Safety, immunogenicity and effect on viral rebound of HTI vaccines combined with a TLR7 agonist in early-treated HIV-1 infection: a randomized, placebo-controlled phase 2a trial

Nat Commun. 2025 Mar 4;16(1):2146. doi: 10.1038/s41467-025-57284-w.

Abstract

Building on results from the AELIX-002 trial with HIVACAT T-cell immunogen (HTI)-based vaccines, the AELIX-003 (NCT04364035) trial tested the safety of the combination of ChAdOx1.HTI (C) and MVA.HTI (M), with the TLR7 agonist vesatolimod (VES), in a double-blind, placebo-controlled, randomized clinical trial in 50 virally suppressed early-treated men with HIV-1 infection. Secondary objectives included immunogenicity and effects on viral rebound kinetics during a 24-week antiretroviral treatment interruption (ATI). The most common treatment-related adverse events were mild-to-moderate injection-site pain, influenza-like illness, headache, and fatigue. Strong, broad, and HTI-focused T-cell responses were induced by vaccination. All participants experienced viral rebound in ATI; 33.3% and 23.5% (P = 0.4494) of CCMM + VES and placebo recipients, respectively, remained off antiretroviral therapy for 24 weeks. Post hoc analysis confirmed a correlation between levels of HTI-specific T cells and prolonged time off antiretroviral therapy. The combination of HTI vaccines and VES was safe and elicited robust T-cell responses.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II

MeSH terms

  • AIDS Vaccines* / administration & dosage
  • AIDS Vaccines* / adverse effects
  • AIDS Vaccines* / immunology
  • Adult
  • Double-Blind Method
  • HIV Infections* / drug therapy
  • HIV Infections* / immunology
  • HIV Infections* / therapy
  • HIV Infections* / virology
  • HIV-1* / drug effects
  • HIV-1* / immunology
  • Humans
  • Immunogenicity, Vaccine
  • Male
  • Middle Aged
  • Pteridines
  • Toll-Like Receptor 7* / agonists
  • Viral Load / drug effects

Substances

  • Toll-Like Receptor 7
  • AIDS Vaccines
  • TLR7 protein, human
  • vesatolimod
  • Pteridines