估计感染时间和推断暴露前预防药物依从性的 HIV-1 遗传多样性。
HIV-1 genetic diversity to estimate time of infection and infer adherence to preexposure prophylaxis.
机构信息
aLaboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA bThailand Ministry of Public Health - U.S. Centers for Disease Control and Prevention Collaboration, Nonthaburi, Thailand cQuantitative Sciences and Data Management Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia dDepartment of Medicine, Division of Infectious Diseases, Oregon Health and Sciences University, Portland, Oregon, USA eBangkok Tenofovir Study Group, Bangkok, Thailand.
出版信息
AIDS. 2019 Dec 1;33(15):2299-2307. doi: 10.1097/QAD.0000000000002390.
OBJECTIVE
To estimate time of HIV infection in participants from the Bangkok Tenofovir Study (BTS) with daily oral tenofovir disoproxil fumarate (TDF) for preexposure prophylaxis (PrEP) and relate infection with adherence patterns.
DESIGN
We used the diversity structure of the virus population at the first HIV RNA-positive sample to estimate the date of infection, and mapped these estimates to medication diaries obtained under daily directly observed therapy (DOT).
METHODS
HIV genetic diversity was investigated in all 17 PrEP breakthrough infections and in 16 placebo recipients. We generated 10-25 HIV env sequences from each participant by single genome amplification, and calculated time since infection (and 95% confidence interval) using Poisson models of early virus evolution. Study medication diaries obtained under daily DOT were then used to compute the number of missed TDF doses at the approximate date of infection.
RESULTS
Fifteen of the 17 PrEP breakthrough infections were successfully amplified. Of these, 13 were initiated by a single genetic variant and generated reliable estimates of time since infection (median = 47 [IQR = 35] days). Eleven of these 13 were under daily DOT at the estimated time of infection. Analysis of medication diaries in these 11 participants showed 100% adherence in five, 90-95% adherence in two, 55% adherence in one, and nonadherence in three.
CONCLUSION
We estimated time of infection in participants from BTS and found several infections when high levels of adherence to TDF were reported. Our results suggest that the biological efficacy of daily TDF against parenteral HIV exposure is not 100%.
目的
估算曼谷替诺福韦研究（BTS）中每日口服替诺福韦二吡呋酯（TDF）用于暴露前预防（PrEP）的参与者的 HIV 感染时间，并将感染与用药依从模式相关联。
设计
我们使用病毒群体多样性结构在第一个 HIV RNA 阳性样本中估计感染日期，并将这些估计映射到每日直接观察治疗（DOT）下获得的用药日记中。
方法
对所有 17 例 PrEP 突破感染和 16 例安慰剂接受者的 HIV 遗传多样性进行了研究。我们通过单基因组扩增从每个参与者中生成 10-25 个 HIV env 序列，并使用早期病毒进化的泊松模型计算感染后的时间（和 95%置信区间）。然后，使用每日 DOT 下获得的研究用药日记计算在感染的大致日期漏服 TDF 剂量的数量。
结果
17 例 PrEP 突破感染中有 15 例成功扩增。其中，13 例由单个遗传变异启动，并生成了可靠的感染后时间估计（中位数=47[IQR=35]天）。这 13 例中有 11 例在感染估计时间处于每日 DOT 下。对这 11 名参与者的用药日记分析表明，5 例的依从率为 100%，2 例的依从率为 90-95%，1 例的依从率为 55%，3 例的不依从。
结论
我们估计了 BTS 参与者的感染时间，并在报告高水平 TDF 依从性时发现了几例感染。我们的结果表明，每日 TDF 对静脉内 HIV 暴露的生物学疗效并非 100%。
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