Interval	(2-Sided) 95% -3.75 to -2.44
	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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.67
	Confidence Interval	(2-Sided) 95% -5.63 to -3.71
	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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5.90
	Confidence Interval	(2-Sided) 95% -6.89 to -4.91
	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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-13.5
	Confidence Interval	(2-Sided) 95% -16.4 to -10.6
	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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-12.8
	Confidence Interval	(2-Sided) 95% -15.4 to -10.2
	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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1270
	Confidence Interval	(2-Sided) 95% -0.1640 to -0.0900
	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	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2043
	Confidence Interval	(2-Sided) 95% -0.2532 to -0.1554
	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. Adjusted mean and standard error is presented. Adjusted mean is the estimated mean change from Baseline at each visit in each arm calculated from a repeated measures model adjusting for: treatment, visit, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count (factor), age, sex (factor), race (factor), BMI (factor), smoking status (factor), current Vitamin D use (factor), Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Baseline value is defined as the latest pre-dose assessment. Change from Baseline was calculated as value at the indicated time point minus Baseline value.
Time Frame	Baseline and at Weeks 24, 48

Outcome Measure Data

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

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Serum Vitamin D, Week 24, n=346, 344	11.2 (1.08)	15.4 (1.33)
Serum Vitamin D, Week 48, n=336, 335	0.3 (0.92)	0.4 (1.01)

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	0.015
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.2
	Confidence Interval	(2-Sided) 95% -7.5 to -0.8
	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	0.960
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95% -2.8 to 2.6
	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 High Density Lipoprotein (HDL) Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48
Description	Blood samples were collected to perform evaluation of fasting lipids which included Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides. Baseline value is defined as the latest pre-dose assessment (Day 1). Percentage change from Baseline was calculated as 100 multiplied by ([post-dose visit value minus Baseline value] divided by Baseline value).
Time Frame	Baseline and at Weeks 24, 48

Outcome Measure Data

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

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

22. Secondary Outcome

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

Outcome Measure Data

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

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

23. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Week 24, n=313, 320	4 1.1%	0 0%
Week 48, n=324, 332	4 1.1%	2 0.6%

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	Fisher Exact
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.5
	Confidence Interval	(2-Sided) 95% 1.5 to 5.6
	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	0.037
	Comments
	Method	Fisher Exact
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.8
	Confidence Interval	(2-Sided) 95% 0.2 to 5.4
	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 cells/mm^3, >200 cells/mm^3 for group-1), Baseline HIV-1 RNA (<=100000, >100000 c/mL) and Race (White, African American/African heritage, Asian other).
Time Frame	Week 24

Outcome Measure Data

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

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Baseline CD4+ cell count Group-1, <=200,n=32,26	78 21.7%	92 25.6%
Baseline CD4+ cell count Group-1, >200,n=328,333	95 26.4%	94 26.2%
Female, n=54, 46	93 25.8%	89 24.8%
Male, n=306, 313	94 26.1%	95 26.5%
Age, <35,n= 209, 203	93 25.8%	94 26.2%
Age, 35 to <50,n=115, 122	96 26.7%	94 26.2%
Age, >=50, n=36, 34	94 26.1%	91 25.3%
Baseline plasma HIV-1 RNA, <=100000,n=294,282	94 26.1%	95 26.5%
Baseline plasma HIV-1 RNA, >100000,n=66, 77	92 25.6%	90 25.1%
Race, White, n=237,249	95 26.4%	95 26.5%
Race, African American/African H., n=55, 40	89 24.7%	90 25.1%
Race, Asian, n=34, 30	97 26.9%	90 25.1%
Race, Other, n=34, 40	91 25.3%	93 25.9%

