Publications

Funding for clinical research |drugs, vaccines, microbicides, diagnostics | HIV/AIDS, tuberculosis, malaria, other infectious diseases |sub-Saharan Africa

EDCTP portfolio: Malaria

The MAMAH study is evaluating a new drug combination for preventing malaria infections in pregnant women with HIV.

Preventing malaria in pregnant women with HIV

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. 

The challenge

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 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.

Impact


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.

EDCTP portfolio: HIV & HIV-associated infections

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

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M