Project: Improving maternal and infant health by reducing Malaria risks in African women: evaluation of the safety and efficacy of dihydroartemisinin-piperaquine for intermittent preventive treatment of Malaria in HIV-infected pregnant women

Acronym	Mamah (Reference Number: RIA2016MC-1613)
Duration	01/03/2018 - 28/02/2023
Project Topic	Malaria infection during pregnancy is an important driver of maternal and neonatal health especially among HIV-infected women. In Africa, at least one million pregnancies are co-infected with malaria and HIV annually. The interaction between the two infections is particularly deleterious in pregnancy, leading to increased risk of malaria and HIV viral load, which may increase the frequency of mother to child transmission of HIV (MTCT-HIV). Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-uninfected women but it is contraindicated in those HIV-infected on cotrimoxazole prophylaxis (CTXp) due to potential adverse effects. A recent EDCTP-funded trial showed that an effective antimalarial added to CTXp and long-lasting insecticide treated nets (LLITNs) in HIV-infected pregnant women improves malaria prevention and maternal health. However, the antimalarial used (mefloquine) was not well tolerated and it was associated with an elevation on HIV viral load at delivery and a two-fold increased risk of MTCT-HIV. These findings highlight the need to find alternative drugs with better tolerability and safety profile to prevent malaria in this vulnerable group and to further study the pharmacological interactions between antimalarial and antiretroviral (ARV) drugs. Dihydroartemisinin-piperaquine (DHA-PPQ), because of its long half-life and good tolerability has been shown to improve antimalarial protection in HIV-uninfected women, constituting the most promising candidate for IPTp in HIV-infected pregnant women. However, there is limited information on the pharmacokinetics of DHA-PPQ with concomitant use of ARV drugs and CTX, particularly in pregnancy. A randomized double blind placebo-controlled trial to evaluate the safety and efficacy of DHA-PPQ for IPTp in HIV-infected pregnant women receiving CTXp and ARV drugs and using LLITNs will be conducted in two sub-Saharan countries where malaria and HIV infection are moderate to highly prevalent. In addition, the possibility for a pharmacokinetic interaction between DHA-PPQ and ARV drugs will be assessed in a sub-sample of participants. Women will receive ARV therapy according to national guidelines and their infants will be followed until one year of age to evaluate the impact of DHA-PPQ on MTCT-HIV. The findings of this project will provide conclusive evidence to reduce the burden of two of the most important poverty-related diseases (PRDs), in one of the most vulnerable groups, HIV-infected pregnant women exposed to malaria. Thus, the proposed project falls largely within EDCTP’s scope of improving prevention of PRDs and maternal and child health, while contributing to networking of European and African institutions.
Network	EDCTP2
Call	Clinical trials and operational research studies to optimise the use of products for poverty-related diseases in mothers, newborns, children and/or adolescents

Project partner

Number	Name	Role	Country
1	Fundación Privada Instituto de Salud Global Barcelona	Coordinator	Spain
2	Bernhard-Nocht-Institut für Tropenmedizin	Partner	Germany
3	Centre de Recherches Médicales de Lambaréné	Partner	Gabon
4	Eberhard Karls Universität Tübingen	Partner	Germany
5	Fundaçao Manhiça	Partner	Mozambique
7	Medizinische Universitaet Wien	Partner	Austria