HIV-1-infection
Conditions
Brief summary
The purpose of this trial is to demonstrate at W48 the non-inferiority of a dual nucleoside analogues strategy with tenofovir (TDF) or tenofovir alafenamide (TAF) plus emtricitabine (FTC) or lamivudine (3TC) preceded by a 16 week induction period with TDF or TAF plus FTC or 3TC plus an integrase inhibitor (INI) relative to an immediate 2-DR strategy with dolutegravir plus 3TC in HIV-infected antiretroviral therapy (ARV) naïve participants with CD4 cells count greater than 300/mm3 and a low viral load defined as plasma HIV RNA strictly lower than 50 000 cp/mL
Detailed description
ANRS 173 ALTAR is a multicenter, comparative, international, open label, phase III randomized trial aiming at evaluating the non-inferiority of a TRI-BI (tritherapy-bitherapy) strategy (includes a 16 week - induction phase with 2 NRTI and a once daily integrase inhibitor followed by a bitherapy with TDF or TAF / XTC\*) in its capacity to achieve viral suppression at week 48 versus immediate BI (bitherapy) strategy (DTG/3TC) in participants naïve to antiretroviral therapy with plasma HIV RNA strictly less than 50 000 copies/mL and CD4 cells count above 300/mm3.
Interventions
DRUGAntiretroviral
Antiretroviral treatments (ART) will be allocated through central randomization (1:1:) according to the following two strategies: Tritherapy-Bitherapy (TRI-BI) strategy: TRI between D0 and W16: 3-drug combination (3-DR) including 2 NRTI (either TDF or TAF+XTC) and a once daily integrase inhibitor (Stribild® or Genvoya® or Biktarvy®) or TDF/XTC Gé + Tivicay® or TDF/XTC Gé + Isentress® QD 1200 mg when available) during 16 weeks BI between W16 and W96: if pVL viral load \<500 cp/mL at W4 and \<50 cp/mL at W12, participants will start the 2-DR regimen TDF or TAF / XTC (TDF/XTC Gé or Descovy®) at W16, until W96. (Descovy® : provided that it is available in France), (XTC = FTC or 3TC) Immediate Bitherapy (BI) strategy Dolutegravir (DTG, Tivicay® 50 mg QD) plus lamivudine (3TC, 300 mg QD) between D0 and W96. Antiretroviral drugs will be prescribed in the context of standard of care.
Sponsors
ANRS, Emerging Infectious Diseases
Institut National de la Santé Et de la Recherche Médicale, France
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
* Documented HIV-1 infection (positive HIV-1 serology or plasma viral load) * Age ≥ 18 years * Therapeutic antiretroviral treatment-naive participant (history of prophylaxy is accepted) * CD4 cells count \> 300 cells/mm3 at screening visit * HIV-1-RNA plasma viral load \<50 000 copies/mL at screening visit * Full susceptibility to trial drugs (NRTI, INI) at screening visit * eGFR (epidermal growth factor receptor) \> 60 mL /min (MDRD) * AST (aspartate aminotransferase), ALT(alanine transaminase) \< 3x norm * Absence of any AIDS-defining event and/or opportunistic infection * Possible contact by phone and/or email in order to be informed in case of detectable HIV plasma viral load * Negative urinary pregnancy test at screening visit for women of childbearing age * Written and informed consent signed * For French participants only: subject enrolled in or a beneficiary of a Social Security programme (including State Medical Aid (AME), only if Ethic Committee approves it)
Exclusion criteria
* HIV-2 co-infection * Hepatitis B Virus infection (positive HBs antigen) * Any comorbidity potentially related to a life expectancy below 12 months * Any condition (use of alcohol, drugs, etc.) judged by the investigator to possibly interfere with trial protocol compliance, adherence and/or trial treatment tolerance * Pregnant women or breastfeeding women * Women of childbearing age that do not want to use an effective method of contraception * Participant under justice protection * Galactose/lactose intolerance, Lapp lactase deficiency or glucose/galactose malabsorption (known or documented) * Participation to another clinical trial evaluating a new treatment/therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To demonstrate at W48 the non-inferiority | proportion of participants with plasma HIV-RNA <50 copies/mL at Week 48 in the 2 arms on allocated treatment (FDA snapshot approach) | To demonstrate at W48 the non-inferiority of a dual nucleoside analogues strategy with tenofovir (TDF) or tenofovir alafenamide (TAF) plus emtricitabine (FTC) or lamivudine (3TC) preceded by a induction period with TDF or TAF plus FTC or 3TC plus an integrase inhibitor (INI) relative to an immediate 2-DR strategy with dolutegravir plus 3TC in HIV-infected ART naïve participants with CD4 cells count greater than 300/mm3 and a low viral load defined as plasma HIV RNA strictly lower than 50 000 cp/mL |
Countries
France
Outcome results
None listed