Significant advances in the field of HIV-1 therapeutics to achieve antiretroviral treatment (ART)-free remission and cure for persons living with HIV-1 are being made with the advent of broadly neutralizing antibodies and very early ART in perinatal infection. The need for HIV-1 remission and cure arises due to the inability of ART to eradicate the major reservoir for HIV-1 in resting memory CD4+ T cells (the latent reservoir), and the strict adherence to lifelong treatment. To measure the efficacy of these cure interventions on reservoir size and to dissect reservoir dynamics, assays that are sensitive and specific to intact proviruses are critical. In this review, we provided a broad overview of some of the key interventions underway to purge the reservoir in adults living with HIV-1 and ones under study in pediatric populations to reduce and control the latent reservoir, primarily focusing on very early treatment in combination with broadly neutralizing antibodies. We also summarized assays currently in use to measure HIV-1 reservoirs and their feasibility and considerations for studies in children.

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.