Malaria and HIV: a double threat for pregnant women in Sub-Saharan Africa

Women in Sub-Saharan Africa (SSA) face significant risks when they become pregnant. In addition to the risk of obstetric complications confronted by all women during pregnancy, women in SSA are particularly vulnerable to malaria and HIV infection. Due to the geographical overlap of malaria and HIV epidemics, a significant number of co-infections occur. Infection with either malaria or HIV can lead to serious illness and death for mothers and their infants. Furthermore, infection with one can exacerbate infection with the other, making treatment challenging.

In SSA, approximately one million pregnancies each year are complicated by co-infection with malaria and HIV [1]. HIV lessens pregnancy-specific malaria immunity meaning pregnant women infected with HIV are more likely to have symptomatic malaria, severe anaemia and placental malaria. Placental malaria and HIV co-infection have been associated with adverse pregnancy outcomes, such as low birth weight and preterm delivery, higher rates of neonatal mortality, and, in some settings, increased risk of mother-to-child transmission of HIV. In turn, infection with malaria in HIV-infected pregnant women has been shown to increase HIV viral replication and speed disease progression [1].

Concurrent management of malaria and HIV in pregnancy is not straightforward. There are increasing concerns over drug interactions between antimalarials and antiretrovirals and their potential impact on drug efficacy and/or toxicity [2, 3]. Prevention of malaria and HIV co-infection is therefore critical to reducing the burden of adverse maternal and neonatal outcomes related to co-infection.

Despite being the most vulnerable population, HIV-infected pregnant women and their infants are the least protected against malaria. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), a highly effective and recommended approach for preventing pregnancy-related malaria and its complications in pregnant women, is not recommended for HIV-infected women receiving antiretroviral therapy (ART) and prophylactic treatment for opportunistic infections, due to potential adverse drug reactions [4]. Thus, alternative antimalarials drugs need to be evaluated for use in HIV-infected pregnant women. Suitable drugs for IPTp must be safe for both the mother and the foetus, able to be given during regular antenatal care visits and provide long-lasting protection.

The Malaria in Pregnancy Preventive Alternative Drugs (MiPPAD) study included two large randomized controlled trials to test mefloquine (MQ) as an alternative drug for malaria prevention in HIV-negative and HIV-positive pregnant women from five sub-Saharan countries. Both trials found that MQ can reduce malaria infections and improve overall health in pregnant women. However, while MQ did not have any impact on the mortality and morbidity of infants born to mothers who were HIV-negative when compared with women taking SP, it was associated with an increased risk of mother to child transmission of HIV when compared with placebo [5-7]. We hypothesized that this association could be a result of an interaction between MQ and antiretrovirals, although further studies are needed to fully understand these results.

More evidence is needed to inform clinical decisions and recommendations for prophylaxis and treatment of malaria and HIV co-infection in pregnancy. Further research on alternative drugs for IPTp in HIV-infected pregnant women, together with a more comprehensive understanding of potential drug interactions between antiretrovirals and antimalarials in pregnancy, is key for guiding the design of safe and effective interventions to improve the health of mothers and their infants in SSA.

References

1. Gonzalez, R., et al., HIV and malaria interactions: where do we stand? Expert Rev Anti Infect Ther, 2012. 10(2): p. 153-65.
2. Rattanapunya, S., et al., Pharmacokinetic interactions between artesunate-mefloquine and ritonavir-boosted lopinavir in healthy Thai adults. Malar J, 2015. 14: p. 400.
3. Rattanapunya, S., et al., Pharmacokinetic Interactions Between Quinine and Lopinavir/Ritonavir in Healthy Thai Adults. Am J Trop Med Hyg, 2015. 93(6): p. 1383-90.
4. WHO, Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection 2016. Reccomendations for a public health approach. Second edition. 2016, World Health Organization.
5. Gonzalez, R., et al., Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-infected women receiving cotrimoxazole prophylaxis: a multicenter randomized placebo-controlled trial. PLoS Med, 2014. 11(9): p. e1001735.
6. Gonzalez, R., et al., Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-negative women: a multicentre randomized controlled trial. PLoS Med, 2014. 11(9): p. e1001733.
7. Ruperez, M., et al., Mortality, Morbidity, and Developmental Outcomes in Infants Born to Women Who Received Either Mefloquine or Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment of Malaria in Pregnancy: A Cohort Study. PLoS Med, 2016. 13(2): p. e1001964.