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).
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.
Currently pregnant or breastfeeding or planning to become pregnant during study participation.
Prior receipt of anti-HIV broadly neutralizing antibody therapy.
Receipt of any non-HIV monoclonal antibody therapy within 1 year prior to study entry.
Prior receipt of a latency-reversing agent (LRA).
Parallel
ChAdOx1.tHIVconsv1
Biological/VaccineAdministered as 0.4 mL intramuscularly (IM) at Week 0
ChAdOx1.HIVconsv62
Biological/VaccineAdministered as 0.3 mL IM at Week 0
MVA.tHIVconsv3
Biological/VaccineAdministered as 0.3 mL IM at Week 4
MVA.tHIVconsv4
Biological/VaccineAdministered as 0.5 mL IM at week 4
Vesatolimod (VES)
DrugVES 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.
GS-5423
DrugAdministered via intravenous (IV) infusion at week 7
GS-2872
DrugAdministered via IV infusion at week 7
MVA.tHIVconsv4
Biological/VaccineAdministered 0.5 mL IM at week 60
Placebo
Biological/VaccinePlacebos for vaccines, VES, and bnAbs
Occurrence of any serious adverse event (AE), Grade 3 or higher AE, or AE that leads to permanent discontinuation of study treatment regardless of grade, that is related to ChAdOx1-MVA/HIVconsvX vaccines, vesatolimod, GS-5423 or GS-2872
Proportion of participants with viral control during an ATI defined as remaining off ART with HIV-1 RNA <1,000 copies/mL at Week 16 following ATI.
Change in cell-associated HIV-1 RNA and DNA levels
Change in plasma HIV-1 RNA viral load as measured by single copy assay (SCA)
Change in intact proviral DNA levels (IPDA)
HIV-1-specific T-cell responses to the conserved regions present in the vaccines as measured by IFN-γ ELISPOT - total frequency and breadth (number of recognized peptide pools out of 10).
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National Institute of Allergy and Infectious Diseases (NIAID)
Lead sponsor
University of Oxford
Collaborator
Gilead Sciences
Collaborator
