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test the safety and efficacy of this new formulation in young children

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Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

The challenge

Increasing numbers of medicines are being developed, and access to new medicines in Africa is increasing. However, these positive trends are creating challenges for national regulatory agencies responsible for processing new drug registrations and monitoring the safety of drugs after they have been introduced.

With mass drug administration campaigns, large-scale immunisation programmes and increasing numbers of clinical trials, effective safety monitoring (pharmacovigilance) is increasingly essential.

Many national regulatory agencies lack the skilled workforce required to lead and manage pharmacovigilance systems. Furthermore, few have systematic processes in place for monitoring safety after drugs have been licensed for use. The PROFORMA project is therefore bringing multiple international partners together to strengthen pharmacovigilance systems in four East African countries – Ethiopia, Kenya, Rwanda and Tanzania.

The project is connecting pharmacovigilance experts from WHO Collaborating Centres in Pharmacovigilance, five medical universities, four national regulatory agencies and two Regional Centres of Regulatory Excellence in East Africa.

Using standardised WHO pharmacovigilance indicator tools, the project has mapped current pharmacovigilance systems in the four East African countries, identifying current strengths and gaps. These will be used to develop tailored interventions to build capacity in priority areas in each country. ‘Train the trainer’ models will be used to develop sustainable training programmes, taking advantage of expertise in local academic institutions.

The project aims to develop a cohort of pharmacovigilance-trained individuals across the multiple sectors involved in drug safety data collection and analysis. The project will train 12 postgraduate students (four PhD and eight master’s students) at European and African academic centres, in order to build regional pharmacovigilance expertise and local postgraduate programmes in pharmacovigilance. It will have a particular focus on clinical trials regulation and mass drug administration and immunisation programmes, and is working with national programmes to embed pharmacovigilance in ongoing campaigns.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The PROFORMA project is enhancing the capacity of the four countries to monitor the safety of new interventions being tested in clinical trials and after they have been introduced into routine use. As well as identifying potential adverse reactions for investigation, enhanced pharmacovigilance activities will help to maintain public confidence in large-scale health programmes such as vaccination and mass drug administration. By ensuring close integration with WHO and regional regulatory harmonisation initiatives, the project is also establishing a sustainable platform for developing national pharmacovigilance capacity.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact