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.
Palumbo
Paul
P
Department of Pediatrics, University of Medicine and Dentistry-New Jersey Medical School, Newark, NJ, USA. paul.palumbo@dartmouth.edu
Wu
Hulin
H
Chadwick
Ellen
E
Ruan
Ping
P
Luzuriaga
Katherine
K
Rodman
John
J
Yogev
Ram
R
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019438:Ritonavir