Age at ART initiation and proviral reservoir size in perinatal HIV-1 infection: considerations for ART-free remission

Achieving ART-free remission without the need for lifelong antiretroviral treatment (ART) is a new objective in HIV-1 therapeutics. This review comprehensively examines the literature to evaluate whether the age at ART initiation in children with perinatal HIV-1 influences the size and decay of the HIV-1 reservoir. The insights gathered from this review serve to inform the field on the unique dynamics of HIV-1 reservoir size in perinatal HIV-1 infection as a function of age at ART initiation, as well as inform biomarker profiling and timing of ART-free remission strategies for children living with HIV-1 globally.

Recent studies demonstrate that initiating very early effective ART in neonates is feasible and limits HIV-1 reservoir size. The clinical relevance of limiting the HIV-1 reservoir size in perinatal infection was recently demonstrated in the Tatelo Study, which investigated a treatment switch from ART to two broadly neutralizing antibodies (bNAbs) in very early treated children. Low proviral reservoir size was associated with sustained virologic control for 24 weeks on bNAbs.

Immediate and early ART initiation for neonates and infants with perinatal HIV-1 is essential to restricting HIV-1 reservoir size that may enable ART-free remission.