Background Malaria during pregnancy is an important driver of maternal and neonatal health especially among HIV-infected women. In Africa, at least one million pregnant women are annually co-infected with Plasmodium and HIV. The interaction between the two infections is particularly deleterious during pregnancy, leading to an increased risk of malaria and HIV viral load. Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine is recommended for malaria prevention in HIV-uninfected women but it is contraindicated in those HIV-infected women on cotrimoxazole prophylaxis (CTXp).

Methods A randomized, double-blind, two-arm, placebo-controlled trial to evaluate the safety and efficacy of dihydroartemisinin-piperaquine (DHA-PPQ) for IPTp was conducted in HIV-infected pregnant women receiving CTXp, antiretroviral drugs and long lasting insecticide treated nets in five sites from Gabon and Mozambique. Women attending the first antenatal care clinic visit, resident in the study area and with a gestational age ≤28 weeks were randomized to receive either monthly IPTp with DHA-PPQ or placebo. The three day IPTp administration was always done under direct observation. Women were followed up until one month after the end of pregnancy.

Results A total of 666 HIV-infected pregnant women were enrolled in the trial between September 2019 and November 2021. The prevalence of maternal peripheral parasitemia at delivery (primary study endpoint) was unexpectedly low during the study period and no significant differences were found between groups. However, the composite of Plasmodium infection (detected by any diagnostic test during pregnancy or delivery) was significantly decreased in the DHA-PPQ group (RR=0.48, 95CI 0.27–0.84; p=0.010). There were no differences in the prevalence of adverse pregnancy outcomes and serious adverse events across groups.

Conclusion In a context of low malaria transmission, adding monthly IPTp- DHA-PPQ to CTXp in HIV-pregnant women is safe and it is associated with a decreased risk of clinical malaria and overall Plasmodium infection in pregnancy.