Gervasoni Cristina, Meraviglia Paola, Landonio Simona, Baldelli Sara, Fucile Serena, Castagnoli Laura, Clementi Emilio, Riva Agostino, Galli Massimo, Rizzardini Giuliano, Cattaneo Dario
Department of Infectious Disease, L. Sacco University Hospital, Milan, Italy.
PLoS One. 2013 Dec 2;8(12):e80242. doi: 10.1371/journal.pone.0080242. eCollection 2013.
Treatment with tenofovir sometimes leads to non-reversible kidney and/or bone diseases. Factors associated with these drug-related adverse events are poorly characterized. Our objective was to investigate such factors in patients treated long term with daily tenofovir. One-hundred Caucasian HIV-positive patients with basal creatinine clearance >80 mL/min treated with tenofovir for at least 6 months and with at least one assessment of tenofovir plasma trough concentrations were considered. Tenofovir-associated adverse events were defined as the appearance of pathological proteinuria, worsening of renal function or bone demineralization. By multivariate regression analysis, we found that serum creatinine (p = 0.003) and body weight (p = 0.002) were the factors independently associated with plasma tenofovir concentrations. In particular, women with body weight<50 kg had significantly higher plasma tenofovir concentrations than those weighting >50 Kg (160±93 vs.71±52 ng/mL, p<0.001). High tenofovir plasma trough concentrations and the age of the patients were independently associated with the development of drug-related kidney and bone toxicity. In this retrospective study we have shown that HIV-infected women with low body weight are at risk to be exposed to high tenofovir plasma trough concentrations, ultimately resulting in a significant hazard to develop long-term tenofovir complications.
替诺福韦治疗有时会导致不可逆的肾脏和/或骨骼疾病。与这些药物相关不良事件相关的因素尚未得到充分描述。我们的目的是调查长期每日服用替诺福韦的患者中的此类因素。研究对象为100名白种人HIV阳性患者，其基础肌酐清除率>80 mL/min，接受替诺福韦治疗至少6个月，且至少有一次替诺福韦血浆谷浓度评估。替诺福韦相关不良事件定义为出现病理性蛋白尿、肾功能恶化或骨质脱矿。通过多因素回归分析，我们发现血清肌酐（p = 0.003）和体重（p = 0.002）是与血浆替诺福韦浓度独立相关的因素。特别是，体重<50 kg的女性血浆替诺福韦浓度显著高于体重>50 kg的女性（160±93 vs.71±52 ng/mL，p<0.001）。替诺福韦血浆谷浓度高和患者年龄与药物相关的肾脏和骨骼毒性的发生独立相关。在这项回顾性研究中，我们表明体重低的HIV感染女性有暴露于高替诺福韦血浆谷浓度的风险，最终导致发生长期替诺福韦并发症的重大风险。
