Hiv, HIV-1-infection
Conditions
Keywords
hiv, antiretroviral treatment, dolutegravir, dual therapy
Brief summary
The purpose of this study is to evaluate the efficacy of DTG + 3TC versus DTG + TDF/FTC over 48 weeks in HIV-1 naive patients in a real life setting with no baseline HIV genotypic resistance testing available.
Detailed description
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.
Interventions
Experimental arm
DRUGEmtricitabine / Tenofovir Disoproxil Pill
Active Comparator
Sponsors
ViiV Healthcare
Fundacion IDEAA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject should be antiretroviral naïve (defined as \<=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV 1 infection). 2. Age ≥ 18 years 3. Screening plasma HIV-1 RNA ≥1000 c/mL 4. CD4 cell count nadir: any value 5. Effective contraception for women of childbearing potential. 6. Informed consent form signed by patient and investigator
Exclusion criteria
1. History of suicide ideation, intention or action. 2. 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. 3. Anticipated need for any HCV therapy during the first 48 weeks of the study. 4. Acute symptomatic HIV Infection. 5. Any active Opportunistic Infection (category C, CDC 2014). 6. Current pregnancy or breastfeeding. 7. No effective contraception for the women of childbearing. 8. Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening period to verify a result. 9. 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). 10. Unstable liver disease (ascitis, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices or persistent jaundice). 11. Creatinine clearance of \<50 mL/min/1.73 m2 (Cockroft-Gault method). 12. History or presence of allergy to the trial drugs or their components. 13. Severe hepatic insufficiency (Child Pugh Class C). 14. Any available historical resistance test result.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Virologic Efficacy | 48 weeks | To demonstrate the non-inferior antiviral activity (VL \< 50 c/ml) of 2DR DTG+3TC versus 3DR TDF/FTC + DTG over 48 weeks in HIV-1 naïve adult patients without baseline genotypic resistance testing available. Endpoint: Proportion of subjects with plasma HIV-1 RNA \<50 copies/mL (c/mL) at Week 48 using the FDA Snapshot algorithm \[Missing, Switch or Discontinuation = Failure (MSD=F)\] for the intent-to-treat exposed (ITT-E) population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Genetic barrier | 48 weeks | To assess the selection / emergence of viral resistance in subjects meeting confirmed virologic withdrawal (CVW) criteria. Endpoint: incidence of treatment-emergent genotypic resistance to DTG and 3TC or TDF/FTC in subjects meeting CVW criteria. |
| Efficacy in presence of any major resistanceassociated mutation al baseline | 48 weeks | To evaluate the antiviral activity of DTG + 3TC compared to DTG + TDF/FTC over time in patients with pre-existing viral resistance based on the presence of any major resistanceassociated mutation (IAS-USA 2019). Endpoint: Proportion of subjects with plasma HIV-1 RNA \<50 copies/mL (c/mL) at Week 48 using the FDA Snapshot algorithm and The proportion of participants with HIV-1 RNA \<50 or \<200 copies/mL using the observed algorithm (excluding participants with missing data) in patients with pre-existing viral resistance based on the presence of any major resistance-associated mutation (IAS-USA 2019). |
Countries
Argentina
Outcome results
None listed