A preliminary indication that HLA-A*03:01 may be associated with visceral leishmaniasis development in people living with HIV in Ethiopia

by Nicky de Vrij, Romi Vandoren, Kadrie Ramadan, Anke Van Hul, Ann Ceulemans, Mekibib Kassa, Roma Melkamu, Arega Yeshanew, Tadfe Bogale, Hailemariam Beyene, Kasaye Sisay, Aderajew Kibret, Dagnew Mersha, Wim L. Cuypers, Florian Vogt, Saskia van Henten, Koert Ritmeijer, Thao-Thy Pham, Pieter Meysman, Kris Laukens, Bart Cuypers, Ermias Diro, Rezika Mohammed, Johan van Griensven, Wim Adriaensen

Human immunodeficiency virus (HIV) co-infection is a major challenge for visceral leishmaniasis (VL) control, particularly in Ethiopia where the incidence of both pathogens is high. VL-HIV often leads to high rates of antileishmanial treatment failure and recurrent VL disease relapses. Considering the high prevalence of HIV and Leishmania in the Ethiopian population, preventing the progression of asymptomatic Leishmania infection to disease would be a valuable asset to VL disease control and to the clinical management of people living with HIV (PLWH). However, such a strategy requires good understanding of risk factors for VL development. In immunocompetent individuals living in Brazil, India, or Iran, the Human Leukocyte Antigen (HLA) gene region has been associated with VL development. We used NanoTYPE, an Oxford Nanopore Technologies sequencing-based HLA genotyping method, to detect associations between HLA genotype and VL development by comparing 78 PLWH with VL history and 46 PLWH that controlled a Leishmania infection, all living in a VL endemic region of North-West Ethiopia. We identified an association between HLA-A*03:01 and increased risk of VL development (OR = 3.89). These data provide candidate HLA alleles that can be further explored for inclusion in a potential Leishmania screen-and-treat strategy in VL endemic regions.