Effect of combination antiretroviral therapy on cerebrospinal fluid HIV RNA, HIV resistance, and clinical manifestations of encephalopathy

J Pediatr. 2002 Jul;141(1):36-44. doi: 10.1067/mpd.2002.125007.

Abstract

Objectives: This study evaluated the effect of treatment with abacavir/lamivudine/zidovudine versus lamivudine/zidovudine on cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) RNA and clinical manifestations of HIV encephalopathy in children.

Study design: HIV-infected children 7 months to 10 years of age (n = 23) were studied. CSF and plasma were obtained at baseline and weeks 8, 16, and 48. Genotype analysis of HIV was attempted at baseline and week 48. Neurologic evaluations were performed at baseline and weeks 16, 32, and 48.

Results: At baseline, 83% of children had >2.00 log(10) copies/mL HIV RNA in CSF, but only 10% had HIV RNA measurable at week 48. Among children in whom paired genotyping of HIV was possible, 8 of 11 had identical patterns in both CSF and plasma at baseline, whereas at week 48, only 1 of 9 children had similar patterns. Neurologic abnormalities were observed in 83% of children at baseline but only 35% of children at week 48 (P =.004), suggesting a benefit of treatment.

Conclusions: Antiretroviral therapy was associated with a decline in CSF HIV RNA and an improvement in neurologic status. The development of genotypic mutations was different in CSF and plasma, suggesting discordant viral evolution. These results suggest that antiretroviral treatment in children should include agents with activity in the CNS.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / classification
  • AIDS Dementia Complex / diagnosis
  • AIDS Dementia Complex / drug therapy*
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Dideoxynucleosides / pharmacology
  • Dideoxynucleosides / therapeutic use*
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • HIV-1* / drug effects
  • HIV-1* / genetics
  • Humans
  • Infant
  • Lamivudine / pharmacology
  • Lamivudine / therapeutic use*
  • RNA, Viral / blood
  • RNA, Viral / cerebrospinal fluid
  • Statistics, Nonparametric
  • Viral Load
  • Zidovudine / pharmacology
  • Zidovudine / therapeutic use*

Substances

  • Anti-HIV Agents
  • Dideoxynucleosides
  • RNA, Viral
  • Lamivudine
  • Zidovudine
  • abacavir