Predictors of virological outcomes after analytical interruption of antiretroviral therapy following immune interventions with HTI vaccines in early-treated people with HIV: a pooled analysis from the AELIX-002 and AELIX-003 clinical trials

Randomized, placebo-controlled clinical trials (RCTs) incorporating analytical treatment interruptions (ATI) are the gold standard in HIV cure research. Two independent RCTs, AELIX-002 and AELIX-003, evaluated HTI immunogen-based vaccines alone or combined with the TLR7 agonist vesatolimod in 88 early-treated people with HIV. These trials individually demonstrated that higher levels of vaccine-induced HTI-specific T-cell responses were associated with extended time off antiretroviral therapy (ART). Here, we performed a pooled analyses of both RCTs using logistic regression and receiver operating characteristic analyses and identified an HTI-specific cutoff of 835 spot-forming cells/10(6) peripheral blood mononuclear cells as a predictor of delayed and slower viral rebound during ATI. This threshold distinguished participants who are likely to remain off ART for >12 weeks, with 58% sensitivity, 85% specificity, 75% positive predictive value and 73% negative predictive value. These findings may inform futility criteria before ATI start in future HTI-based trials.