The Journal of infectious diseases · 2026
Dynamics of Intact and Defective Human Immunodeficiency Virus Type 1 (HIV-1) Proviruses During Decades of Suppressive Antiretroviral Treatment in Young Adults With Perinatal HIV.
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Khetan Priya, Patel Kunjal, Yu Wendy, Szewczyk Joseph, Dhummakupt Adit, Burchett Sandra, Van Dyke Russell B, Persaud Deborah
Аннотация
BACKGROUND: Understanding HIV-1 reservoir dynamics during long-term antiretroviral therapy (ART) in youth with perinatal Human Immunodeficiency Virus Type-1 (HIV-1) is essential for ART-free remission strategies.
METHODS: We quantified intact and defective HIV 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.
RESULTS: Twenty-six participants (11 ES and 15 LS) were evaluated. Early-suppressed participants exhibited significantly lower intact HIV 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 infection results in substantially smaller HIV 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.
METHODS: We quantified intact and defective HIV 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.
RESULTS: Twenty-six participants (11 ES and 15 LS) were evaluated. Early-suppressed participants exhibited significantly lower intact HIV 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 infection results in substantially smaller HIV 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.