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Title
T-cell responses induced by HTI vaccines and vesatolimod correlate with improved control of HIV rebound
Presenter
Beatriz Mothe
Authors
B. Mothe1, L. Bailon2, A. Curran3, J.C. Lopez4, J. Cadinanos5, I. De Losa Santos Gil6, J. Ambrosioni7, A. Imaz8, Y. Alarcon-Soto9, D. SenGupta10, R. Geleziunas10, J. Cai10, M. Frankot10, E. Vendrame10, I. McGowan11, C. Brander11, J.R. Arribas12
Institutions
1IrsiCaixa AIDS Research Institute, HUGTiP, CIBERINFEC, Infectious Diseases Department, Barcelona, Spain, 2Fight Infections Foundation, HUGTiP, UAB, Barcelona, Spain, 3Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca, Barcelona, Spain, 4Hospital General Universitario Gregorio Marañon, CIBERINFEC, Madrid, Spain, 5Hospital Universitario La Paz, CIBERINFEC, Madrid, Spain, 6Hospital Universitario de La Princesa, CIBERINFEC, Madrid, Spain, 7Hospital Clinic de Barcelona, Barcelona, Spain, 8Hospital Universitari de Bellvitge, Institut d'Investigaci Biomèdica de Bellvitge (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain, 9Fight Infections Foundation, HUGTiP, Barcelona, Spain, 10Gilead Sciences, Inc., Foster City, United States, 11AELIX Therapeutics, Barcelona, Spain, 12Hospital Universitario La Paz & IdiPaz, CIBERINFEC, Madrid, Spain

BACKGROUND: Vaccination with HIV-specific T-cell immunogens is a key component of a potential HIV cure strategy. The HIVACAT T-cell immunogen (HTI) redirects cellular immune responses to HIV targets associated with viral control and is currently expressed in DNA (D), ChAdOx1 (C), and MVA (M) viral vectors. AELIX-002 (NCT03204617) and AELIX-003 (NCT04364035) were randomized (2:1), placebo-controlled studies in early-treated people with HIV (PWH) of HTI vaccines given alone (DDDMM followed by CCM) or in combination with the toll-like receptor 7 agonist vesatolimod (CCMM+VES), respectively. Here, we report AELIX-003 final immunogenicity results, and AELIX-002/AELIX-003 pooled analyses of immune correlates of virological outcomes after a 24-week analytical treatment interruption (ATI).
METHODS: Longitudinal changes in HTI-specific T-cell responses were measured by IFN? EliSPOT up to ATI start. During ATI, plasma viral load (pVL) was monitored weekly and antiretroviral treatment (ART) was resumed if pVL >100,000 copies/mL and/or >10,000 copies/mL for 8 consecutive weeks. Study populations and immunogenicity at ATI start were compared between studies. A pooled survival analysis of efficacy outcomes was undertaken using the Gehan-Breslow-Wilcoxon test.
RESULTS: Median (range) of peak total HTI-specific T-cell responses in the CCMM+VES (n=31) and placebo (n=16) arms were 1710 (0-4790) and 413 (0-1460) spot-forming cells/106 peripheral blood mononuclear cells, respectively (P<0.0001, van Elteren test with stratification for beneficial HLA alleles). Similar to AELIX-002, total HTI-specific T-cell responses at ATI start were significantly correlated with longer time to ART resumption (R=0.49, P=0.01) in the CCMM+VES but not in the placebo arm. Study populations were comparable between AELIX-002 and AELIX-003, and levels of vaccine-induced HTI-specific T-cell responses at ATI start were not statistically different. In the survival analysis, participants with HTI-specific responses above the median magnitude of the pooled populations (n=84) at ATI start had a significantly delayed (time to pVL >50 copies/mL) and slower (time to pVL >10,000 copies/mL) viral rebound, and an increased time off ART versus individuals with below the median responses (P<0.05 for all).
CONCLUSIONS: HTI vaccines are highly immunogenic in early-treated PWH. AELIX-003 confirmed previous clinical findings demonstrating that vaccine-induced HTI-specific T-cell responses contribute to improved control of HIV viremia after ATI.

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