简报：短期服用暴露前预防药物（PrEP）的依从性标志物可预测未来在大型 PrEP 示范项目中的保留情况：对即时检测药物依从性的影响。
Brief Report: Short-Term Adherence Marker to PrEP Predicts Future Nonretention in a Large PrEP Demo Project: Implications for Point-of-Care Adherence Testing.
机构信息
Division of HIV, ID, and Global Medicine, University of California, San Francisco, CA.
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.
出版信息
J Acquir Immune Defic Syndr. 2019 Jun 1;81(2):158-162. doi: 10.1097/QAI.0000000000002005.
BACKGROUND
Objective adherence metrics for tenofovir (TFV) disoproxil fumarate/emtricitabine (FTC)-based pre-exposure prophylaxis (PrEP) were critical for interpretation of efficacy in PrEP clinical trials, and there is increasing interest in using drug levels to tailor interventions for reengagement and adherence. Point-of-care immunoassays for TFV, which examine short-term adherence, are in development. However, the ability of poor short-term and long-term adherence to predict future PrEP nonretention is unknown.
SETTING
Secondary data analysis of a large, prospective multi-site U.S. PrEP demonstration project.
METHODS
An adjusted Cox-proportional hazards model examined the relationship of dried blood spot (DBS) levels of FTC-triphosphate (FTC-TP) or TFV-diphosphate (TFV-DP), measures of short-term and long-term PrEP adherence, respectively, with future study nonretention.
RESULTS
Overall, 294 individuals (median age 33 years) contributed drug levels within the U.S. PrEP demonstration project. By the end of study, 27% were lost to follow-up, 25% had at least one undetectable FTC-TP level indicating poor short-term adherence, and 29% had a drug level indicating suboptimal long-term adherence (TFV-DP <700 fmol/punch). The strongest factor associated with future study nonretention using a binary drug-level cut-off was an undetectable DBS FTC-TP level (adjusted hazard ratio 6.3; 95% confidence interval 3.8 to 10.2). The suboptimal long-term adherence based on low DBS TFV-DP levels was also associated with nonretention (adjusted hazard ratio 4.3; 95% confidence interval: 2.4 to 7.6).
CONCLUSIONS
Both short- and long-term metrics of PrEP adherence are strongly associated with future loss to follow-up in a U.S. demonstration project study. Short-term metrics of adherence, once available at the point-of-care, could be used to direct real-time tailored retention and adherence interventions.
背景
替诺福韦（TFV）双异丙酯富马酸酯/恩曲他滨（FTC）为基础的暴露前预防（PrEP）的客观依从性指标对于解释 PrEP 临床试验的疗效至关重要，并且越来越有兴趣使用药物水平来调整重新参与和依从性的干预措施。正在开发用于检查短期依从性的 TFV 即时检测免疫测定法。然而，不良短期和长期依从性预测未来 PrEP 保留率的能力尚不清楚。
地点
在美国大型前瞻性多地点 PrEP 示范项目中的二次数据分析。
方法
调整后的 Cox 比例风险模型检查了分别代表短期和长期 PrEP 依从性的干血斑（DBS）水平的 FTC-三磷酸（FTC-TP）或 TFV-二磷酸（TFV-DP）与未来研究失访之间的关系。
结果
总体而言，美国 PrEP 示范项目中共有 294 人（中位年龄 33 岁）提供了药物水平。在研究结束时，27%的人失访，25%的人至少有一个 FTC-TP 水平不可检测，表明短期依从性不良，29%的人药物水平表明长期依从性不理想（TFV-DP <700 fmol/刺）。使用二进制药物水平截止值与未来研究失访最相关的因素是 DBS FTC-TP 水平不可检测（调整后的危险比 6.3；95%置信区间 3.8 至 10.2）。基于低 DBS TFV-DP 水平的长期依从性不理想也与失访相关（调整后的危险比 4.3；95%置信区间：2.4 至 7.6）。
结论
在美国示范项目研究中，PrEP 依从性的短期和长期指标都与未来的随访损失密切相关。一旦在护理点提供了短期依从性指标，就可以用来指导实时定制的保留和依从性干预措施。
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