CHAPAS-3 trial confirms high efficacy of WHO-preferred abacavir plus lamivudine ART in children

12 October 2015

The EDCTP-funded CHAPAS-3 trial is the first randomised controlled trial in African children to compare three ‘backbones’ for antiretroviral treatment (ART) regimens. All regimens were shown to have low toxicity and good clinical, immunological, and virological responses. This trial provides strong evidence to support the WHO guidelines for first-line paediatric ART. The trial allays concerns of reduced efficacy raised by observational studies. The results, published in The Lancet Infectious Diseases on 6 October 2015, support clinicians and policy makers in implementing the current WHO guidelines for ART in children.

Publication in The Lancet: Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial

The study, coordinated by Dr Veronica Mulenga (University Teaching Hospital, Zambia), was the first randomised controlled trial conducting a head-to-head comparison of the three most relevant nucleoside reverse transcriptase inhibitors (NRTIs) for paediatric treatment.

“We identified no major differences between the NRTIs… but did find higher drug susceptibility to relevant second-line NRTIs if abacavir was used first-line, thus providing evidence to support the WHO 2013 recommendation for its use as the preferred first-line NRTI for children. Use of abacavir also enables a once-daily ART regimen to be constructed for children…”

Mulenga, Veronica et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. (2015) The Lancet Infectious Diseases, p. 2

CHAPAS-3 trial

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.

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