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Younger age, higher CD4 count at ART initiation increased recovery odds
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Recent data show children who received antiretroviral therapy at a higher CD4 percentage and younger age were more likely to experience immunologic recovery than their older peers with lower CD4 percentage.
The Pediatric AIDS Clinical Trials Group 390/Pediatric European Network for Treatment of AIDS (PENPACT-1) was an international, multicenter phase 2/3, randomized, open-label trial conducted between September 2002 and 2005. Researchers randomly assigned children with vertically acquired HIV-1 to start ART with two nucleoside reverse transcriptase inhibitors plus either a protease inhibitor or non-nucleoside reverse transcriptase inhibitor and to switch from first-line to second-line ART when viral loads were 1,000 copies/mL or 30,000 copies/mL. Study participants (n=263) were aged 1 month to 18 years and had not received ART or were only treated to reduce mother-to-child transmission. CD4 percentage and HIV RNA viral loads were measured at baseline (week 0) and every 2 weeks for the next 2 months, then every 12 weeks until 4 years of follow-up were completed in August 2009.
The estimated probability of achieving a normal CD4 percentage within 4 years was 72% among children with immunosuppression at baseline. Among these 162 children, mean CD4 percentage at 4 years was 30.9. Fifty-six percent of children had a normal CD4 percentage at 4 years.
Children with any immune status at baseline (n=209) had a mean CD4 percentage of 32.8 at 4 years. Sixty-four percent of these children had a normal CD4 percentage at 4 years.
Analysis indicated that as baseline CD4 percentage increased, the percentage of children who ever achieved a normal CD4 percentage within 4 years and those with a normal percentage at 4 years increased.
CD4 percentage recovery within 4 years was significantly associated with age. When adjusting for gender and race, each 5-year increase in age at ART initiation decreased the number of children with a normal CD4 percentage by an estimated 19%. As age at ART initiation increased by 5-year increments, CD4 percentage at 4 years decreased by 2.9 percentage points and the proportion of children with a normal CD4 percentage at 4 years decreased by 7%.
Baseline CD4 percentage and age were significantly associated with the probability of ever recovering a normal CD4 percentage within 4 years. As age increased, baseline CD4 percentage influenced the ability to recover a normal CD4 percentage within 4 years. However, the association between baseline CD4 percentage and age were not significant for CD4 percentage at 4 years or the number of children with normal CD4 percentage at 4 years.
Adolescents with WHO-defined “severe” immunosuppression were the least likely to recover their CD4 percentage, but a small sample size of adolescents may limit this finding, according to researchers.
“Earlier highly active ART initiation in children with vertically acquired HIV-1 substantially improves immunologic recovery within 4 years. Optimizing treatment timing by CD4 percentage and age may have significant long-term immunologic benefits. Older children and adolescents, in particular, may benefit from earlier treatment,” the researchers concluded.
Disclosure: One researcher serves on the advisory board of Janssen Pharmaceuticals. The other researchers report no relevant financial disclosures.
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