25. Secondary Outcome

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

Outcome Measure Data

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

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Baseline CD4+ cell count Group-1, <=200,n=32, 26	78 21.7%	96 26.7%
Baseline CD4+ cell count Group-1, >200,n=328,333	95 26.4%	94 26.2%
Female, n=54, 46	89 24.7%	87 24.2%
Male, n=306, 313	94 26.1%	95 26.5%
Age, <35,n= 209,203	92 25.6%	94 26.2%
Age, 35 to <50,n=115, 122	97 26.9%	94 26.2%
Age, >=50, n=36, 34	89 24.7%	94 26.2%
Baseline plasma HIV-1 RNA, <=100000,n=294,282	92 25.6%	95 26.5%
Baseline plasma HIV-1 RNA, >100000,n=66, 77	97 26.9%	90 25.1%
Race, White, n=237,249	96 26.7%	96 26.7%
Race, African American/African H., n=55, 40	80 22.2%	88 24.5%
Race, Asian, n=34, 30	97 26.9%	90 25.1%
Race, Other, n=34, 40	88 24.4%	90 25.1%

26. Secondary Outcome

Title	Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups
Description	CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is the the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the inidicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from Analysis of Covariance (ANCOVA) model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only.
Time Frame	Baseline (Day 1) and Week 48

Outcome Measure Data

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

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

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	6.9
	Confidence Interval	(2-Sided) 95% -22.7 to 36.6
	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, Baseline plasma HIV-1 RNA, and treatment and relevant Baseline plasma HIV-1 RNA interaction.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	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	13.2
	Confidence Interval	(2-Sided) 95% -46.8 to 73.2
	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, Baseline plasma HIV-1 RNA, and treatment and Baseline plasma HIV-1 RNA interaction.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	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	57.7
	Confidence Interval	(2-Sided) 95% -37.2 to 152.5
	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	4.1
	Confidence Interval	(2-Sided) 95% -23.5 to 31.7
	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	32.5
	Confidence Interval	(2-Sided) 95% -2.7 to 67.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Age Group-1,<35. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	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	-31.5
	Confidence Interval	(2-Sided) 95% -77.1 to 14.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Age Group-1,35 to <50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	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% -81.4 to 91.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Age Group-1,>=50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	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	-27.3
	Confidence Interval	(2-Sided) 95% -100.8 to 46.1
	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	12.8
	Confidence Interval	(2-Sided) 95% -15.7 to 41.2
	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	9.1
	Confidence Interval	(2-Sided) 95% -22.9 to 41.1
	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, and treatment and race 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	-19.8
	Confidence Interval	(2-Sided) 95% -97.1 to 57.6
	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, and treatment and race 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	15.7
	Confidence Interval	(2-Sided) 95% -74.4 to 105.9
	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, and treatment and race 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	35.0
	Confidence Interval	(2-Sided) 95% -49.0 to 119.0
	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, and treatment and race interaction.

27. Secondary Outcome

Title	Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups
Description	CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Blood samples were collected at specified time points to assess CD4+. It was evaluated by flow cytometry. Baseline value is the the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented for subgroups (Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, Age group, Gender and race). For each subgroup, adjusted mean is the estimated mean change from Baseline in each arm calculated from ANCOVA model adjusting for the following covariates/factors: treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, subgroup, and treatment and relevant subgroup interaction. For CD4+ cell count subgroup, Baseline CD4+ cell count group is included as a factor only.
Time Frame	Baseline (Day 1) and Week 24

Outcome Measure Data

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

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

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	37.80
	Confidence Interval	(2-Sided) 95% 9.98 to 65.62
	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, Baseline plasma HIV-1 RNA, and treatment and relevant Baseline plasma HIV-1 RNA interaction.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	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	-26.81
	Confidence Interval	(2-Sided) 95% -82.72 to 29.10
	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, Baseline plasma HIV-1 RNA, and treatment and Baseline plasma HIV-1 RNA interaction.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	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	61.72
	Confidence Interval	(2-Sided) 95% -26.94 to 150.39
	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	22.57
	Confidence Interval	(2-Sided) 95% -3.42 to 48.55
	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	38.99
	Confidence Interval	(2-Sided) 95% 5.88 to 72.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	Age Group,<35. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	DTG + 3TC, DTG + TDF/FTC
	Comments
	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	-9.90
	Confidence Interval	(2-Sided) 95% -53.10 to 33.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	Age Group,35 to <50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

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	65.53
	Confidence Interval	(2-Sided) 95% -14.43 to 145.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	Age Group,>=50. Following covariates/factors were adjusted: Treatment, Baseline plasma HIV-1 RNA (factor), Baseline CD4+ cell count, age, and treatment and age interaction.

