Using CD4 percentage and age to optimize pediatric antiretroviral therapy initiation

Pediatrics. 2014 Oct;134(4):e1104-16. doi: 10.1542/peds.2014-0527.

Abstract

Background: Quantifying pediatric immunologic recovery by highly active antiretroviral therapy (HAART) initiation at different CD4 percentage (CD4%) and age thresholds may inform decisions about timing of treatment initiation.

Methods: HIV-1-infected, HAART-naive children in Europe and the Americas were followed from 2002 through 2009 in PENPACT-1. Data from 162 vertically infected children, with at least World Health Organization "mild" immunosuppression and CD4% <10th percentile, were analyzed for improvement to a normal CD4% (≥10th percentile) within 4 years after HAART initiation. Data from 209 vertically infected children, regardless of immune status, were analyzed for CD4% outcomes at 4 years and viral failure within 4 years.

Results: Seventy-two percent of baseline immunosuppressed children recovered to normal within 4 years. Compared with "severe" immunosuppression, more children with "mild" immunosuppression (difference 36%, 95% confidence interval [CI]: 22% to 49%) or "advanced" immunosuppression (difference 20.8%, 95% CI: 5.8% to 35.9%) recovered a normal CD4%. For each 5-year increase in baseline age, the proportion of children achieving a normal CD4% declined by 19% (95% CI: 11% to 27%). Combining baseline CD4% and age effects resulted in >90% recovery when initiating HAART with "mild" immunosuppression at any age or "advanced" immunosuppression at age <3 years. Baseline CD4% effects became greater with increasing age (P = .02). At 4 years, most immunologic benefits were still significant but diminished. Viral failure was highest in infancy (56%) and adolescence (63%).

Conclusions: Initiating HAART at higher CD4% and younger ages maximizes potential for immunologic recovery. Guidelines should weigh immunologic benefits against long-term risks.

Keywords: HIV; child; immunologic; reconstitution; treatment failure.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-HIV Agents / administration & dosage*
  • Antiretroviral Therapy, Highly Active / standards*
  • CD4 Lymphocyte Count / methods
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • HIV Infections / immunology
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Infant
  • Infant, Newborn
  • Male

Substances

  • Anti-HIV Agents

Associated data

  • ISRCTN/ISRCTN73318385