Nelson Mark R, Katlama Christine, Montaner Julio S, Cooper David A, Gazzard Brian, Clotet Bonaventura, Lazzarin Adriano, Schewe Knud, Lange Joep, Wyatt Christina, Curtis Sue, Chen Shan-Shan, Smith Stephen, Bischofberger Norbert, Rooney James F
Department of HIV and Genitourinary Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London, UK.
AIDS. 2007 Jun 19;21(10):1273-81. doi: 10.1097/QAD.0b013e3280b07b33.
To characterize the safety profile of tenofovir disoproxil fumarate (DF) for the treatment of HIV infection in adults over the first 4 years of use.
A tenofovir DF expanded access program (EAP) was initiated in 2001; safety data were examined from this program and from the manufacturer's database, which contained reports of all postmarketing adverse drug reactions received up to 30 April 2005. Specific analyses were performed to characterize the renal safety of tenofovir DF.
The EAP enrolled 10 343 patients; serious adverse events (SAEs) were reported in 631 (6%). A renal SAE of any type was observed in 0.5% of patients, and graded elevations in serum creatinine occurred in 2.2% of the patients evaluated. In a multivariate analysis, baseline risk factors for the development of increased serum creatinine on-study were elevated serum creatinine, concomitant nephrotoxic medications, low body weight, advanced age, and lower CD4 cell count. For postmarketing safety data (455 392 person-years of exposure to tenofovir DF) the most commonly reported serious adverse drug reactions were renal events, with a distribution by type similar to that observed in the EAP. Bone abnormalities were infrequently reported in either the EAP or the postmarketing safety databases. No new unexpected toxicities were identified in postmarketing safety surveillance.
The data demonstrate a favorable safety profile for tenofovir DF in the treatment of adults with HIV infection. Risk factors for development of nephrotoxicity can be identified and may be useful in managing those patients at greatest risk.
描述富马酸替诺福韦二吡呋酯（DF）在成人HIV感染治疗头4年使用中的安全性概况。
2001年启动了一项富马酸替诺福韦DF扩大可及项目（EAP）；对该项目以及制造商数据库中的安全性数据进行了检查，制造商数据库包含截至2005年4月30日收到的所有上市后药品不良反应报告。进行了特定分析以描述富马酸替诺福韦DF的肾脏安全性。
EAP纳入了10343例患者；631例（6%）报告了严重不良事件（SAE）。0.5%的患者出现了任何类型的肾脏SAE，在接受评估的患者中，2.2%出现了血清肌酐分级升高。在多变量分析中，研究期间血清肌酐升高的基线风险因素包括血清肌酐升高、同时使用肾毒性药物、低体重、高龄以及较低的CD4细胞计数。对于上市后安全性数据（455392人年的富马酸替诺福韦DF暴露），最常报告的严重药品不良反应是肾脏事件，其类型分布与EAP中观察到的相似。在EAP或上市后安全性数据库中，骨异常报告均较少。在上市后安全性监测中未发现新的意外毒性。
数据表明富马酸替诺福韦DF在治疗成人HIV感染方面具有良好的安全性概况。可以识别出肾毒性发生的风险因素，这可能有助于管理那些风险最高的患者。
