National Institute of Allergy and Infectious Diseases (NIAID)
The purpose of this study is to evaluate the safety, tolerability, and efficacy of therapeutic vaccination with chimpanzee adenovirus ChAdOx1- and poxvirus modified vaccinia Ankara (MVA)-vectored conserved mosaic T-cell vaccines in a sequential regimen with the toll-like receptor 7 (TLR7) agonist vesatolimod (VES) and two broadly neutralizing antibodies (bNAbs) compared to placebo, to induce HIV-1 control during analytic treatment interruption (ATI).
A5374 is a phase I/IIa randomized, two-arm, double-blind placebo-controlled, multi-step strategy trial to evaluate safety and efficacy of therapeutic vaccination with chimpanzee adenovirus ChAdOx1- and poxvirus modified vaccinia Ankara (MVA)-vectored conserved mosaic T-cell vaccines in a sequential regimen with the toll-like receptor 7 (TLR7) agonist vesatolimod (VES) and two broadly neutralizing antibodies (bNAbs) of the CD4 binding site and V3-loop base classes in individuals with HIV-1 who started suppressive antiretroviral therapy (ART) during acute HIV-1. Participants will be screened fo…
Inclusion Criteria * Provision of written informed consent. * History of Initiation of combination ART within 90 days of acute HIV diagnosis * On ART for at least 12 months with no known ART interruption \>28 consecutive days within 12 months prior to Step 1 Study Entry * ART with an integrase inhibitor-based regimen with two NRTIs or dolutegravir/lamivudine regimen for at least 6 weeks prior to Study Entry. * Willingness to participate in the ATI and willingness to restart ART according to study guidelines. * Willingness to adhere to protocol therapy and complete all study visits. * Weight ≥…
Administered as 0.4 mL intramuscularly (IM) at Week 0
Administered as 0.3 mL IM at Week 0
Administered as 0.3 mL IM at Week 4
Administered as 0.5 mL IM at week 4
VES 6 mg administered orally once every 2 weeks for two doses, then VES 8 mg once every 2 weeks for 8 doses. Dose escalation may be held or the 8 mg dose may be reduced for intolerability for weeks 6 through 24.
Administered via intravenous (IV) infusion at week 7
Administered via IV infusion at week 7
Administered 0.5 mL IM at week 60
Placebos for vaccines, VES, and bnAbs