Virologic response to potent antiretroviral therapy and modeling of HIV dynamics in early pediatric infection

BACKGROUND: Human immunodeficiency virus (HIV) infection in infancy features a persistently high viral load and elevated antiretroviral drug clearance rates, which pose significant therapeutic challenges to the clinician. Viral and cellular kinetic analyses performed in HIV-infected adults have yielded significant insights into the dynamic setting of this viral infection. Similar studies are needed in pediatric populations, in whom differing dynamics might translate into age-specific treatment approaches. METHODS: Viral and cellular kinetic analyses were performed using a nonlinear mixed-effects model in a cohort of 48 infants 1-24 months of age enrolled in a trial of ritonavir-based highly active antiretroviral therapy (HAART). RESULTS: Infected cell compartment kinetics were comparable with reported adult values, with no age-specific differences demonstrated--suggesting the ability to suppress viral replication in infants receiving HAART. Comparisons between 2 ritonavir dosing schedules revealed significant improvement in phase 1/2 decay constants in favor of the higher dose. A negative correlation was established between plasma RNA levels and phase 1 decay rates, which has worrisome implications for infant therapeutics given high infant pretreatment plasma virus levels. CONCLUSIONS: Ritonavir-based HAART regimens in infancy result in HIV decay constants comparable to those reported in adults, without age-specific variability. Despite higher plasma HIV levels and CD4 lymphocyte counts in infancy, HAART can result in timely, effective control of viral replication