The CHAPAS-3 (Children with HIV 1 in Africa, Pharmacokinetics and Adherence/Acceptability of Simple Antiretroviral Regimens) was an open-label randomised phase II/III trial conducted in Zambia and Uganda to evaluate new solid, dispersible scored antiretroviral fixed-dose combination and single drugs in African children.
A total of 478 children (age 1 month to 13 years) were randomised to study arms which received fixed-dose combination tablets of one of the three NRTIs (abacavir, stavudine, or zidovudine) plus lamivudine in combination with nevirapine or efavirenz. All combinations were dosed according to WHO weight bands. The trial included 365 ART-naive children and 113 virologically suppressed ART-experienced children on a stavudine-containing first-line regimen for 2 years or more. The trial compared the pharmacokinetics, toxicity, acceptability, adherence, efficacy and cost-effectiveness of these first-line antiretroviral regimens. The study drugs were donated by CIPLA Pharmaceuticals, India.
Clinical outcomes for all three NRTIs presented low (4%) mortality, high (≥80%) viral load suppression rates in ART-naive children, high (>96%) maintenance of viral suppression at 48 weeks in ART-experienced children, and no evidence of differential CD4% recovery across randomised groups. All three NRTI backbones with efavirenz or nevirapine were shown to have low toxicity and to produce high viral load suppression rates independent of the NRTI used. Abacavir has very low toxicity in African children, a superior resistance profile for second-line NRTI sequencing, and is the only once-daily licensed NRTI fixed-dose combination (with lamivudine) for children, supporting its preferred use in first-line ART.