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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

Globally, 85 million women every year become pregnant in areas of Plasmodium falciparum malaria transmission. Without interventions, malaria infections have the potential to cause 900,000 low-birth-weight deliveries, leading to the deaths of 200,000 newborn babies and 10,000 mothers.

To prevent these adverse outcomes, WHO recommends a range of measures, including preventive treatment with antimalarial drugs and use of insecticide-impregnated bednets. However, across sub-Saharan Africa malarial parasites are increasingly developing resistance to the main drug combination used to prevent infections, sulphadoxine–pyrimethamine (SP).

For countries in sub-Saharan Africa, it can be challenging to identify the most appropriate approach to prevent and manage malaria. Whether to use diagnostic screening and choice of drug depends on a range of factors, particularly the intensity of malaria transmission and local levels of resistance to SP. 

During the past decade, the Malaria in Pregnancy (MiP) Consortium has carried out a range of important studies in sub-Saharan Africa examining the effectiveness of SP and alternative forms of chemoprevention for use alongside bednets, as well as the potential utility of screening for malaria during pregnancy.

The Consortium’s work fed into WHO policymaking on malaria prevention in pregnancy, which recommended tailored strategies for areas according to their levels of SP resistance and malaria transmission intensity. In the IMPP-ACT project, the MiP Consortium is building on its previous work to support evidence-based policymaking and implementation to minimise the impact of malaria in pregnancy.

The team has developed tools to enable health policymakers to identify and deploy the safest and most cost-effective strategies based on local patterns of disease and SP resistance. It has also undertaken work exploring national decision-making processes in four focus countries (The Gambia, Mali, Kenya and Malawi), and provided technical expertise to countries to support changes in policy and implementation of new policies. Regional meetings have been held in East Africa and West Africa to communicate its findings, with technical support offered to national policymakers and technical agencies involved in policy development and implementation.

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 project ensured that national policymaking and programmatic activities in multiple malaria-endemic countries have been informed by the latest findings on malaria prevention in pregnancy, helping to protect the health of both pregnant women and their unborn children. It also generated important insight into the processes involved in the translation of research evidence into national policies and implementation plans.

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