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

PLoS Negl Trop Dis. 2024 Sep 30;18(9):e0012000. doi: 10.1371/journal.pntd.0012000. eCollection 2024 Sep.

Abstract

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.

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Coinfection* / epidemiology
  • Ethiopia / epidemiology
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • HIV Infections* / complications
  • HIV Infections* / epidemiology
  • HLA-A Antigens / genetics
  • Humans
  • Leishmaniasis, Visceral* / epidemiology
  • Male
  • Middle Aged
  • Young Adult

Substances

  • HLA-A Antigens

Grants and funding

This work was supported by the Research Foundation Flanders (FWO) [1S71721N fellowship to N.d.V.], a research grant of the University of Antwerp Research Fund (BOF) [FFB220027 to B.C. and N.d.V.], the Institute for Tropical Medicine Antwerp’s SOFI programme supported by the Department of Economy, Science and Innovation of the Flemish Government, and the Belgian Directorate General for Development Cooperation under the ITM-DGDC framework agreement FA-III & FAIV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.