HIV Epidemiology and Biostatistics Group, Research Department of Infection and Population Health, Division of Population Health, University College London Medical School, Royal Free Campus, London, UK.
AIDS. 2010 Jul 17;24(11):1667-78. doi: 10.1097/QAD.0b013e328339fe53.
Chronic kidney disease (CKD) in HIV-positive persons might be caused by both HIV and traditional or non-HIV-related factors. Our objective was to investigate long-term exposure to specific antiretroviral drugs and CKD.
A cohort study including 6843 HIV-positive persons with at least three serum creatinine measurements and corresponding body weight measurements from 2004 onwards.
CKD was defined as either confirmed (two measurements >or=3 months apart) estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m or below for persons with baseline eGFR of above 60 ml/min per 1.73 m or confirmed 25% decline in eGFR for persons with baseline eGFR of 60 ml/min per 1.73 m or less, using the Cockcroft-Gault formula. Poisson regression was used to determine factors associated with CKD.
Two hundred and twenty-five (3.3%) persons progressed to CKD during 21 482 person-years follow-up, an incidence of 1.05 per 100 person-years follow-up [95% confidence interval (CI) 0.91-1.18]; median follow-up was 3.7 years (interquartile range 2.8-5.7). After adjustment for traditional factors associated with CKD and other confounding variables, increasing cumulative exposure to tenofovir [incidence rate ratio (IRR) per year 1.16, 95% CI 1.06-1.25, P < 0.0001), indinavir (IRR 1.12, 95% CI 1.06-1.18, P < 0.0001), atazanavir (IRR 1.21, 95% CI 1.09-1.34, P = 0.0003) and lopinavir/r (IRR 1.08, 95% CI 1.01-1.16, P = 0.030) were associated with a significantly increased rate of CKD. Consistent results were observed in wide-ranging sensitivity analyses, although of marginal statistical significance for lopinavir/r. No other antiretroviral drugs were associated with increased incidence of CKD.
In this nonrandomized large cohort, increasing exposure to tenofovir was associated with a higher incidence of CKD, as was true for indinavir and atazanavir, whereas the results for lopinavir/r were less clear.
HIV 阳性个体的慢性肾脏病（CKD）可能由 HIV 以及传统或非 HIV 相关因素引起。我们的目的是研究长期暴露于特定抗逆转录病毒药物与 CKD 之间的关系。
这是一项队列研究，纳入了 6843 名 HIV 阳性个体，他们在 2004 年之后至少有 3 次血清肌酐测量值和相应的体重测量值。
CKD 的定义为：采用 Cockcroft-Gault 公式，确诊（两次测量值间隔>3 个月）肾小球滤过率（eGFR）<60 ml/min/1.73 m2 或基线 eGFR >60 ml/min/1.73 m2 的患者确诊 eGFR 下降>25%，或基线 eGFR <60 ml/min/1.73 m2 的患者确诊 eGFR 下降>25%。使用泊松回归来确定与 CKD 相关的因素。
在 21482 人年的随访期间，225 名（3.3%）患者进展为 CKD，发病率为每 100 人年 1.05 例（95%置信区间为 0.91-1.18）；中位随访时间为 3.7 年（四分位间距 2.8-5.7）。在调整了与 CKD 相关的传统因素和其他混杂变量后，与未接受替诺福韦治疗的患者相比，累积暴露于替诺福韦的时间越长（每年的发病率比[IRR]为 1.16，95%置信区间为 1.06-1.25，P<0.0001）、更易进展为 CKD，接受茚地那韦（IRR 为 1.12，95%置信区间为 1.06-1.18，P<0.0001）、阿扎那韦（IRR 为 1.21，95%置信区间为 1.09-1.34，P=0.0003）和洛匹那韦/利托那韦（IRR 为 1.08，95%置信区间为 1.01-1.16，P=0.030）治疗的患者发生 CKD 的风险也显著增加。在广泛的敏感性分析中观察到了一致的结果，尽管洛匹那韦/利托那韦的结果具有边缘统计学意义。其他抗逆转录病毒药物与 CKD 发生率的增加无关。
在这项非随机的大型队列研究中，与 CKD 发生率增加相关的是替诺福韦的累积暴露量增加，茚地那韦和阿扎那韦也是如此，而洛匹那韦/利托那韦的结果则不太明确。
