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.
Keywords: HIV; early suppression; perinatal; proviral; reservoir; young adults.
This study looked at how the amount of intact HIV, also known as the HIV reservoir, changes over time in young people with perinatal HIV and have been taking antiretroviral treatment for many years. When a person first acquires HIV, the virus forms a reservoir in long-lived CD4+ memory T cells, which allows HIV to rebound if antiretroviral treatment is stopped. We analyzed blood samples from 26 young adults who were enrolled in a long term study of pediatric HIV. We compared the size of the HIV reservoir in individuals who suppressed their HIV from early infancy with those who achieved viral suppression in later childhood. We found that after 5 years, young adults who started treatment early in life had much smaller amounts of intact HIV than those treated later. Among the participants who achieved viral suppression later, we also observed differences between males and females: females had larger HIV reservoirs. Overall, our findings show that starting HIV treatment in early life can significantly reduce the size of the HIV reservoir, and highlight important sex-based differences in HIV persistence. These insights point to the need for personalized approaches in future efforts to achieve an HIV cure.
© The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America.