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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02831673

Registration number

NCT02831673

Ethics application status

Date submitted

8/07/2016

Date registered

13/07/2016

Date last updated

24/08/2023

Titles & IDs

Public title

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

Scientific title

A Phase III, Randomised, Double Blind, Multicentre, Parallel Group, Non Inferiority Study Evaluating the Efficacy, Safety, and Tolerability of Dolutegravir Plus Lamivudine Compared to Dolutegravir Plus Tenofovir/Emtricitabine in Human Immunodeficiency Virus 1 Infected Treatment naïve Adults

Secondary ID [1]

2015-004418-95

Secondary ID [2]

204861

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Infection, Human Immunodeficiency Virus

HIV Infections

Condition category

Condition code

Infection

Studies of infection and infectious agents

Infection

Other infectious diseases

Infection

Sexually transmitted infections

Infection

Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - Dolutegravir (DTG)
Treatment: Drugs - Lamivudine (3TC)
Treatment: Drugs - Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC FDC)

Experimental: DTG + 3TC (50 mg+300 mg) - Eligible participants 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 participant no longer derives clinical benefit, or (iv) the participant meets a protocol defined reason for discontinuation, or (v) development of the DTG plus 3TC dual regimen is terminated.

Active comparator: DTG + TDF/FTC FDC (50 mg+300/200 mg) - Eligible participants 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).

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

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

Assessment method [1]

Percentage of participants with HIV-1 RNA\<50 c/mL was obtained using Food and Drug Administration (FDA) Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest. This endpoint was analyzed using a stratified analysis with Cochran-Mantel-Haenszel (CMH) weights. Intent-To-Treat Exposed (ITT-E) Population was used which comprised of all randomized participants who received at least one dose of study treatment. Percentage values are rounded to the nearest whole digit.

Timepoint [1]

Week 48

Secondary outcome [1]

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

Assessment method [1]

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

Timepoint [1]

Week 24

Secondary outcome [2]

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

Assessment method [2]

Timepoint [2]

Week 96

Secondary outcome [3]

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

Assessment method [3]

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

Timepoint [3]

Week 144

Secondary outcome [4]

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

Assessment method [4]

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.

Timepoint [4]

Up to Week 144

Secondary outcome [5]

CD4+ Cell Counts at Weeks 24 and 48

Assessment method [5]

Timepoint [5]

Weeks 24 and 48

Secondary outcome [6]

CD4+ Cell Counts at Week 96

Assessment method [6]

Timepoint [6]

Week 96

Secondary outcome [7]

CD4+ Cell Counts at Week 144

Assessment method [7]

Timepoint [7]

Week 144

Secondary outcome [8]

Changes From Baseline in CD4+ Cell Counts at Week 24 and 48

Assessment method [8]

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

Timepoint [8]

Baseline (Day 1) and Weeks 24, 48

Secondary outcome [9]

Changes From Baseline in CD4+ Cell Counts at Week 96

Assessment method [9]

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

Timepoint [9]

Baseline (Day 1) and Week 96

Secondary outcome [10]

Changes From Baseline in CD4+ Cell Counts at Week 144

Assessment method [10]

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

Timepoint [10]

Baseline (Day 1) and Week 144

Secondary outcome [11]

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

Assessment method [11]

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.

Timepoint [11]

Up to Week 144

Secondary outcome [12]

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

Assessment method [12]

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

Timepoint [12]

Up to Week 144

Secondary outcome [13]

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

Assessment method [13]

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

Timepoint [13]

Up to Week 144

Secondary outcome [14]

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

Assessment method [14]

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or protocol defined event associated with liver injury and impaired liver function were categorized as SAE. Safety Population was used which comprised of all participants who received at least one dose of study treatment.

Timepoint [14]

Up to Week 148

Secondary outcome [15]

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

Assessment method [15]

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

Timepoint [15]

Up to Week 144

Secondary outcome [16]

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

Assessment method [16]

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.

Timepoint [16]

Up to Week 144

Secondary outcome [17]

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

Assessment method [17]

Blood samples were collected up to Week 144 for assessment of hemoglobin, leukocytes, neutrophils and platelets. Any abnormality was graded according to DAIDS toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). The higher the grade, the more severe the symptoms. Only those participants with maximum post-Baseline emergent hematology toxicities in any of the listed hematology parameters have been presented.

