HLA-A*03:01 is 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 a strong 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. ### Competing Interest Statement W.A. received a travel grant by Omixon to participate in the European Federation for Immunogenetics conference to present the preliminary results of this work. Omixon had no role in study design, data collection and analysis, preparation of the manuscript, nor the decision to publish. ### Funding Statement This work was supported by the Research Foundation Flanders (FWO) with fellowship grant number 1S71721N to N.d.V., a research grant of the University of Antwerp Research Fund (BOF) with grant number FFB220027 to B.C. and N.d.V, and the Institute of Tropical Medicine Antwerp 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 & FA-IV. The funders had no role in study design, data collection and analysis, decision to publish, or the preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Ethiopian National Research Ethics Review Committee, the University of Gondar Institutional Review Board, and the Institute of Tropical Medicine Antwerp Institutional Review Board. All patients consented to long-term biobanking and future research on their biobanked samples. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data cannot be shared publicly because of institutional restriction to publishing information that could be used to de-identify individuals in the study. Data are available from the ITM institutional data access committee for researchers who meet the criteria for access to confidential data. This committee can be contacted at the following email address: ITMresearchdataaccess@itg.be Code is available on https://github.com/BioinformaNicks/PreLeisHLA