Background:
In early-treated people with HIV (PWH), the HIV-specific T cell response induced by a combination of DNA.HTI (D), MVA.HTI (M) and ChAdOx1.HTI (C) vaccines was associated with longer time off antiretroviral therapy (ART) during analytical treatment interruption (ATI) (AELIX-002; Bailón L et al. Nat Med 2022). AELIX-003 (NCT04364035) was a double-blind, randomized (2:1), multi-center trial, to evaluate the safety, immunogenicity and efficacy of CCMM and the TLR7 agonist vesatolimod (VES) in early-treated PWH.
Methods:
PWH who started ART within 6 months of infection and had been suppressed on ART for at least one year were randomized 2:1 to receive vaccines and 10 doses of oral vesatolimod 6 mg or placebo while continuing ART (Fig 1). During a 24-week ATI, ART was resumed if plasma viral load >100,000 c/mL, or >10,000 c/mL for 8 weeks, and/or CD4 < 350 cells/µL. INFg ELISpot on cryopreserved PBMC, SIMOA, multiplex cytokine and intact proviral HIV DNA assays were used to evaluate immunogenicity, VES pharmacodynamic (PD) biomarkers and changes in viral reservoir, respectively.
Results:
50 participants were enrolled and 47 entered the ATI (CCMM+VES [n=30] or placebo [n=17]). The intervention was well-tolerated with 1 unrelated SAE. Currently available immune data from 31/47 (66%) participants demonstrated strong immunogenicity. The total peak HTI-specific T cell response increased from baseline in the active arm, with median (range) increase of 2474 spot-forming cells (SFC)/106 PMBC (635 to 9310) vs. 610 SFC/106 PMBC (50 to 3645) in the placebo arm, respectively (p=0.001). Compared to AELIX-002, where HTI vaccines were given alone as DDDMM followed by CCM, peak total HTI-specific responses in AELIX-003 were significantly higher (p=0.027). At time of ATI start, a median (range) of 52% (13% to 100%) of the total anti-HIV-1 T-cell response was HTI-specific in the active arm vs 19% (0% to 100%) in the placebo arm (p=0.01). VES increased the production of antiviral cytokines (IFN-a, IL1RA) and chemokines (ITAC) 24h post-dosing. Decay in total and intact HIV proviral DNA from baseline to ATI was similar between arms. Ten out of 30 (33%) participants in the active arm remained off ART for 24 weeks compared to 24% (4/17) in the placebo arm.
Conclusions:
In early-treated PWH, HTI vaccines and VES were safe and induced stronger HTI responses than the more complex AELIX-002 vaccine regimen. Mechanism of action and viral outcome correlate analyses are ongoing.
Figure 1 AELIX-003 study design