Timepoint [17]

Up to Week 144

Secondary outcome [18]

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

Assessment method [18]

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

Timepoint [18]

Up to Week 144

Secondary outcome [19]

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

Assessment method [19]

Timepoint [19]

Up to Week 24, Week 48 and Week 96

Secondary outcome [20]

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

Assessment method [20]

Timepoint [20]

Up to Week 144

Secondary outcome [21]

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

Assessment method [21]

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

Timepoint [21]

Baseline (Day 1) and at Weeks 24, 48

Secondary outcome [22]

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

Assessment method [22]

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

Timepoint [22]

Baseline (Day 1) and at Week 96

Secondary outcome [23]

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

Assessment method [23]

Blood samples were collected to perform evaluation of renal biomarkers which included Serum Cystatin C. Baseline value is the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Biomarkers were adjusted for treatment, visit, Baseline plasma HIV-1 RNA, Baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, Baseline biomarker value, treatment and visit interaction, and Baseline biomarker value and visit interaction; with visit as the repeated factor. Adjusted mean and standard error is presented.

Timepoint [23]

Baseline (Day 1) and at Week 144

Secondary outcome [24]

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

Assessment method [24]

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

Timepoint [24]

Baseline (Day 1) and at Week 96

Secondary outcome [25]

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

Assessment method [25]

Timepoint [25]

Baseline (Day 1) and at Week 144

Secondary outcome [26]

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

Assessment method [26]

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

Timepoint [26]

Baseline (Day 1) and at Weeks 24, 48

Secondary outcome [27]

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

Assessment method [27]

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

Timepoint [27]

Baseline (Day 1) and at Week 96

Secondary outcome [28]

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

Assessment method [28]

Timepoint [28]

Baseline (Day 1) and at Week 144

Secondary outcome [29]

Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Weeks 24, 48

Assessment method [29]

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

Timepoint [29]

Baseline (Day 1) and at Weeks 24, 48

Secondary outcome [30]

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

Assessment method [30]

Timepoint [30]

Baseline (Day 1) and at Week 96

Secondary outcome [31]

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

Assessment method [31]

Timepoint [31]

Baseline (Day 1) and at Week 144

Secondary outcome [32]

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

Assessment method [32]

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

Timepoint [32]

Baseline (Day 1) and at Weeks 24, 48

Secondary outcome [33]

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

Assessment method [33]

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

Timepoint [33]

Baseline (Day 1) and Week 96

Secondary outcome [34]

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

Assessment method [34]

Timepoint [34]

Baseline (Day 1) and Week 144

Secondary outcome [35]

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

Assessment method [35]

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

Timepoint [35]

Baseline (Day 1) and at Weeks 24, 48

Secondary outcome [36]

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

Assessment method [36]

Timepoint [36]

Baseline (Day 1) and at Week 96

Secondary outcome [37]

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

Assessment method [37]

Timepoint [37]

Baseline (Day 1) and at Week 144

Secondary outcome [38]

Change From Baseline in Bone Biomarker-Serum Vitamin D at Weeks 24, 48

Assessment method [38]

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

Timepoint [38]

Baseline (Day 1) and at Weeks 24, 48

Secondary outcome [39]

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

Assessment method [39]

Timepoint [39]

Baseline (Day 1) and at Week 96

Secondary outcome [40]

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

Assessment method [40]

Timepoint [40]

Baseline (Day 1) and at Week 144

Secondary outcome [41]

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

Assessment method [41]

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).

Timepoint [41]

Baseline (Day 1) and at Weeks 24, 48

Secondary outcome [42]

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

Assessment method [42]

Blood samples were collected to perform evaluation of fasting lipids which included Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides. Baseline value was defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented.

Timepoint [42]

Baseline (Day 1) and at Week 96

Secondary outcome [43]

Assessment method [43]

Blood samples were collected to perform evaluation of fasting lipids which included Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides. Baseline value was defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as value at the indicated time point minus Baseline value. Adjusted mean and standard error is presented.

Timepoint [43]

Baseline (Day 1) and at Week 144

Secondary outcome [44]

Percentage Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48

Assessment method [44]

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

Timepoint [44]

Baseline (Day 1) and at Weeks 24, 48

Secondary outcome [45]

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

Assessment method [45]

Blood samples were collected to perform evaluation of fasting lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio. Baseline value was defined as the latest pre-dose assessment (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value. Adjusted mean and standard error has been presented.

