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

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. Author summary: Human immunodeficiency virus (HIV) co-infection is a major challenge for the control of visceral leishmaniasis (VL), particularly in Ethiopia where both frequently occur. VL-HIV disease is often hard to treat, and some treated patients will relapse after initially thought to be cured. However, there is a long period of asymptomatic Leishmania infection prior to the development of VL-HIV symptoms, and tackling the infection at this stage will be valuable in the effort to combat VL-HIV disease. However, this requires good understanding of human risk factors for VL development. In this work, we tested the Human Leukocyte Antigen gene region and the association with VL disease development, as genetic risk factors. We identified a preliminary association between the HLA-A*03:01 gene variant and an increased risk for VL development. This would need to be tested again in a larger study, to assess whether it can be used to see if asymptomatic Leishmania-infected individuals will develop VL disease. [ABSTRACT FROM AUTHOR]