Children with HIV in Africa – Pharmacokinetics and adherence/acceptability of simple antiretroviral regimens
African paediatric HIV trial
What was this study about?
CHAPAS-3 evaluated new antiretroviral fixed dose combination (FDC) and single drugs in HIV infected African children. The primary end point of the trial was a comparison of toxicities and side effects between the treatment arms. The study also investigated how effectively the different drug combinations worked against HIV, and looked at a number of additional outcomes including pharmacokinetics (what happens to the drugs in the children’s bodies) and cost-effectiveness of the different antiretroviral regimens. CHAPAS-3 also measured adherence (how well the children were able to take treatment over the longer term) and investigated how acceptable these drugs were to the children (e.g. whether they were easy to take).
Children were randomly allocated to one of the three treatment groups, where they would received either stavudine, abacavir or zidovidine in combination with two other antiretroviral drugs. The hypothesis being tested was that the new FDC tablets containing abacavir or zidovudine would cause less toxicity and improve the adherence and acceptability compared to stavudine-based regimens. The FDC tablets were manufactured in ratios recommended for children by the WHO Formulation Working Group and administered according to WHO weight-band dosing tables.
There was also a component of the study that looked at cardiac and vascular function, by measuring pulse wave velocity, carotid intimal thickness and immune markers of inflammation. These data were compared to a group of HIV-negative children who were recruited into the CHAPAS-3 study as a control group. Another component of the study investigated lipodystrophy; the abnormal distribution of body fat that can be associated with HIV and HIV medication. This is much more difficult to study in children, because their body shapes are very different to adults – and even more so in settings like Uganda and Zambia where malnutrition is common.
What difference did this study make?
This study has been incorporated into WHO 2015 guidelines to recommend abacavir first-line for HIV-infected children.
Type of study
Who funded the study?
The trial was funded by the European Developing Countries Clinical Trials Partnership (EDCTP), Medical Research Council UK (MRC UK), Department for International Development (DfID UK), the Ministerio de Sanidad y Consumo Spain and the Health Research Board Ireland. Drugs were supplied by Cipla Ltd, India.
When did it take place?
The first child was randomised on 8th November 2010 and the last child on 28th December 2011. The overall duration of the trial was three and a half years, with all children being followed-up for a minimum of 96 weeks. The children started to exit the trial at the end of October 2013, with the final children being transferred into the National Programmes in January 2014.
Where did it take place?
University Teaching Hospital, Lusaka, Zambia; Baylor Centre of Excellence at Mulago Hospital, Kampala, Uganda; Joint Clinical Research Centre, Kampala, Uganda and a JCRC satellite clinic in Gulu, Northern Uganda.
Who was included?
CHAPAS-3 enrolled 480 children between the ages of 1 month and 13 years from Uganda and Zambia. The children were either treatment naïve (had never received antiretroviral drugs before, except at birth to prevent mother to child transmission) or, if they had already been taking antiretrovirals including stavudine, had an undetectable viral load.