PURPOSE OF THE STUDY.
US guidelines for initiating antiretroviral therapy (ART) for children with HIV infection suggest treatment in all patients younger than 12 months of age and for children older than 12 months of age depending upon immunologic (CD4 count) and virologic (plasma viral load) measures. The guidelines, therefore, assume that it is safe to delay therapy in some older children. However, poorer reconstitution of CD4 count has been demonstrated in pediatric patients who start ART at an older age and/or at lower CD4 counts. The purpose of this study is to describe the effects of age and pre-ART CD4 count on CD4 reconstitution with specific reference to the naïve T-cell population.
One hundred thirty perinatally HIV-infected, treatment-naïve, European children 3 months to 16 years of age were prospectively observed for a median of 5.7 years.
Subjects were randomly assigned to various treatment interventions. CD4 counts (z score modeled) and viral loads were recorded. Changes in naïve (CD4+, CD45RA+) and memory (CD4+, CD45RO+) subpopulations of T-cells were measured in a substudy of 26 patients.
One hundred twenty-seven patients started ART. Older patients had lower age-adjusted CD4 counts at the time of ART therapy initiation and long-term. At all ages, lower CD4 counts before therapy were associated with impaired CD4 recovery. Naïve CD4 counts increased comparably with overall CD4 counts. In a prediction model, a higher pretherapy CD4 score corresponded to a higher long-term T-cell score, and younger children had higher scores pretherapy and long-term.
The immune system of HIV-infected children, in contrast to that of adults, appears to be capable of efficient CD4 recovery through naïve T-cell population and expansion. This potential progressively decreases with duration of infection.
Current guidelines for starting children on ARV have been encumbered by the need to consider short- and long-term adverse effects of anti-HIV medications, and the difficulty of maintaining adherence to complex regimens containing unpalatable formulations of limited potency. As these obstructions are overcome, it is prudent to reconsider early initiation of ART with life-long maintenance. Of interest, this reviewer’s experience finds that children started on ART at younger than 1 year of age and adherent to their regimen are among the only patients who normalize their CD4:CD8 ratio. The relevance of this finding is yet to be clarified but suggests more effective immune reconstitution in children treated early in their course.
- Copyright © 2012 by the American Academy of Pediatrics