“
crucial in

widening African

children’s access

to antiretrovirals

”

Bringing antiretroviral drugs to children

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

The challenge

In Africa, at least a million pregnant women are affected by both HIV and malaria infections. The two infections have mutually reinforcing effects, leading to higher parasite loads and greater viral replication. This is harmful to mothers, but also to the developing fetus, including an increased risk of mother-to-child transmission of HIV.

Because of the risks of malaria in pregnancy, WHO recommends that pregnant women receive preventive treatment with antimalarial drugs, generally sulphadoxine–pyrimethamine (SP). However, this is not recommended for women with HIV, because of the risk of side effects when women are also taking cotrimoxazole, an antibiotic used to prevent HIV-related infections. 

A previous EDCTP-funded study found that an alternative to SP, mefloquine, used alongside insecticide-treated bednets and cotrimoxazole, offered good protection against malaria. However, it caused unpleasant symptoms in women, and was also associated with elevated viral replication and an increased risk of mother-to-child transmission of HIV.

The MAMAH study is assessing whether a different antimalarial drug, dihydroartemisinin–piperaquine (DP), may be a more suitable alternative. It has proven safe and effective in pregnant women without HIV infections, but there are limited data on its use in HIV-infected pregnant women.

Working in two African countries, the MAMAH team is running a placebo-controlled trial of DP for malaria prevention in HIV-infected pregnant women who are receiving antiretroviral therapy and cotrimoxazole. As well as impacts on malaria in mothers, the project will explore whether DP affects the pharmacokinetics of antiretroviral drugs and cotrimoxazole, and infants will be followed up to the age of one year to assess any impacts on mother-to-child transmission of HIV.

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 MAMAH study will provide data on a possible approach to malaria prevention in a highly disadvantaged group – pregnant women with HIV. Effective malaria prevention in this group would benefit the health not only of mothers but also their offspring – improving maternal health, reducing infant mortality, and increasing birthweight, with long-term benefits for child health and development.

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