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	59.66
	Confidence Interval	(2-Sided) 95% -8.62 to 127.94
	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	19.23
	Confidence Interval	(2-Sided) 95% -7.65 to 46.10
	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	13.90
	Confidence Interval	(2-Sided) 95% -16.35 to 44.15
	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, and treatment and race 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	68.74
	Confidence Interval	(2-Sided) 95% -1.24 to 138.72
	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, and treatment and race 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	12.93
	Confidence Interval	(2-Sided) 95% -71.90 to 97.75
	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, and treatment and race 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	59.19
	Confidence Interval	(2-Sided) 95% -19.73 to 138.11
	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, and treatment and race interaction.

28. Secondary Outcome

Title	Change From Baseline in European Quality of Life [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. MMRM was run on LOCF dataset. Baseline was the latest pre-dose assessment and change from Baseline=post-dose value minus Baseline value. Only those participants available at the specified time points were analyzed.
Time Frame	Baseline (Day 1) and Weeks 4, 24, 48

Outcome Measure Data

Analysis Population Description
ITT-E Population. (represented by n=x in the category titles).

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Week 4, n=359, 355	0.0111 (0.00326)	0.0130 (0.00510)
Week 24, n=360, 358	0.0207 (0.00310)	0.0203 (0.00347)
Week 48, n=360, 358	0.0189 (0.00362)	0.0208 (0.00342)

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	0.759
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.0019
	Confidence Interval	(2-Sided) 95% -0.0137 to 0.0100
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 4. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA , Baseline CD4+ cell count , and Baseline EQ-5D utility, treatmentvisit and Baseline EQ-5D utilityvisit as factors and covariate, 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	0.943
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0003
	Confidence Interval	(2-Sided) 95% -0.0088 to 0.0095
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA , Baseline CD4+ cell count , and Baseline EQ-5D utility, treatmentvisit and Baseline EQ-5D utilityvisit as factors and covariate, 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	0.703
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.0019
	Confidence Interval	(2-Sided) 95% -0.0117 to 0.0079
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA , Baseline CD4+ cell count , and Baseline EQ-5D utility, treatmentvisit and Baseline EQ-5D utilityvisit as factors and covariate, 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 provided a profile of participant function and a global health state rating. The five-item measure has one question assessing each of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression and 5 levels for each dimension including 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L included EQ visual Analogue scale (EQ VAS) 'Thermometer' which provided Self-rated current health status. Score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). MMRM was run on the LOCF dataset, using the observed margins (OM) option. Baseline was the latest pre-dose assessment value and change from Baseline=post-dose value minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=x in the category titles).
Time Frame	Baseline (Day 1) and Weeks 4, 24, 48

Outcome Measure Data

Analysis Population Description
ITT-E Population.

Arm/Group Title	DTG + 3TC	DTG + TDF/FTC
Arm/Group Description	Participants received a two-drug regimen of DTG + 3TC administered orally, once daily for 48 weeks.	Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks.
Measure Participants	360	359
Week 4, n=358, 355	1.8 (0.50)	3.1 (0.41)
Week 24, n=359, 358	3.9 (0.43)	4.5 (0.48)
Week 48, n=359, 358	4.0 (0.43)	4.6 (0.48)

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	0.045
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95% -2.6 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 4. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count and Baseline EQ-5D utility, treatmentvisit and Baseline EQ-5D utilityvisit as factors and covariate, 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	0.358
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95% -1.9 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 24. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count and Baseline EQ-5D utility, treatmentvisit and Baseline EQ-5D utilityvisit as factors and covariate, 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	0.328
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95% -1.9 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Week 48. Covariates adjusted: Treatment, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, and Baseline EQ-5D utility, treatmentvisit and Baseline EQ-5D utilityvisit as factors and covariate, with visit as the repeated factor.

