Using CD4 Percentage and Age to Optimize Pediatric Antiretroviral Therapy Initiation

Abstract

WHAT'S KNOWN ON THIS SUBJECT:In HIV-infected children, decisions to start antiretroviral therapy must weigh immunologic benefits against potential risks. Current guidelines recommend using CD4 percentage and age when deciding to start treatment. Population-level effects of these factors on immunologic recovery are unknown. WHAT THIS STUDY ADDS:Starting antiretroviral therapy at higher CD4 percentages and younger ages maximizes potential for immunologic recovery. However, not all benefits are sustained, and viral failure may occur. Our results help clinicians better weigh immunologic benefits against viral failure risks. 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.

Baseline CD4 T Cell Level Predicts Recovery Rate after Initiation of ART in HIV Infected Nigerians

“…Doubling of preceding CD4 T cell levels by significant proportion of the population at each point of analysis also corroborates the conclusion. Furthermore, it confirms previous reports [8,[11][12][13][14][15][16][17] of increase in CD4 T-lymphocyte cell counts with the use of effective ART.…”

Virological and Immunological Long-Term Outcome of Human Immunodeficiency Virus-1 Infected Children Treated before One Year and after Two Years of Age in a Resource-Limited Setting of South Africa

“…Results were unconclusive. Four studies [25][26][27][28] concluded the absence of influence of age at baseline and five studies [14,23,[29][30][31] [16]. In our study, mean CD4 + % was normal in both cohorts.…”

“…The European-American PENPACT-1 study [31], analyzed combined effects of CD4 + % and age at baseline. They found a significant interaction between CD4 + % and age on the probability of ever recovering a normal CD4 + % within 4 years.…”

Advances in Pediatric Pharmacology, Therapeutics, and Toxicology

“…Investigators of the Pediatric AIDS Clinical Trials 390/Paediatric European Network for Treatment of AIDS 9 (PENPACT-1) quantified the impacts of ART initiation at different ages and CD4% on CD4% recovery after 4 years in pediatric patients 0–17 years of age [58]. Overall, 72% of 162 vertically infected, immunosuppressed children recovered to normal CD4% within 4 years of ART initiation.…”

“…Additionally, for each 5-year increase in baseline age, the proportion of children achieving recovery declined by 19%. The study concluded that combining baseline CD4% and age effects resulted in >90% recovery after 4 years when ART was initiated with mild immunosuppression at any age or with advanced immunosuppression <3 years of age [58]. …”