Timing Is Everything: Reservoir Dynamics and Immune Correlates in Perinatally Acquired HIV-1 Across the Lifespan

Purpose of Review This review synthesizes the past 5 years of research on individuals with perinatally acquired HIV-1 (PHIV) with a focus on evaluating the proviral reservoir landscape and associated immunological correlates. Recent Findings We found that the age at the time of study shapes the questions being addressed and insights gained from infancy through adulthood in PHIV cohorts where ART timing shapes immune development and reservoir establishment. In infants and newborns, there has been more frequent antiretroviral therapy interruption (ATI) studies, with and without immunotherapy (e.g., bNAbs), aiming to replicate Mississippi Baby-like control in early-treated infants with small reservoirs. In long-term suppressed adolescents and adults with PHIV, work increasingly focuses on characterization of the long-lived HIV-1 reservoir and defining immunological correlates of smaller, less diverse reservoirs in order to predict post-treatment control. Summary Understanding perinatal HIV-1 infection by life stage is essential for guiding future intervention and cure research.