Enhanced severity of malaria infection in simian immunodeficiency virus (SIV) infected rhesus macaques (129.15)

Abstract

Abstract Epidemic HIV and malaria co-occur in Africa and Asia. We developed a rhesus macaque model of SIV and Plasmodium fragile infection to model human co-infection. From available human data, we hypothesized that P. fragile infection during acute SIV infection enhances immune activation and thereby virus replication and, conversely, that SIV infection enhances parasitemia and parasite transmission in co-infected macaques. Immunological, parasitological and virological parameters were assessed throughout the course of infection by multiparameter flow cytometry, blood smears, and PCR. P. fragile-only infection resulted in increased CCR5 and Ki67 expressing CD4+ T cells, potential target cells of SIV, during peak parasitemia. Indeed, acute malaria infection was associated with increased viremia in co-infected animals. Further, SIV-induced immunosuppression was correlated with severe anemia and uncontrolled parasitemia in co-infected animals. Importantly, oocyst numbers in mosquitoes that fed on blood from co-infected animals were higher than those that fed on blood from P. fragile only infected animals. These data suggest that co-infection increases the rate of transmission of both SIV and malaria in co-infected animals. Our model can be used to elucidate the mechanisms that underlie increased transmission and altered immunity during HIV-P. falciparum co-infection in humans and to test new therapies. NIH IR21AI077373, T32 AMID, STAR, VSTP