HIV-1-infection

Primary • To demonstrate non-inferior antiviral activity of DTG + 3TC versus DTG + TDF/FTC at 48 weeks in HIV-1-infected, ART-naïve subjects Secondary • To demonstrate the antiviral activity of DTG + 3TC versus DTG + TDF/FTC at 24, 96 and 144 weeks • To evaluate the antiviral activity, immunological effects, and incidence of disease progression (HIV-associated conditions, AIDS and death) of DTG + 3TC compared to DTG + TDF/FTC over time • To assess viral resistance in subjects meeting confirmed virologic withdrawal (CVW) criteria • To evaluate the safety and tolerability of DTG + 3TC compared to DTG + TDF/FTC over time • To evaluate renal biomarkers (in urine and blood) and bone biomarkers (in blood) in subjects treated with DTG + 3TC compared to DTG + TDF/FTC • To evaluate the effects of DTG + 3TC on fasting lipids compared to DTG + TDF/FTC over time • To evaluate the effect of patient demographics and baseline characteristics (e.g. demographic factors, HIV-1 subtype, baseline CD4+ cell count) on response to DTG + 3TC compared to DTG + TDF/FTC over time • To assess change in health-related quality-of-life for subjects treated with DTG plus 3TC compared to DTG + TDF/FTC

Dolutegravir(DTG),Lamivudine(3TC).Tenofovir(TDF )/emtricitabine(FTC)

Dolutegravir(DTG)
Lamivudine(3TC)

oral tablet
oral tablet

50mg/Tablet
300mg/Capsule;300mg/Tablet

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

Secondary Outcome Measures :
1. Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24 [ Time Frame: Week 24 ]
2. Time to Viral Suppression (HIV-1 RNA <50 c/mL) [ Time Frame: Up to Week 48 ]
3. CD4+ Cell Counts at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
4. Changes From Baseline in CD4+ Cell Counts at Week 24 and 48 [ Time Frame: Baseline (Day 1) and Weeks 24, 48 ]
5. Number of Participants With HIV-1 Disease Progression [ Time Frame: Up to Week 48 ]
6. Number of Participants With Treatment-emergent Genotypic Resistance [ Time Frame: Up to Week 48 ]
7. Number of Participants With Treatment-emergent Phenotypic Resistance [ Time Frame: Up to Week 48 ]
8. Number of Participants With Any Adverse Event (AE) and Serious AE (SAE) [ Time Frame: Up to Week 48 ]
9. Number of Participants With AEs by Their Severity Grades [ Time Frame: Up to Week 48 ]
10. Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade [ Time Frame: Up to Week 48 ]
11. Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities [ Time Frame: Up to Week 48 ]
12. Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities [ Time Frame: Up to Week 48 ]
13. Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48 [ Time Frame: Up to Week 48 ]
14. Change From Baseline in Renal Biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48 [ Time Frame: Baseline and at Weeks 24, 48 ]
15. Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR From Creatinine Adjusted Using CKD-EPI at Weeks 24, 48 [ Time Frame: Baseline and at Weeks 24, 48 ]
16. Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Weeks 24, 48 [ Time Frame: Baseline and at Weeks 24, 48 ]
17. Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 [ Time Frame: Baseline and at Weeks 24, 48 ]
18. Change From Baseline in Bone Biomarkers-Serum Bone Specific Alkaline Phosphatase (Bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48 [ Time Frame: Baseline and at Weeks 24, 48 ]
19. Change From Baseline in Bone Biomarker-Serum Vitamin D at Weeks 24, 48 [ Time Frame: Baseline and at Weeks 24, 48 ]
20. Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48 [ Time Frame: Baseline (Day 1) and at Weeks 24, 48 ]
21. Percentage Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48 [ Time Frame: Baseline (Day 1) and at Weeks 24, 48 ]
22. Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Weeks 24, 48 [ Time Frame: Up to Week 48 ]
23. Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 [ Time Frame: Week 24 ]
24. Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 [ Time Frame: Week 48 ]
25. Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups [ Time Frame: Baseline (Day 1) and Week 48 ]
26. Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups [ Time Frame: Baseline (Day 1) and Week 24 ]
27. Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Utility Score at Weeks 4, 24, 48 [ Time Frame: Baseline and Weeks 4, 24, 48 ]
28. Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24 48 [ Time Frame: Baseline (Day 1) and Weeks 4, 24, 48 ]

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
o 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
o Non reproductive premenopausal women are those with 12 months of spontaneous amenorrhea and >=45 years of age
o 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:
o Radiation therapy,
o Cytotoxic chemotherapeutic agents,
o 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