Adverse Events

	DTG + 3TC		DTG + TDF/FTC
Time Frame	Post-Baseline SAEs and non-SAEs) 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 DTG + 3TC administered orally, once daily for 48 weeks		Participants received a three-drug regimen of DTG + TDF/FTC FDC administered orally, once daily for 48 weeks
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/360 (0.6%)		0/359 (0%)
Serious Adverse Events
	DTG + 3TC		DTG + TDF/FTC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/360 (8.1%)		33/359 (9.2%)
Cardiac disorders
Acute myocardial infarction	1/360 (0.3%)	1	0/359 (0%)	0
Tachycardia	0/360 (0%)	0	1/359 (0.3%)	1
Eye disorders
Ophthalmic vein thrombosis	1/360 (0.3%)	1	0/359 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/360 (0.3%)	1	1/359 (0.3%)	1
Abdominal hernia	0/360 (0%)	0	1/359 (0.3%)	1
Gastrointestinal haemorrhage	1/360 (0.3%)	1	0/359 (0%)	0
Hepatobiliary disorders
Cholecystitis acute	0/360 (0%)	0	2/359 (0.6%)	2
Cholelithiasis	0/360 (0%)	0	1/359 (0.3%)	1
Hepatotoxicity	1/360 (0.3%)	1	0/359 (0%)	0
Infections and infestations
Hepatitis A	3/360 (0.8%)	3	3/359 (0.8%)	3
Acute hepatitis C	1/360 (0.3%)	1	1/359 (0.3%)	1
Pneumonia	1/360 (0.3%)	1	1/359 (0.3%)	1
Anal abscess	0/360 (0%)	0	1/359 (0.3%)	1
Bacterial colitis	0/360 (0%)	0	1/359 (0.3%)	1
Epididymitis	1/360 (0.3%)	1	0/359 (0%)	0
Erysipelas	0/360 (0%)	0	1/359 (0.3%)	1
Pneumonia bacterial	0/360 (0%)	0	1/359 (0.3%)	1
Salmonellosis	1/360 (0.3%)	1	0/359 (0%)	0
Soft tissue infection	0/360 (0%)	0	1/359 (0.3%)	1
Tuberculous pleurisy	1/360 (0.3%)	1	0/359 (0%)	0
Urinary tract infection	1/360 (0.3%)	1	0/359 (0%)	0
Varicella zoster virus infection	1/360 (0.3%)	1	0/359 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/360 (0%)	0	1/359 (0.3%)	1
Fracture	1/360 (0.3%)	1	0/359 (0%)	0
Fracture of penis	0/360 (0%)	0	1/359 (0.3%)	1
Injury	1/360 (0.3%)	1	0/359 (0%)	0
Intentional overdose	0/360 (0%)	0	1/359 (0.3%)	1
Lower limb fracture	1/360 (0.3%)	1	0/359 (0%)	0
Multiple fractures	0/360 (0%)	0	1/359 (0.3%)	1
Multiple injuries	0/360 (0%)	0	1/359 (0.3%)	1
Penetrating abdominal trauma	0/360 (0%)	0	1/359 (0.3%)	1
Post procedural complication	0/360 (0%)	0	1/359 (0.3%)	1
Radius fracture	1/360 (0.3%)	1	0/359 (0%)	0
Thermal burn	1/360 (0.3%)	1	0/359 (0%)	0
Upper limb fracture	0/360 (0%)	0	1/359 (0.3%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/360 (0%)	0	1/359 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts	2/360 (0.6%)	2	3/359 (0.8%)	3
Anal cancer stage 0	1/360 (0.3%)	1	0/359 (0%)	0
B-cell lymphoma	1/360 (0.3%)	1	0/359 (0%)	0
Basal cell carcinoma	0/360 (0%)	0	1/359 (0.3%)	1
Burkitt's lymphoma	1/360 (0.3%)	1	0/359 (0%)	0
Non-Hodgkin's lymphoma	0/360 (0%)	0	1/359 (0.3%)	1
Nervous system disorders
Sciatica	1/360 (0.3%)	1	1/359 (0.3%)	1
Generalised tonic-clonic seizure	1/360 (0.3%)	1	0/359 (0%)	0
