Grant: Catalyst Grant: HIV/AIDS and Co-morbidities - Biomedical/Clinical

Plasmodium falciparum, the causative agent of the deadliest form of malaria, and HIV-1 are among the most important health problems worldwide being responsible for a combined 4 million deaths each year. Due to their extensive overlap in developing regions, especially Sub-Saharan Africa, co-infections with malaria and HIV-1 are a common occurrence but the interplay between the two diseases is far from being understood. Pregnant women have an increased risk of severe malaria infection especially during their first pregnancy and field studies have shown that HIV-1 peripheral and placental viral loads are increased in co-infected individuals suggesting that malaria could accelerate HIV-1 disease progression and facilitate viral transmission from the mother to the unborn child. However, the mechanisms responsible are poorly understood. In vitro exposure of immune cells to erythrocytes infected by P. falciparum can have a profound effect on their activation level. In turn, this has the potential to affect the way they interact with HIV-1 and might lead to an enhancement of HIV-1 infection. The placental barrier protecting the foetus from the mother's blood circulation is also known to be immunologically active and malaria parasites sequestering to the placenta have been proposed to lead to its activation. The focus of this work will thus be to study the interplay between an in vitro model of the placental barrier and malaria infected red blood cells and how this impacts HIV-1 infection. These studies will shed light on the impact of pregnancy-associated malaria on vertical transmission of HIV-1. Understanding the interplay between these two deadly diseases will facilitate the development of therapeutic measures tailored to a co-infection context allowing to reduce their impact on the lives of those affected.