The A5374 trial is a randomized, two-arm, double-blind, placebo-controlled, multi-stage phase I/IIa strategy trial to evaluate the safety and efficacy of therapeutic vaccination with chimpanzee adenovirus (ChAdV) vectored conserved mosaic T-cell vaccines and Ankara vaccinia (MVA) modified poxviruses in a sequential regimen with Toll-like Receptor 7 (TLR7) agonist vesatolimod (VES) and two broad-spectrum neutralizing antibodies (bNAbs) of the CD4 binding site and V3 loop base classes in HIV-1 individuals who initiated suppressive antiretroviral therapy (ART) during acute HIV-1. Participants will be screened for eligibility and will have a pre-entry visit.

After eligibility is determined, participants will be randomized prior to entry to the active intervention arm (Arm A) or the placebo arm (Arm B) in a 2:1 ratio. The study consists of four stages, including an analytical treatment interruption (IAT).

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• STAGE 1: Study Intervention and ART (67 weeks)

• STAGE 2: Analytical Treatment Interruption (up to 24 weeks)

• STAGE 3: ART Resumption (24 weeks)

• STAGE 4: IAT Continuation (up to 24 weeks)

Each participant will complete Stage 1 and Stage 2. At the end of Stage 2, participants who have experienced virological relapse will enter Stage 3 and resume ART. Participants with continuous virological control for 24 weeks in Stage 2 will enter Stage 4 for an extended IAT. Each participant will be enrolled for up to approximately 110 weeks. The total study time for each participant depends on the time spent in the treatment interruption stages (Stages 2 and 4).