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.

中文翻译：

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尽管有家庭暴露和免疫抑制，人类白细胞抗原与人类免疫缺陷病毒 1 感染者预防结核病感染和疾病的关联

背景 确定人类白细胞抗原 (HLA) 等位基因与 HIV 感染成人中结核菌素皮肤试验 (TST) 阳性和活动性结核病的风险和预防相关性的关联。方法 从 754 名感染 HIV 的成年人全血中提取基因组 DNA。HLA-A、-B、-C 和-DRB1 位点通过下一代测序方法进行基因分型。通过是否存在 TST 免疫转换和活动性结核病来分析 HLA 等位基因，并通过接触家庭结核病接触者、CD4+ T 细胞计数和活动性结核病、TST 阳性进一步分层。结果 HLA-A*29:11 和 -B*45:01/07 与 TST 阳性相关，而 HLA-A*24:02、-A*29:02 和 -B*15:16 与 TST 阴性相关. 在有家庭结核病接触者的参与者中，HLA-A*66:01、-A*68:02 和 -B*49:01 与 TST 阴性相关。对于结核病，HLA-B*41:01、-C*06:02、-DRB1*04:01 和-DRB1*15:01 与易感性相关，而 HLA-B*07:02 和-DRB1*11 :01 具有保护作用，即使 CD4+ T 细胞计数 <350 个细胞/mm3。对于初始 TST 阳性和随后的结核病，HLA-A*01:01 和 -DRB1*11:01 提供保护，包括对 CD4+ T 细胞计数 <350 个细胞/mm3 的患者。结论 几个 HLA 等位基因被认为与 HIV 感染者的 TB 感染、风险和自然保护相关。HLA 关联可能有助于对 HIV 感染者进行风险分层。保护性等位基因可能有助于未来结核病疫苗的开发。对于初始 TST 阳性和随后的结核病，HLA-A*01:01 和 -DRB1*11:01 提供保护，包括对 CD4+ T 细胞计数 <350 个细胞/mm3 的患者。结论 几个 HLA 等位基因被认为与 HIV 感染者的 TB 感染、风险和自然保护相关。HLA 关联可能有助于对 HIV 感染者进行风险分层。保护性等位基因可能有助于未来结核病疫苗的开发。对于初始 TST 阳性和随后的结核病，HLA-A*01:01 和 -DRB1*11:01 提供保护，包括对 CD4+ T 细胞计数 <350 个细胞/mm3 的患者。结论 几个 HLA 等位基因被认为与 HIV 感染者的 TB 感染、风险和自然保护相关。HLA 关联可能有助于对 HIV 感染者进行风险分层。保护性等位基因可能有助于未来结核病疫苗的开发。