Virologic response to potent antiretroviral therapy and modeling of HIV dynamics in early pediatric infection
Department of Pediatrics; Program in Molecular Medicine
Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; HIV Infections; HIV-1; Humans; Infant; Infant, Newborn; RNA, Viral; Ritonavir; *Viral Load; Virus Replication
Immunology and Infectious Disease | Pediatrics
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.
DOI of Published Version
J Infect Dis. 2007 Jul 1;196(1):23-9. Epub 2007 May 24. Link to article on publisher's site
The Journal of infectious diseases
Palumbo P, Wu H, Chadwick EG, Ruan P, Luzuriaga K, Rodman J, Yogev R. (2007). Virologic response to potent antiretroviral therapy and modeling of HIV dynamics in early pediatric infection. Immunology/Infectious Disease. https://doi.org/10.1086/518508. Retrieved from https://escholarship.umassmed.edu/peds_immunology/55