Predictors of virological outcomes after analytical interruption of antiretroviral therapy and HTI vaccination in early treated people with HIV-1._.

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/106 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.