Timepoint [45]

Baseline (Day 1) and at Week 96

Secondary outcome [46]

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

Assessment method [46]

Timepoint [46]

Baseline (Day 1) and at Week 144

Secondary outcome [47]

Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Weeks 24, 48

Assessment method [47]

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

Timepoint [47]

Weeks 24 and Week 48

Secondary outcome [48]

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

Assessment method [48]

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

Timepoint [48]

Week 96

Secondary outcome [49]

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

Assessment method [49]

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

Timepoint [49]

Week 144

Secondary outcome [50]

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

Assessment method [50]

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

Timepoint [50]

Week 24

Secondary outcome [51]

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

Assessment method [51]

Timepoint [51]

Week 48

Secondary outcome [52]

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

Assessment method [52]

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

Timepoint [52]

Week 96

Secondary outcome [53]

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

Assessment method [53]

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

Timepoint [53]

Week 144

Secondary outcome [54]

Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups

Assessment method [54]

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

Timepoint [54]

Baseline (Day 1) and Week 24

Secondary outcome [55]

Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups

Assessment method [55]

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

Timepoint [55]

Baseline (Day 1) and Week 48

Secondary outcome [56]

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

Assessment method [56]

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.

Timepoint [56]

Baseline (Day 1) and Week 96

Secondary outcome [57]

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

Assessment method [57]

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.

Timepoint [57]

Baseline (Day 1) and Week 144

Secondary outcome [58]

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

Assessment method [58]

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

Timepoint [58]

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

Secondary outcome [59]

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

Assessment method [59]

Timepoint [59]

Baseline (Day 1) and Week 96

Secondary outcome [60]

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

Assessment method [60]

Timepoint [60]

Baseline (Day 1) and Week 144

Secondary outcome [61]

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

Assessment method [61]

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

Timepoint [61]

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

Secondary outcome [62]

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

Assessment method [62]

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

Timepoint [62]

Baseline (Day 1) and Week 96

Secondary outcome [63]

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

Assessment method [63]

Timepoint [63]

Baseline (Day 1) and Week 144

Eligibility

Key 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 participant 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 participants with Screening plasma HIV 1 RNA of 1000 c/mL to <=500,000 c/mL
* Participants should be antiretroviral naïve (defined as <=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV 1 infection). Participants 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
* Participant or the participants legal representative capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and the protocol
* Participants enrolled in France: a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

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
* Participants 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:

Participants positive for HBV surface antigen (HBsAg) at screening will be excluded Participants 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, participants 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. Participants 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 participant
* Participants 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
* Participants enrolled in France: the participant 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 participant 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 participants 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

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

21/07/2016

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

15/08/2022

Sample size

Target

Accrual to date

Final

719

Recruitment in Australia

Recruitment state(s)

NSW,QLD

Recruitment hospital [1]

GSK Investigational Site - Darlinghurst

Recruitment hospital [2]

GSK Investigational Site - Sydney

Recruitment hospital [3]

GSK Investigational Site - Fortitude Valley

Recruitment postcode(s) [1]

2010 - Darlinghurst

Recruitment postcode(s) [2]

2010 - Sydney

Recruitment postcode(s) [3]

4006 - Fortitude Valley

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

Arizona

Country [2]

United States of America

State/province [2]

District of Columbia

Country [3]

United States of America

State/province [3]

Florida

Country [4]

United States of America

State/province [4]

Georgia

Country [5]

United States of America

State/province [5]

Indiana

Country [6]

United States of America

State/province [6]

Massachusetts

Country [7]

United States of America

State/province [7]

Michigan

Country [8]

United States of America

State/province [8]

Missouri

Country [9]

United States of America

State/province [9]

North Carolina

Country [10]

United States of America

State/province [10]

Pennsylvania

Country [11]

United States of America

State/province [11]

Rhode Island

Country [12]

United States of America

State/province [12]

Texas

Country [13]

Argentina

State/province [13]

Buenos Aires

Country [14]

Belgium

State/province [14]

Antwerpen

Country [15]

Belgium

State/province [15]

Brussels

Country [16]

Belgium

State/province [16]

Bruxelles

Country [17]

Canada

State/province [17]

Ontario

Country [18]

Canada

State/province [18]

