Share Abstract
T-cell responses induced by HTI vaccines and vesatolimod correlate with improved control of HIV rebound
Abstract Content:
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 IFNγ 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.
METHODS: Longitudinal changes in HTI-specific T-cell responses were measured by IFNγ 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.