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

https://doi.org/10.1067/mpd.2002.125007Get rights and content

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 log10 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. (J Pediatr 2002;141:36-44)

Section snippets

Subject population

ART-experienced children 7 months to 10 years of age (n = 25) were enrolled in September 1997 at the Hospital del Niño in Panama City, Panama. All were participants in a double-blind, randomized, multicenter, placebo-controlled trial, simultaneously conducted in the United States and Panama, evaluating the safety and efficacy of the combination of ABC/3TC/ZDV versus 3TC/ZDV over a period of 48 weeks.25 A total of 26 children were enrolled at the Panama site in the multicenter study, and 25

Study population

All children were perinatally infected with HIV (Table I); 22 had been previously treated with ZDV and 1 with ddI, with duration of treatment ranging from 4 months to 3 years 2 months.

. Baseline characteristics of the study population

Empty CellABC/3TC/ZDV (n = 13)3TC/ZDV (n = 10)P value
Median age (y), (range)4 (0.58-10)4 (1-9).57
Median CD4% (range)12.60 (1.90-61.80)9.95 (1.60-23.50).42
Median CSF WBC count, cells/μL (range)7 (0-19)3 (0-12).16
Median CSF protein, mg/dL (range)35 (17-90)35.5 (18-65).51
Median

Discussion

In this study, CSF HIV RNA was measured longitudinally over 48 weeks after initiation of a new antiretroviral regimen with NRTIs to determine the long-term effectiveness on both CSF HIV RNA and neurologic function. The children enrolled in this substudy were not selected on the basis of the presence or absence of neurologic findings but rather on the basis of inclusion criteria from the multicenter study. The fact that 83% of the children enrolled were found to have neurologic abnormalities

Acknowledgements

We thank the children and their families for their participation in the study. We also thank Moisés Espino, MD (Hospital del Niño, Panama City, Panama), for his collaboration in the study and Jesús Saavedra, MD (UT Southwestern Medical Center, Dallas, Texas), for his review of the manuscript.

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    ☆

    Supported in part by a research grant from GlaxoWellcome Inc, Research Triangle Park, North Carolina.

    ☆☆

    Reprints not available from author. Please address correspondence to: Octavio Ramilo, MD, University of Texas Southwestern Medical Center, Department of Pediatrics, Room F3.202, 5323 Harry Hines Blvd, Dallas, TX 75390-9063.

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