Association of age, baseline kidney function, and medication exposure with declines in creatinine clearance on pre-exposure prophylaxis: an observational cohort study.
Association of age, baseline kidney function, and medication exposure with declines in creatinine clearance on pre-exposure prophylaxis: an observational cohort study.
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DOI：
10.1016/s2352-3018(16)30153-9
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发表时间：
2016-11
期刊：
影响因子：
16.1
通讯作者：
Grant, Robert M.
中科院分区：
文献类型：
--
作者：
Gandhi, Monica;Glidden, David V.;Mayer, Kenneth;Schechter, Mauro;Buchbinder, Susan;Grinsztejn, Beatriz;Hosek, Sybil;Casapia, Martin;Guanira, Juan;Bekker, Linda-Gail;Louie, Alexander;Horng, Howard;Benet, Leslie Z.;Liu, Albert;Grant, Robert M.
随着以替诺福韦-富马酸二异丙酯/恩曲他滨(TDF/FTC)预防艾滋病毒感染的暴露前预防(PrEP)进入全球推广阶段，保持有效性但将不良反应降至最低的战略值得密切考虑。这项研究的目的是在一项大型的PrEP开放标签研究中评估肾毒性的发生率和预测因素，以帮助为这一重要预防策略的安全性监测提供指导。Iprex开放标签扩展(OLE)研究(NCT00458393)从来自巴西、厄瓜多尔、秘鲁、南非、泰国和美国的前三次PrEP试验中招募了HIV阴性的MSM/变性人参加开放标签PrEP研究。参加Iprex OLE对目前的肾功能没有限制。每12周评估一次PrEP上的肌酐清除量，其中一个子集收集头发样本，通过liquid-chromatography/tandem-mass-spectrometry.测量替诺福韦浓度计算与基线相比CrCl值的变化，并确定预测因素。Iprex-OLE(n=1224；7475人次)及其头发分研究(n=220；1114人次)参与者的基线特征相似。在72周以上(中位数)，CrCl值平均下降2.9%(p<；0.0001)，但在年龄较大的患者中下降幅度更大(−4.2%(95%CI−2.8%，−5.5%)，基线年龄40-50岁；−4.9%(−3.1%，−6.8%)，年龄≥50)。除年龄外，在多变量模型中，基线CrCl90ml/min预测肾功能下降。根据头发水平估计，三氯甲烷的减少百分比与每周服用总膳食纤维/三氟化碳的剂量之间存在单调关系(p 0.008)。随着PrEP的全球推广，我们的分析表明，安全性监测的频率可能因年龄组而异，坚持的药理学措施还可以监测毒性。国立卫生研究院
As pre-exposure prophylaxis (PrEP) with tenofovir-disoproxil-fumarate/emtricitabine (TDF/FTC) for the prevention of HIV infection enters a phase of global roll-out, strategies to maintain effectiveness, but minimize adverse effects, merit close consideration. The aim of this study was to evaluate rates and predictors of renal toxicity in a large open-label study of PrEP to help provide guidance on safety monitoring with this important prevention strategy. The iPrEx open-label-extension (OLE) study (NCT00458393) enrolled HIV-negative MSM/transgender participants from three previous PrEP trials from Brazil, Ecuador, Peru, South Africa, Thailand, and the U.S into an open-label PrEP study. There were no restrictions on current renal function for enrollment into iPrEx OLE.. Creatinine clearance (CrCl) on PrEP was estimated every 12 weeks and in a subset, hair samples were collected for measuring tenofovir (TFV)/FTC concentrations via liquid-chromatography/tandem-mass-spectrometry. Change in CrCl from baseline was calculated and predictors identified. Baseline characteristics of participants in iPrEx-OLE (n=1224; 7475 person-visits) and its hair substudy (n=220; 1114 person-visits) were similar. Over 72 weeks (median), the average decline in CrCl was −2·9% (p<0.0001), but declines were significantly greater for those starting PrEP at older ages (−4·2% (95% CI −2·8%, −5·5%), baseline age 40–50 years; −4·9% (−3·1%, −6·8%), age ≥50). Besides age, baseline CrCl of <90ml/min in multivariate models predicted renal decline. There was a monotonic relationship between percent decrease in CrCl and number of doses of TDF/FTC taken per week as estimated by hair levels (p 0.008). With the global roll-out of PrEP, our analysis suggests that the frequency of safety monitoring may differ by age group and that pharmacologic measures of adherence can additionally monitor for toxicities. NIH