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

Abstract

Immunogenicity; HIV-1 infection

Inmunogenicidad; Infección por VIH-1

Immunogenicitat; Infecció per VIH-1

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.

Special thanks to all the volunteers participating in this study, all the site investigators for their perseverance and dedication to the study, and Gilead study team members (Mary Wire, Cori Calabi, Donovan Verrill, Jamil Hussain, Felicity Blackburn, Andrea Knapp, and Gordon Strachan) for their support of the VES pharmacokinetic/pharmacodynamic analysis and the manuscript development. We thank Marie Pierre Malice of StatAdvice (Brussels) for statistical support. Editing and production assistance for the manuscript were provided by Parexel and funded by Gilead Sciences, Inc. This study was funded by AELIX Therapeutics and Gilead Sciences, Inc. J.M.M. received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017-2024. L.B. was supported by a PhD grant from the ISCIII Rio Hortega program (CM20/00097) during 2021–2023. The sponsors of the study, AELIX Therapeutics and Gilead Sciences, Inc., contributed to the study design, provided the treatments used in the study, oversaw all safety monitoring activities, data analysis, and interpretation, and provided a review of the manuscript.