Background
The persistence of the HIV-1 reservoir requires lifelong combination antiretroviral therapy (cART). A therapeutic vaccine able to control the virus could limit disease progression and transmission. The HIV-CORE 007 trial evaluated the safety, immunogenicity, and, for the first time, post-treatment virological control of ChAdOx1- and MVA-vectored vaccines expressing conserved HIV-1 mosaic regions (HIVconsvX) in early-treated adults living with HIV-1 in Milan, Italy.
Methods
HIV-CORE 007 is a phase I/II, randomized, placebo-controlled, single-blind clinical trial (EudraCT 2019-003102-26, funded by Ministero della Salute, GR-2018-12367076)). Participants started cART during primary infection and maintained viremia <20 cp/ml for at least 2 years. Thirty-three were planned, but 11 were enrolled and randomized 2:1 to receive either prime-boost vaccination ChAdOx1.tHIVconsv1 (C1) at week 0, followed by MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) at week 4 (regimen C1-M3M4) or placebo (saline), via intramuscular injection. At week 12, participants were unblinded and offered an analytical treatment interruption (ATI). Safety monitoring included local and systemic recording of adverse events (AE), and laboratory evaluations. Exploratory objectives were assessed by IFN-γ ELISPOT, HIV-DNA quantification, and HLA/KIR genotyping.
Results
Vaccination was well tolerated: all recipients experienced expected mild-to-moderate local or systemic reactions (pain, fever, myalgia, malaise). Two grade 3 AEs (elevated creatine phosphokinase; nasal congestion with epistaxis) occurred but were unrelated to the vaccines; no serious AEs were reported. Viral suppression and stable CD4/CD8 counts were maintained. All 7 vaccinees developed HIV-1-specific T-cell responses to HIVconsvX (IN pools), whereas responses to non-vaccine regions (OUT pools) varied, reflecting individual immune competence. Placebo recipients showed no new or enhanced responses. All vaccinated participants accepted ATI and all placebo recipients declined. Viral rebound occurred 5–11 weeks after cART cessation, with stable CD4 counts and no acute retroviral syndrome; cART was safely reintroduced per protocol.
Conclusions
HIV-CORE 007 demonstrates that the C1-M3M4 vaccination is safe and immunogenic in people living with HIV-1. Despite limited recruitment and ATI challenges, the data support further development of T cell-based therapeutic vaccines and help define correlates of post-treatment viral control.