Boyd Anders, Miailhes Patrick, Lascoux-Combe Caroline, Rougier Hayette, Girard Pierre-Marie, Plaisier Emmanuelle, Lacombe Karine
INSERM, UMR_S1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
Centre de Recherche sur le Cancer de Lyon, Equipes 15 et 16, INSERM, Unité 1052, CNRS, UMR 5286, Lyon, France.
Antivir Ther. 2017;22(1):31-42. doi: 10.3851/IMP3076. Epub 2016 Aug 24.
Renal toxicity is a common side effect during tenofovir (TDF)-use in HIV-infected, but not necessarily HBV-infected, patients. Nevertheless, little is known regarding TDF-use on renal impairment during HIV-HBV coinfection. We aimed to evaluate the progression and determinants of renal impairment in coinfected patients undergoing TDF.
A total of 175 coinfected patients initiating TDF-containing antiretroviral therapy were prospectively followed. Estimated glomerular filtration rates (eGFR) were calculated at baseline and every 6-12 months. Determinants of eGRF change from baseline (ΔeGFR) were evaluated using mixed-effect linear regression and progression towards renal impairment using proportional-hazards regression.
At baseline, average eGFR was 96.7 ml/min per 1.73m (95% CI 93.8, 99.6). During a median 58.3 months (IQR 33.7-92.1) of treatment, eGFR decreased a monthly average of -0.14 ml/min per 1.73m (95% CI -0.16, -0.12). Significantly faster ΔeGFR was associated with baseline eGFR>90 (P=0.002), male gender (P=0.04), previous AIDS-defining illness at baseline (P=0.03), baseline liver cirrhosis (P=0.03) and concomitant protease inhibitor use (P=0.005). Between respective baseline and end of follow-up visits, the proportion of patients with renal impairment increased: normal function, 65.7% to 53.1%; mild impairment, 32.6% to 40.0%; moderate impairment, 1.7% to 6.9%. Higher age (P=0.01) and previous AIDS-defining illness (P=0.02) at baseline were independent risk-factors for developing impairment, while undetectable HBV DNA on-treatment was protective (P=0.006). Five (2.9%) patients permanently discontinued TDF after a renal event.
Severe HIV-related and HBV-related morbidity negatively affects renal function in coinfected patients undergoing long-term TDF. Although most patients only developed mild/moderate impairment, close renal monitoring is warranted for this particular population.
肾毒性是艾滋病毒感染患者（但不一定是乙肝病毒感染患者）使用替诺福韦（TDF）期间常见的副作用。然而，关于艾滋病毒-乙肝病毒合并感染患者使用TDF对肾功能损害的影响知之甚少。我们旨在评估接受TDF治疗的合并感染患者肾功能损害的进展情况及其决定因素。
前瞻性地随访了175例开始含TDF抗逆转录病毒治疗的合并感染患者。在基线以及每6 - 12个月计算估计肾小球滤过率（eGFR）。使用混合效应线性回归评估eGFR相对于基线的变化（ΔeGFR）的决定因素，并使用比例风险回归评估肾功能损害的进展情况。
基线时，平均eGFR为每1.73平方米96.7毫升/分钟（95%置信区间93.8, 99.6）。在中位58.3个月（四分位间距33.7 - 92.1）的治疗期间，eGFR每月平均下降-0.14毫升/分钟每1.73平方米（95%置信区间-0.16, -0.12）。ΔeGFR显著更快与基线eGFR>90（P = 0.002）、男性（P = 0.04）、基线时曾有艾滋病界定疾病（P = 0.03）、基线肝硬化（P = 0.03）以及同时使用蛋白酶抑制剂（P = 0.005）相关。在各自的基线和随访结束时，肾功能损害患者的比例增加：正常功能，从65.7%降至53.1%；轻度损害，从32.6%升至40.0%；中度损害，从1.7%升至6.9%。基线时年龄较大（P = 0.01）和曾有艾滋病界定疾病（P = 0.02）是发生肾功能损害的独立危险因素，而治疗期间乙肝病毒DNA检测不到具有保护作用（P = 0.006）。5例（2.9%）患者在发生肾脏事件后永久停用TDF。
严重的艾滋病毒相关和乙肝病毒相关疾病对接受长期TDF治疗的合并感染患者的肾功能产生负面影响。尽管大多数患者仅出现轻度/中度损害，但对于这一特定人群仍需密切监测肾功能。
