Phase II Trial of ART + Dual bNAbs vs. ART + Placebo During Primary HIV-1 Infection-impact on Post-ART Control

A Randomised Phase II Placebo-controlled Trial of Antiretroviral Therapy (ART) Plus Dual Long-acting HIV-specific Broadly Neutralising Antibodies (bNAbs) vs ART Plus Placebo During Primary HIV-1 Infection to Study the Impact on Post-treatment HIV Control.

RHIVIERA-02 trial is a placebo-controlled double-blinded two arm prospective phase II trial. This study will test the use of broadly neutralising antibodies (bNAbs) in participants, at primary HIV infection (PHI) and ART initiation.

The study proposes to test an intervention consisting of dual long-acting HIV-specific broadly neutralizing antibodies (3BNC117-LS & 10-1074-LS ) + ART, at primary HIV-1 infection, and to compare it to ART only regarding HIV-1 replication.

The study aims to enrol 69 participants in French (Ile-de-France) clinical centres. Participants will have been diagnosed with primary HIV-1 infection, will start ART during early phase of Primary HIV infection, and will interrupt ART 52 weeks later.

Study duration will vary by participant, depending on the time of ART interruption and the time to viral rebound.

Inclusion Criteria:

• Confirmed primary HIV-1 infection diagnostic
• Aged ≥18 to ≤70 years old at screening
• Willing to use use an effective method of contraception from the inclusion until the end of the follow-up in the trial
• Negative plasmatic beta human chorionic gonadotropin (β-HCG) pregnancy test, when applicable
• Agree not to seek pregnancy including through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit, when applicable
• Informed and written signed consent
• Participant with regular health insurance
• Willing to accept the trial constraints (travel for IMP administration and ART interruption)
• Willing to be vaccinated against COVID-19 according to recommandations

Exclusion Criteria:

• Participation in any other clinical trial requiring additional blood sampling Participation in an observational study without additional blood sampling is permitted
• Participants in whom condom use or PrEP use by the partner will be difficult or impossible
• Pregnant or breastfeeding patient
• Participants under guardianship or curatorship
• Any condition or infection, including HCV, HBV, SARS-CoV-2 or known M. tuberculosis active infection History of ischemic heart disease (myocardial infarction, stable or unstable angina, stroke)
• Current or past history of cancer, excluding squamous cell skin cancers
• History or acute known inflammatory ophthalmic affection (uveitis, choroiditis, optic neuropathy)
• Any medical condition that contraindicates ART interruption
• Concomitant or previous conditions that preclude injection of monoclonal antibodies
• History of systemic corticosteroids, immunosuppressive and anti-cancer medications within the last 6 months
• History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions
• Individuals with any contraindication (including hypersensitivity reaction) to 3BNC117-LS and 10-1074-LS infusion
• Prothrombin < 50%
• Creatinine clearance < 60mL/mn (Cockroft)
• ASAT or ALAT or bilirubine (total et conjugated) ≥ 10 times the upper limit of normal
• Patient with an isolated HIV-2 viral strain
• Planned absence that could affect participation in the trial (travel abroad, relocation, impending transfer...)