Quebec

Country [19]

France

State/province [19]

Le Kremlin-Bicetre Cedex

Country [20]

France

State/province [20]

Marseille

Country [21]

France

State/province [21]

Paris Cedex 10

Country [22]

France

State/province [22]

Paris Cedex 12

Country [23]

France

State/province [23]

Paris

Country [24]

France

State/province [24]

Toulouse Cedex 9

Country [25]

Germany

State/province [25]

Bayern

Country [26]

Germany

State/province [26]

Nordrhein-Westfalen

Country [27]

Germany

State/province [27]

Berlin

Country [28]

Germany

State/province [28]

Hamburg

Country [29]

Italy

State/province [29]

Emilia-Romagna

Country [30]

Italy

State/province [30]

Liguria

Country [31]

Italy

State/province [31]

Lombardia

Country [32]

Italy

State/province [32]

Padova

Country [33]

Italy

State/province [33]

Reggio Emilia

Country [34]

Italy

State/province [34]

Roma

Country [35]

Korea, Republic of

State/province [35]

Busan

Country [36]

Korea, Republic of

State/province [36]

Daegu

Country [37]

Korea, Republic of

State/province [37]

Seoul

Country [38]

Mexico

State/province [38]

Jalisco

Country [39]

Mexico

State/province [39]

Distrito Federal

Country [40]

Netherlands

State/province [40]

Rotterdam

Country [41]

Portugal

State/province [41]

Coimbra

Country [42]

Portugal

State/province [42]

Lisboa

Country [43]

Portugal

State/province [43]

Porto

Country [44]

Romania

State/province [44]

Cluj-Napoca

Country [45]

Romania

State/province [45]

Galati

Country [46]

Russian Federation

State/province [46]

Ekaterinburg

Country [47]

Russian Federation

State/province [47]

Krasnojarsk

Country [48]

Russian Federation

State/province [48]

Moscow

Country [49]

Russian Federation

State/province [49]

Orel

Country [50]

Russian Federation

State/province [50]

St. Petersburg

Country [51]

Russian Federation

State/province [51]

Toliyatti

Country [52]

South Africa

State/province [52]

Observatory, Cape Town

Country [53]

Spain

State/province [53]

Alicante

Country [54]

Spain

State/province [54]

Badalona

Country [55]

Spain

State/province [55]

Córdoba

Country [56]

Spain

State/province [56]

Elche (Alicante)

Country [57]

Spain

State/province [57]

Madrid

Country [58]

Spain

State/province [58]

Mataró

Country [59]

Spain

State/province [59]

San Sebastian

Country [60]

Spain

State/province [60]

Santiago de Compostela

Country [61]

Spain

State/province [61]

Valencia

Country [62]

Spain

State/province [62]

Vigo

Country [63]

Taiwan

State/province [63]

Kaohsiung

Country [64]

Taiwan

State/province [64]

Taipei

Country [65]

United Kingdom

State/province [65]

London

Country [66]

United Kingdom

State/province [66]

Manchester

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

ViiV Healthcare

Country

Other collaborator category [1]

Commercial sector/industry

Name [1]

PPD

Country [1]

Other collaborator category [2]

Commercial sector/industry

Name [2]

GlaxoSmithKline

Country [2]

Ethics approval

Ethics application status

Summary

Brief summary

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

Trial website

https://clinicaltrials.gov/study/NCT02831673

Trial related presentations / 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. 2019 Jan 12;393(10167):132. doi: 10.1016/S0140-6736(18)33041-1.
Ait-Khaled M, Sierra Madero J, Estrada V, Gulminetti R, Hagins D, Tsai HC, Man C, Sievers J, Grove R, Zolopa A, Wynne B, van Wyk J. Impact of treatment adherence on efficacy of dolutegravir plus lamivudine and dolutegravir plus tenofovir disoproxil fumarate/emtricitabine: pooled analysis of the GEMINI-1 and GEMINI-2 clinical studies. HIV Res Clin Pract. 2021 Dec 9;23(1):9-14. Epub 2021 Dec 16.

Public notes

Contacts

Principal investigator

Name

GSK Clinical Trials

Address

ViiV Healthcare

Country

Phone

Contact person for public queries

Name

Address

Country

Phone

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

Type	Other Details	Attachment
Study protocol
Statistical analysis plan

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02831673

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02831673