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
HLA allelic variation affects susceptibility to and protection against TB infection.
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Data describing HLA associations with TB in HIV-positive individuals is limited.
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Some HLA alleles are associated with protection against TB co-infection in HIV.
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Knowledge of protective HLA alleles may assist with future vaccine development.
Abstract
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*29:11 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 -DRB1*11:01 were protective, even for CD4+ T-cell count <350 cells/mm3. For initial TST-positivity and subsequent TB disease, HLA-A*01:01 and -DRB1*11:01 conveyed protection including for those with CD4+ T-cell count <350 cells/mm3.
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.
