Journal Article

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

SenGupta, Devi, de Los Santos, Ignacio, Ambrosioni, Juan, Suanzes, Paula, Mejía-Abril, Gina, Imaz, Arkaitz, Vendrame, Elena, García-Fraile, Lucio Jesús, Geleziunas, Romas, Domingo, Pere, Brander, Christian, Berenguer, Juan, Garcia-Garcia, Margarida, Miró, Jose M., Guo, Susan, Arribas, Jose Ramón, Pérez-Latorre, Leire, Moltó, José, Wallin, Jeffrey J., Mothe, Beatriz, McGowan, Ian, Curran, Adrian, Lim, Daina, Alarcón-Soto, Yovaninna, Bailón, Lucia, Navarro, Jordi, Scévola, Sofía, Cai, Yanhui, Busca, Carmen, Benet, Susana, Tian, Yuan, Leal, Isabel, Moreno, Santiago, Aranguen, Alvaro, Cadiñanos, Julen, Frankot, Michelle, Carlos Lopez Bernaldo de Quirós, Juan, González-García, Juan

2025

Overview

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. Here the authors report results from a randomized clinical trial testing a combination of ChAOx1/MVA.HTI vaccines and the TLR7 agonist vesatolimod in men living with HIV-1. While the treatment showed a good safety profile and induction of HTI-focused T-cell responses, viral rebound was similar in treatment arm and placebo arm.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 692/308/153 / 692/308/2779/777 / 692/699/255/1901 / Adult / Agonists / AIDS Vaccines - administration & dosage / AIDS Vaccines - adverse effects / AIDS Vaccines - immunology / Antiretroviral agents / Antiretroviral drugs / Antiretroviral therapy / Clinical trials / Combined vaccines / Double-Blind Method / Drug therapy / Headache / HIV / HIV Infections - drug therapy / HIV Infections - immunology / HIV Infections - therapy / HIV Infections - virology / HIV-1 - drug effects / HIV-1 - immunology / Human immunodeficiency virus / Humanities and Social Sciences / Humans / Immunogenicity / Immunogenicity, Vaccine / Lymphocytes / Lymphocytes T / Male / Middle Aged / multidisciplinary / Placebos / Pteridines / Public health / Safety / Science / Science (multidisciplinary) / TLR7 protein / Toll-Like Receptor 7 - agonists / Toll-like receptors / Vaccines / Viral Load - drug effects