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
Lucía Bailón, José Moltó, Adrián Curran, Julen Cadiñanos, Juan Carlos López Bernaldo de Quirós, Ignacio de los Santos, Juan Ambrosioni, Arkaitz Imaz, Susana Benet, Paula Suanzes, Jordi Navarro, Juan González, Carmen Busca, Leire Pérez‐Latorre, Juan Berenguer, Lucio García‐Fraile, Gina Mejía‐Abril, José M Miró, Sofía Scévola, Santiago Moreno, Peré Domingo, Yuan Tian, Michelle Frankot, Daina Lim, Yanhui Cai, Elena Vendrame, Susan Guo, Jeffrey J. Wallin, Romas Geleziunas, Devi SenGupta, Yovaninna Alarcón‐Soto, Isabel Leal, Alvaro Aranguen, Margarida Garcia-Garcia, Ian McGowan, Christian Brander, José Ramón Arribas, Beatriz Mothe, On behalf of the AELIX-003 Study Group, Ignacio de los Santos, Patricia Cobarsí, Cristina Martínez, Aroa Nieto, Francisco A. Perez, Jordi Puig, Samandhy Cedeño, Bonaventura Clotet, Eulàlia Grau, Anuska Llano, Roger Paredes, J. Cabero, Jordi Naval, Vicenç Falcó, Bibiana Planas, Joaquín Burgos, María J. Buzón, Meritxell Genescà, Judith Grau-Expósito, Alberto M. Borobia, Víctor Hontañón, Javier Queiruga, Rafael Micán, Enrique Seco, Cristina Díez, Paloma Gijón, Margarita Ramírez, Samuel Martín‐Vílchez, Alejandro de Miguel‐Cáceres, J. M. Serra, Tamara De la Torre-Muñoz, Eva Ariza, Anna Ferrer, Benito García, Sandra Morenilla, Jordí Niubó, Camila Piatti, Irene Soriano, Daniel Vázquez
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. 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.