van der Straten Ariane, Brown Elizabeth R, Marrazzo Jeanne M, Chirenje Michael Z, Liu Karen, Gomez Kailazarid, Marzinke Mark A, Piper Jeanna M, Hendrix Craig W
Women's Global Health Imperative (WGHI) RTI International, San Francisco, CA, USA.
Center for AIDS Prevention Studies (CAPS), Department of Medicine, University of California San Francisco, San Francisco, CA, USA;
J Int AIDS Soc. 2016 Feb 4;19(1):20642. doi: 10.7448/IAS.19.1.20642. eCollection 2016.
In the Microbicide Trial Network MTN-003 (VOICE) study, a Phase IIB pre-exposure prophylaxis trial of daily oral or vaginal tenofovir (TFV), product adherence was poor based on pharmacokinetic (PK) drug detection in a random subsample. Here, we sought to compare behavioural and PK measures of adherence and examined correlates of adherence misreporting.
We included participants with PK and behavioural data from VOICE random subsample. Behavioural assessments included face-to-face interviews (FTFI), audio computer-assisted self-interviewing (ACASI) and pharmacy-returned product counts (PC). TFV concentrations < 0.31 ng/mL in plasma (oral group) and < 8.5 ng/swab in vaginal group were defined as "PK non-adherent." Logistic regression models were fit to calculate the combined predictive ability of the behavioural measures as summarized by area under the curve (AUC). Baseline characteristics associated with over-reporting daily product use relative to PK measures was assessed using a Generalized Linear Mixed Model.
In this random adherence cohort of VOICE participants assigned to active products, (N = 472), PK non-adherence was 69% in the oral group (N = 314) and 65% in the vaginal group (N = 158). Behaviourally, ≤ 10% of the cohort reported low/none use with any behavioural measure and accuracy was low (≤ 43%). None of the regression models had an AUC > 0.65 for any single or combined behavioural measures. Significant (p < 0.05) correlates of over-reporting included being very worried about getting HIV and being unmarried for the oral group; whereas for the vaginal group, being somewhat worried about HIV was associated with lower risk of over-reporting.
PK measures indicated similarly low adherence for the oral and vaginal groups. No behavioural measure accurately predicted PK non-adherence. Accurate real-time measures to monitor product adherence are urgently needed.
ClinicalTrials.gov identifier: NCT00705679.
在杀微生物剂试验网络MTN - 003（VOICE）研究中，一项每日口服或阴道用替诺福韦（TFV）的IIB期暴露前预防试验中，根据随机子样本中的药代动力学（PK）药物检测，产品依从性较差。在此，我们试图比较依从性的行为学和PK指标，并研究依从性误报的相关因素。
我们纳入了VOICE随机子样本中有PK和行为学数据的参与者。行为学评估包括面对面访谈（FTFI）、音频计算机辅助自我访谈（ACASI）和药房返还的产品计数（PC）。血浆中TFV浓度<0.31 ng/mL（口服组）和阴道拭子中<8.5 ng/拭子（阴道组）被定义为“PK不依从”。拟合逻辑回归模型以计算行为学指标的综合预测能力，以曲线下面积（AUC）总结。使用广义线性混合模型评估与相对于PK指标而言每日产品使用报告过度相关的基线特征。
在该分配至活性产品的VOICE参与者随机依从性队列中（N = 472），口服组（N = 314）的PK不依从率为69%，阴道组（N = 158）为65%。在行为学方面，≤10%的队列报告在任何行为学指标下使用量低/无，且准确性较低（≤43%）。对于任何单一或综合行为学指标，回归模型的AUC均未>0.65。报告过度的显著（p < 0.05）相关因素包括口服组中非常担心感染HIV和未婚；而对于阴道组，有点担心感染HIV与报告过度的风险较低相关。
PK指标表明口服组和阴道组的依从性同样较低。没有行为学指标能准确预测PK不依从。迫切需要准确的实时措施来监测产品依从性。
ClinicalTrials.gov标识符：NCT00705679。
