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

Using CD4 percentage and age to optimize pediatric antiretroviral therapy initiation

Dwight E Yin  1 , Meredith G Warshaw  2 , William C Miller  3 , Hannah Castro  4 , Susan A Fiscus  5 , Lynda M Harper  4 , Linda J Harrison  2 , Nigel J Klein  6 , Joanna Lewis  7 , Ann J Melvin  8 , Gareth Tudor-Williams  9 , Ross E McKinney Jr  10 ; PENPACT-1 (PENTA 9/PACTG 390) Study Team
Collaborators, Affiliations
Clinical Trial

Using CD4 percentage and age to optimize pediatric antiretroviral therapy initiation

Dwight E Yin et al. Pediatrics. 2014 Oct.

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.

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Figures

FIGURE 1
FIGURE 1
Cumulative proportion of children with CD4% recovery to normal versus weeks after HAART initiation, by baseline WHO Immunodeficiency Classification (“mild,” “advanced,” “severe”). Primary outcome is CD4% ≥10th percentile for age by week 192, marked by vertical dashed line. P value is from log-rank statistic.
FIGURE 2
FIGURE 2
Cumulative proportion of children with CD4% recovery to normal versus weeks after HAART initiation, by age at HAART initiation (0–4, 5–9, 10–17 years). Primary outcome is CD4% ≥10th percentile for age by week 192, marked by vertical dashed line. P value is from log-rank statistic.
FIGURE 3
FIGURE 3
Relationship between age at HAART initiation and (A) proportion of children with normal CD4% within 4 years, (B) CD4% at 4 years, (C) proportion of children with normal CD4% at 4 years, (D) proportion of children with viral failure within 4 years. Panels A, B, and C illustrate splines; panel D illustrates a cubic function.
See this image and copyright information in PMC

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