南非晚期艾滋病毒感染者新冠肺炎死亡风险高：一项回顾性队列研究

摘要(中文译文)

关于HIV病毒载量抑制与免疫抑制之间关系，在合并2019冠状病毒病（COVID-19）的HIV感染者（PLHIV）中，现有文献存在相互矛盾的信息。我们评估了南非不同免疫抑制水平和病毒载量的PLHIV的院内死亡风险。我们回顾性分析了南非在世界卫生组织全球临床平台共享的个体水平队列数据，共纳入310522名住院患者，其中包括8191名接受抗逆转录病毒治疗的PLHIV。晚期疾病定义为CD4计数<200个细胞/µL。主要结局为院内死亡，定义为入院后28天内死亡。采用Royston-Parmar生存模型评估接受抗逆转录病毒治疗的PLHIV中病毒载量和CD4计数与院内死亡的关联。模型对人口学因素、COVID-19严重程度、严重急性呼吸综合征冠状病毒2变异株及合并症进行了调整。在8191名具有可用CD4和病毒载量数据的PLHIV中，77.2%实现了病毒抑制，35.9%的CD4计数<200个细胞/µL。与HIV阴性个体相比，CD4<200个细胞/µL且病毒载量≥1000拷贝/mL的PLHIV死亡风险显著更高（调整风险比[aHR] 2.73，95% CI：2.45-3.04）。在CD4<200个细胞/µL且病毒载量<1000拷贝/mL的PLHIV中（aHR 2.01，95% CI：1.84-2.20），以及CD4≥200个细胞/µL且病毒载量≥1000拷贝/mL的PLHIV中（aHR 1.47，95% CI：1.20-1.81），也观察到死亡风险升高。CD4≥200个细胞/µL且病毒抑制的PLHIV院内死亡风险最低，但仍显著升高（aHR 1.27，95% CI：1.18-1.36）。因COVID-19住院的晚期HIV疾病且病毒血症未抑制的PLHIV，其院内死亡风险大幅增加。这些发现凸显了大流行后阶段优先为PLHIV接种COVID-19疫苗和提供COVID-19治疗的重要性。然而，仍需进一步研究以了解CD4≥200个细胞/µL且病毒抑制的PLHIV死亡风险较高的原因。

Abstract

Conflicting information exists in the literature regarding the relationship between HIV viral load suppression and immune suppression among people living with HIV (PLHIV) with coronavirus disease (COVID-19) comorbidity. We evaluated risk of in-hospital mortality among PLHIV with varying levels of immunosuppression and viral load in South Africa. We analyzed retrospectively collected individual-level cohort data from South Africa shared in the World Health Organization Global Clinic Platform comprising 3,10,522 hospitalized individuals, including 8191 PLHIV on antiretroviral therapy. Advanced disease was defined as CD4 counts of <200 cells/µL. The primary outcome was in-hospital mortality, defined as death within 28 days of hospital admission. Royston-Parmar survival models were used to assess the association of viral load and CD4 counts with in-hospital mortality among PLHIV on antiretroviral therapy. Models were adjusted for demographic factors, COVID-19 severity, severe acute respiratory syndrome coronavirus-2 variants, and comorbidities. Among the 8191 PLHIV with available CD4 and viral load data, 77.2% had viral suppression, and 35.9% had CD4 counts < 200 cells/μL. Compared to HIV-negative individuals, PLHIV with CD4 < 200 cells/μL and viral load ≥1000 copies/mL had a significantly higher risk of mortality (adjusted hazard ratio [aHR] 2.73, 95% CI: 2.45-3.04). Elevated mortality risk was also observed in PLHIV with CD4 < 200 cells/μL and viral load < 1000 copies/mL (aHR 2.01, 95% CI: 1.84-2.20), and those with CD4 ≥ 200 cells/μL and viral load ≥ 1000 copies/mL (aHR 1.47, 95% CI: 1.20-1.81). PLHIV with CD4 ≥ 200 cells/μL and viral suppression had the lowest, but still significant, increased in-hospital mortality risk (aHR 1.27, 95% CI: 1.18-1.36). A substantial increased risk of in-hospital mortality occurs among PLHIV with advanced HIV disease and unsuppressed viremia hospitalized with COVID-19. These findings highlight the importance of prioritizing COVID-19 vaccination and COVID-19 therapeutics for PLHIV during the post-pandemic phase. Further research is however needed to understand the high risk of mortality in virally suppressed PLHIV with CD4 ≥ 200 cells/μL.

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