Dynamics of Intact and Defective HIV-1 Proviruses during Decades of Suppressive Antiretroviral Treatment in Young Adults with Perinatal HIV-1.

Abstract

Understanding HIV-1 reservoir dynamics during long-term antiretroviral therapy (ART) in youth with perinatal HIV-1 is essential for ART-free remission strategies. We quantified intact and defective HIV-1 proviruses in 201 peripheral blood mononuclear cell samples (PBMCs) from participants ages 17.6-21.2 years in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol. Participants were classified as early-suppressed (ES, <1 year of age at virologic suppression (VS)) or late-suppressed (LS, 1-5 years of age at VS) and had maintained VS for up to 20 years. We compared proviral dynamics based on age at and duration of suppression, and sex. Twenty-six participants (11 ES and 15 LS) were evaluated. ES participants exhibited significantly lower intact HIV-1 reservoirs compared with LS participants, with 67% of ES samples below detection limits (2.0 copies/106 PBMCs), By 5 years of VS, the ES participants had significantly lower mean intact proviral load (2.0 vs 6.6 copies/106 PBMCs) than LS participants, largely driven by faster clearance of intact proviruses in the first 5 years of VS. Among LS- participants, females had larger intact reservoirs than males (mean: 12.5 vs 4.1 intact copies/106 PBMCs) and exhibited greater increases in defective proviruses over time. Achieving VS by 1 year of age in perinatal HIV-1 infection results in substantially smaller HIV-1 intact reservoirs by age 5, with effects sustained through young adulthood. Additionally, sex-based differences, larger intact reservoirs and increases in defective proviruses in females, underscore the need for tailored ART-free remission and cure strategies for this population.