Abstract Background Understanding HIV-1 reservoir dynamics during long-term antiretroviral therapy (ART) in youth with perinatal HIV-1 is essential for ART-free remission strategies. Methods 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. Results 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. Conclusions 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.
Khetan et al. (Mon,) studied this question.