Therapeutic HIV-1 Tat vaccination promotes durable immune reconstitution and reservoir reduction in ART-treated adults with clade C infection: a 12-year follow-up study

Abstract

Introduction: Antiretroviral therapy (ART) suppresses HIV replication but fails to eradicate viral reservoirs or fully restore immune competence. Therapeutic vaccination targeting HIV-1 Tat, a key viral protein persistently expressed also during ART, may enhance immune reconstitution and limit reservoir maintenance. Long-term data in individuals infected with HIV-1 clade C, particularly in sub-Saharan Africa, are lacking. Methods: T cells. Analyses were stratified by sex and ART adherence. Results: T-cell counts and continued reservoir reduction over time. Discussion: Therapeutic HIV-1 Tat vaccination induces long-lasting immunological benefits that extend beyond viral suppression achieved by ART alone, promoting durable immune reconstitution and progressive reservoir decay in clade C infection. These findings confirm results from a long-term follow-up of a parallel phase 2 trial in Italy, and both support Tat vaccination as a potential ART-intensifying strategy, particularly in populations with advanced immunosuppression or imperfect ART adherence. Trial registration: SANCTR n. DOH-27-0615-4948 and ClinicalTrials.gov: NCT02712489; and SANCTR n. DOH-27-072022-7347 and ClinicalTrials.gov: NCT05680948.