Human Leukocyte Antigen Associations With Protection Against Tuberculosis Infection And Disease In Human Immunodeficiency Virus-1 Infected Individuals, Despite Household Tuberculosis Exposure And Immune Suppression

Background: To determine the association of human leukocyte antigen (HLA) alleles as correlates of risk for and protection against tuberculin skin test (TST) positivity and active TB disease amongst HIV-infected adults.Methods: Genomic DNA was extracted from 754 HIV-infected adults whole-blood. HLA-A, -B, -C and -DRB1 loci were genotyped by next generation sequencing methods. HLA alleles were analysed by the presence/absence of TST immune conversion and active TB disease and further stratified by exposure to a household TB contact, CD4(+) T-cell count and, for active TB disease, TST-positivity.Results: HLA-A*29: I I and - B *45:01/07 were associated with TST positivity, while HLA-A *24:02, -A*29:02 and -B *15:16 with TST-negativity. In participants with a household TB contact, HLA-A *66:01, A*68:02 and -B *49:01 were associated with TST-negativity. For TB disease, HLA-B *41:01, -C*06:02, -DRB1 *04:01 and -DRB1 *15:01 were associated with susceptibility, while HLA-B *07:02 and -DRBI *11:01 were protective, even for CD4 + T-cell count <350 cells/mm(3). For initial TST-positivity and subsequent TB disease, HLAA*01:01 and -DRBI * 11:01 conveyed protection including for those with CD4(+) T-cell count <350 cells/mm(3).Conclusion: Several HLA alleles are noted as correlates of TB infection, risk and natural protection in HIV-infected individuals. HLA associations may enable risk stratification of those with HIV infection. Protective alleles may assist in future TB vaccine development.