Efficacy of Dolutegravir Plus Lamivudine in HIV-1-infected Treatment-naïve Adults Without a Baseline Genotyping Test

This is a 48-week, Phase IV, randomized, open-label, to assess the non-inferior antiviral activity (VL < 50 c/ml) of 2DR DTG+3TC versus 3DR TDF/FTC + DTG over 48 weeks in HIV1 naïve adult patients without baseline GT available at Day 1 visit. Subjects will be stratified by screening HIV-1 RNA (≤100,000 c/mL or >100,000 c/mL) and Screening CD4+ cell count (≤ or >200 cells/mm3).

The study will comprise:

• a 28-day Screening Phase (which may be extended to 35 days to allow receipt of all Screening assessment results).
• an Open-label Randomized Phase (Day 1 to Week 48).

Approximately 200 HIV-1 naïve adult patients will be randomized 1:1 to receive 2DR DTG+3TC versus 3DR TDF/FTC + DTG for 48 weeks.

Inclusion criteria

• Subject should be antiretroviral naïve (defined as <=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV 1 infection).
• Age ≥ 18 years
• Screening plasma HIV-1 RNA ≥1000 c/mL
• CD4 cell count nadir: any value
• Effective contraception for women of childbearing potential.
• Informed consent form signed by patient and investigator

Exclusion criteria

• History of suicide ideation, intention or action.
• Evidence of HBV infection based on the results of testing at Screening* for HBV surface antigen (HBsAg), HBV core antibody (anti-HBc), HBV surface antibody (antiHBs or HBsAb), and HBV DNA as follows: Subjects positive for HBsAg are excluded; Subjects negative for anti-HBs and HBsAg but positive for anti-HBc and positive for HBV DNA are excluded.
• Anticipated need for any HCV therapy during the first 48 weeks of the study.
• Acute symptomatic HIV Infection.
• Any active Opportunistic Infection (category C, CDC 2014).
• Current pregnancy or breastfeeding.
• No effective contraception for the women of childbearing.
• Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening period to verify a result.
• ALT (Alanine Aminotransferase) ≥ 5 x upper limit of normal value (ULN) or AST (Aspartate Aminotransferase) ≥ 3 x ULN and bilirubinemia ≥ 1.5 x ULN (with 35% direct bilirubinemia).
• Unstable liver disease (ascitis, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices or persistent jaundice).
• Creatinine clearance of <50 mL/min/1.73 m2 (Cockroft-Gault method).
• History or presence of allergy to the trial drugs or their components.
• Severe hepatic insufficiency (Child Pugh Class C).
• Any available historical resistance test result.