Abstract
BACKGROUND: Randomized, placebo-controlled clinical trials (RCTs) that include analytical treatment interruptions (ATI) are conducted to test the efficacy of HIV cure strategies. Two independent RCTs, AELIX-002 and AELIX-003, evaluated the HTI immunogen-based vaccines alone or combined with the TLR7 agonist vesatolimod in early-treated people with HIV (etPWH). These studies individually demonstrated that higher levels of vaccine-induced HTI-specific T-cell responses were associated with extended time off antiretroviral therapy (ART) during a 24-week ATI. METHODS: We conducted a pooled analysis of both RCTs including the individual data of a total of 88 participants. The association between clinical, immunogenicity and viral data and rebound outcomes during the ATI was evaluated using logistic regression and receiver operating characteristic (ROC) analyses. RESULTS: We identify an HTI-specific threshold of 835 spot-forming cells/10(6) peripheral blood mononuclear cells as a predictor of delayed and slower viral rebound during ATI. This threshold distinguishes participants who remain off ART for >12 weeks, with 58% sensitivity, 85% specificity, 75% positive and 73% negative predictive value. CONCLUSIONS: These findings confirm that HTI-specific T-cell magnitude at ATI initiation is the strongest predictor of ATI outcomes observed in AELIX002/003 studies and that a threshold of vaccine-induced HTI-specific T-cell responses can be used as futility criteria before ATI and/or guide participant selection in future HTI-based HIV cure trials aimed at achieving therapy-free remission.