Centre of Excellence for Health, Immunity and Infections (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia.
AIDS. 2021 Apr 1;35(5):783-789. doi: 10.1097/QAD.0000000000002800.
The Strategic Timing of AntiRetroviral Treatment (START) and Strategies for Management of Antiretroviral Therapy (SMART) trials demonstrated that ART can partly reverse clinically defined immune dysfunction induced by HIV replication. As control of HIV replication is influenced by the HLA region, we explored whether HLA alleles independently influence the risk of clinical events in HIV+ individuals.
Cohort study.
In START and SMART participants, associations between imputed HLA alleles and AIDS, infection-related cancer, herpes virus-related AIDS events, chronic inflammation-related conditions, and bacterial pneumonia were assessed. Cox regression was used to estimate hazard ratios for the risk of events among allele carriers versus noncarriers. Models were adjusted for sex, age, geography, race, time-updated CD4+ T-cell counts and HIV viral load and stratified by treatment group within trials. HLA class I and II alleles were analyzed separately. The Benjamini--Hochberg procedure was used to limit the false discovery rate to less than 5% (i.e. q value <0.05).
Among 4829 participants, there were 132 AIDS events, 136 chronic inflammation-related conditions, 167 bacterial pneumonias, 45 infection-related cancers, and 49 herpes virus-related AIDS events. Several associations with q value less than 0.05 were found: HLA-DQB1∗06:04 and HLA-DRB1∗13:02 with AIDS (adjusted HR [95% CI] 2.63 [1.5-4.6] and 2.25 [1.4-3.7], respectively), HLA-B∗15:17 and HLA-DPB1∗15:01 with bacterial pneumonia (4.93 [2.3-10.7] and 4.33 [2.0-9.3], respectively), and HLA-A∗69:01 with infection-related cancer (15.26 [3.5-66.7]). The carriage frequencies of these alleles were 10% or less.
This hypothesis-generating study suggests that certain HLA alleles may influence the risk of immune dysfunction-related events irrespective of viral load and CD4+ T-cell count.
抗逆转录病毒治疗的战略时机（START）和抗逆转录病毒治疗管理策略（SMART）试验表明，ART 可以部分逆转 HIV 复制引起的临床定义的免疫功能障碍。由于 HIV 复制的控制受 HLA 区域的影响，我们探讨了 HLA 等位基因是否独立影响 HIV 感染者发生临床事件的风险。
队列研究。
在 START 和 SMART 参与者中，评估了推断的 HLA 等位基因与艾滋病、感染相关癌症、疱疹病毒相关艾滋病事件、慢性炎症相关疾病和细菌性肺炎之间的关联。使用 Cox 回归估计等位基因携带者与非携带者发生事件的风险比。模型根据性别、年龄、地理位置、种族、时间更新的 CD4+T 细胞计数和 HIV 病毒载量以及试验内的治疗组进行调整。分别分析 HLA Ⅰ类和Ⅱ类等位基因。采用 Benjamini-Hochberg 程序将假发现率限制在 5%以下（即 q 值<0.05）。
在 4829 名参与者中，有 132 例艾滋病事件、136 例慢性炎症相关疾病、167 例细菌性肺炎、45 例感染相关癌症和 49 例疱疹病毒相关艾滋病事件。发现了一些 q 值小于 0.05 的关联：HLA-DQB1∗06:04 和 HLA-DRB1∗13:02 与艾滋病相关（调整后的 HR[95%CI]分别为 2.63[1.5-4.6]和 2.25[1.4-3.7]），HLA-B∗15:17 和 HLA-DPB1∗15:01 与细菌性肺炎相关（分别为 4.93[2.3-10.7]和 4.33[2.0-9.3]），HLA-A∗69:01 与感染相关癌症相关（15.26[3.5-66.7]）。这些等位基因的携带频率为 10%或更低。
这项产生假说的研究表明，某些 HLA 等位基因可能独立于病毒载量和 CD4+T 细胞计数影响免疫功能障碍相关事件的风险。
