PrEP Adherence Patterns Strongly Affect Individual HIV Risk and Observed Efficacy in Randomized Clinical Trials.
PrEP Adherence Patterns Strongly Affect Individual HIV Risk and Observed Efficacy in Randomized Clinical Trials.
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DOI：
10.1097/qai.0000000000000993
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发表时间：
2016-08-01
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影响因子：
--
通讯作者：
Donnell D
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文献类型：
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作者：
Dimitrov DT;Mâsse BR;Donnell D
随机对照试验（RCT）表明，基于替诺福韦的暴露前预防（PrEP）的疗效在很大程度上取决于PrEP使用的一致性。我们探讨了服药模式和PrEP保护的减弱可能会影响PrEP预防HIV的功效。通过数学模型模拟了一项两组RCT，假设定期、随机或大块跳过规定的每日剂量。风险驱动的依从性，其中采取的准备时，预计性，也进行了调查。研究了三种时间PrEP保护特征：长（5天），中间（3天）和短（24小时）。将建模结果与已完成的RCT中观察到的疗效进行比较。当PrEP具有长期保护特征并且仅在50%的时间内服用药丸时，预期的PrEP有效性为60%，定期为50%，随机为50%，阻滞为34%。风险驱动的服药导致29%和37%的每日服药，43%和51%的长期保护功效。在长期保护、高总体依从性和有限的阻滞服药情况下，模拟了与Partners PrEP和CDC博茨瓦纳试验中观察到的高PrEP疗效相当的PrEP疗效;在iPrEx和曼谷试验中观察到的中度疗效与随机服药和长期保护下50%依从性的情况相当。服药模式可能对PrEP提供的保护产生重大影响，即使服用相同数量的药丸。当PrEP保持保护超过一天时，服药模式可以解释PrEP RCT中观察到的广泛疗效。
Randomized controlled trials (RCT) suggest that the efficacy of tenofovir-based pre-exposure prophylaxis (PrEP) strongly depends on consistency of PrEP use. We explore how patterns of pill-taking and waning of PrEP protection may affect PrEP efficacy for HIV prevention. A two-arm RCT was simulated by mathematical models assuming that prescribed daily doses were skipped periodically, randomly or in large blocks. Risk-driven adherence, in which PrEP was taken when sex was expected, was also investigated. Three temporal PrEP protection profiles were explored: long (5 days), intermediate (3 days) and short (24 hours). Modeling results were compared to the efficacy observed in completed RCTs. Expected PrEP efficacy was 60% with periodic, 50% with random and 34% with block adherence when PrEP had a long protection profile and pills were taken only 50% of the days. Risk-driven pill-taking resulted in 29% and 37% daily pills taken and efficacy of 43% and 51% for long protection. High PrEP efficacy comparable with that observed in Partners PrEP and CDC Botswana trials was simulated under long protection, high overall adherence and limited block pill-taking; the moderate efficacy observed in iPrEx and Bangkok trials was comparable with the 50% adherence scenarios under random pill-taking and long protection. Pill-taking patterns may have a substantial impact on the protection provided by PrEP even when the same numbers of pills are taken. When PrEP retains protection for longer than a day, pill-taking patterns can explain a broad range of efficacies observed in PrEP RCTs.