Data_Sheet_1_Association Between CD4/CD8 Ratio Recovery and Chronic Kidney Disease Among Human Immunodeficiency Virus-Infected Patients Receiving Antiretroviral Therapy: A 17-Year Observational Cohort Study.pdf

Background:CD4/CD8 ratio is considered as an emerging biomarker for human immunodeficiency virus (HIV)-related diseases. However, the relationship of CD4/CD8 ratio recovery and chronic kidney disease (CKD), and whether cumulative antiretroviral therapy (ART) is effective in the CD4/CD8 ratio recovery and in reducing CKD incidence among HIV patients remain unclear.
MethodsA 17-year observational cohort study was conducted on all HIV-infected patients receiving ART in Guangxi, China. Kaplan–Meier analysis was used to investigate the cumulative CKD incidence. Cox regression and propensity score matching (PSM) were used to evaluate the association between CD4/CD8 ratio recovery and CKD incidence, and the effect of ART regimens on CD4/CD8 ratio recovery and CKD incidence.
ResultsA total of 59,268 eligible individuals contributing 285,143 person-years of follow-up, with an overall CKD incidence of 9.65%. After ART, patients who developed CKD showed higher mortality than those with normal kidney function (12.48 vs. 7.57%, p < 0.001). Patients whose CD4/CD8 ratio did not recover to 0.7 had a higher CKD incidence than the patients who recovered (aHR = 2.84, 95% CI 2.63–3.07), similar to the PSM analysis (aHR = 3.13, 95% CI 2.85–3.45). Compared with the PI-based and INSTI-based regimens, NNRTI-based regimen had a better CD4/CD8 ratio recovery rate (27.04, 16.16, and 29.66%, respectively) and a lower CKD incidence (17.43, 16.16, and 7.31%, respectively).
ConclusionThis large-scale real-world setting provide new evidence that the CD4/CD8 ratio recovery is associated with lower CKD incidence in HIV-infected patients receiving ART. NNRTI-based is a better choice for CD4/CD8 ratio recovery and reducing the risk of CKD.

研究背景：CD4/CD8比值被认为是人类免疫缺陷病毒（human immunodeficiency virus, HIV）相关疾病的新兴生物标志物。然而，CD4/CD8比值恢复与慢性肾脏病（chronic kidney disease, CKD）之间的关联，以及累计抗反转录病毒治疗（antiretroviral therapy, ART）是否可促进HIV患者的CD4/CD8比值恢复，并降低其CKD发病风险，目前仍未明确。

研究方法：本研究针对中国广西地区所有接受抗反转录病毒治疗的HIV感染者，开展了一项为期17年的观察性队列研究。采用Kaplan–Meier分析探究CKD的累计发病情况；采用Cox回归分析及倾向得分匹配（propensity score matching, PSM）方法，评估CD4/CD8比值恢复与CKD发病之间的关联，以及不同ART方案对CD4/CD8比值恢复及CKD发病的影响。

研究结果：本研究共纳入59268名符合入组标准的受试者，累计随访时长达285143人年，总体CKD发病率为9.65%。接受ART治疗后，发生CKD的患者死亡率显著高于肾功能正常者（12.48% vs. 7.57%，p < 0.001）。CD4/CD8比值未恢复至0.7的患者，其CKD发病率高于比值恢复至正常水平的患者（校正后风险比（adjusted hazard ratio, aHR）=2.84，95%置信区间（confidence interval, CI）：2.63~3.07），倾向得分匹配分析得到了一致结果（aHR=3.13，95%CI：2.85~3.45）。与基于蛋白酶抑制剂（protease inhibitor, PI）和基于整合酶链转移抑制剂（integrase strand transfer inhibitor, INSTI）的治疗方案相比，基于非核苷类反转录酶抑制剂（non-nucleoside reverse transcriptase inhibitor, NNRTI）的治疗方案可获得更高的CD4/CD8比值恢复率（分别为27.04%、16.16%及29.66%），同时CKD发病率更低（分别为17.43%、16.16%及7.31%）。

研究结论：这项大规模真实世界研究为接受ART治疗的HIV感染者中，CD4/CD8比值恢复与更低的CKD发病风险相关提供了新的循证证据。基于非核苷类反转录酶抑制剂的治疗方案，是促进CD4/CD8比值恢复并降低CKD发病风险的更优选择。