Seizure	0/360 (0%)	0	1/359 (0.3%)	1
Psychiatric disorders
Suicide attempt	3/360 (0.8%)	3	1/359 (0.3%)	1
Suicidal ideation	1/360 (0.3%)	1	2/359 (0.6%)	2
Acute psychosis	0/360 (0%)	0	1/359 (0.3%)	1
Alcoholic psychosis	0/360 (0%)	0	1/359 (0.3%)	1
Renal and urinary disorders
Urethral meatus stenosis	0/360 (0%)	0	1/359 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	0/360 (0%)	0	1/359 (0.3%)	1
Other (Not Including Serious) Adverse Events
	DTG + 3TC		DTG + TDF/FTC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	189/360 (52.5%)		215/359 (59.9%)
Gastrointestinal disorders
Diarrhoea	35/360 (9.7%)	40	35/359 (9.7%)	38
Nausea	15/360 (4.2%)	15	23/359 (6.4%)	24
Abdominal pain	6/360 (1.7%)	6	12/359 (3.3%)	13
Haemorrhoids	8/360 (2.2%)	8	10/359 (2.8%)	10
Constipation	8/360 (2.2%)	9	8/359 (2.2%)	8
Toothache	7/360 (1.9%)	7	9/359 (2.5%)	9
Vomiting	8/360 (2.2%)	8	8/359 (2.2%)	8
General disorders
Fatigue	10/360 (2.8%)	12	6/359 (1.7%)	6
Influenza like illness	10/360 (2.8%)	11	6/359 (1.7%)	6
Pyrexia	8/360 (2.2%)	8	5/359 (1.4%)	6
Infections and infestations
Nasopharyngitis	22/360 (6.1%)	28	41/359 (11.4%)	47
Upper respiratory tract infection	32/360 (8.9%)	38	22/359 (6.1%)	26
Pharyngitis	13/360 (3.6%)	15	19/359 (5.3%)	19
Influenza	8/360 (2.2%)	8	17/359 (4.7%)	19
Syphilis	10/360 (2.8%)	12	12/359 (3.3%)	12
Respiratory tract infection viral	11/360 (3.1%)	13	9/359 (2.5%)	13
Bronchitis	8/360 (2.2%)	9	10/359 (2.8%)	11
Gastroenteritis	7/360 (1.9%)	7	11/359 (3.1%)	13
Tonsillitis	10/360 (2.8%)	10	8/359 (2.2%)	9
Gonorrhoea	9/360 (2.5%)	9	7/359 (1.9%)	8
Chlamydial infection	7/360 (1.9%)	8	8/359 (2.2%)	8
Rhinitis	2/360 (0.6%)	2	9/359 (2.5%)	9
Genital herpes	1/360 (0.3%)	1	8/359 (2.2%)	12
Metabolism and nutrition disorders
Vitamin D deficiency	8/360 (2.2%)	8	4/359 (1.1%)	4
Musculoskeletal and connective tissue disorders
Back pain	16/360 (4.4%)	18	12/359 (3.3%)	14
Arthralgia	10/360 (2.8%)	11	15/359 (4.2%)	15
Nervous system disorders
Headache	31/360 (8.6%)	38	31/359 (8.6%)	36
Dizziness	7/360 (1.9%)	9	13/359 (3.6%)	14
Psychiatric disorders
Insomnia	11/360 (3.1%)	11	16/359 (4.5%)	19
Anxiety	9/360 (2.5%)	9	11/359 (3.1%)	11
Depression	6/360 (1.7%)	6	8/359 (2.2%)	8
Renal and urinary disorders
Dysuria	8/360 (2.2%)	8	2/359 (0.6%)	2
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	11/360 (3.1%)	13	9/359 (2.5%)	9
Cough	7/360 (1.9%)	7	8/359 (2.2%)	8
Skin and subcutaneous tissue disorders
Rash	4/360 (1.1%)	4	10/359 (2.8%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title	GSK Response Center
Organization	GlaxoSmithKline
Phone	866-435-7343
Email	GSKClinicalSupportHD@gsk.com

Responsible Party:

ViiV Healthcare

ClinicalTrials.gov Identifier:

NCT02831764

Other Study ID Numbers:

205543
2016-000459-28

First Posted:

Jul 13, 2016

Last Update Posted:

Aug 11, 2022

Last Verified:

Jul 1, 2022