Analytic review of modeling studies of ARV Based PrEP interventions reveals strong influence of drug-resistance assumptions on the population-level effectiveness.
Analytic review of modeling studies of ARV Based PrEP interventions reveals strong influence of drug-resistance assumptions on the population-level effectiveness.
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DOI：
10.1371/journal.pone.0080927
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hallett TB
中科院分区：
文献类型：
--
作者：
Dimitrov D;Boily MC;Brown ER;Hallett TB
四项临床试验表明，基于替诺福韦的口服和局部暴露前预防（PrEP）可能有效预防艾滋病毒传播。由于所采用的假设范围广泛，因此在建模研究中，由于使用PrEP，预期的艾滋病毒传播减少和预计的耐药性流行率差异显著。我们的目标是量化预测的人口水平的影响PrEP的耐药性假设的影响。所有的建模研究，评估口服或局部PrEP的影响进行审查和耐药HIV的产生和传播机制的关键假设确定。开发了一个HIV流行的动态模型，以评估和比较口服PrEP的影响，使用从已发表的研究中提取的耐药性假设。在相同的流行病、行为和干预条件下，根据预防的新艾滋病毒感染的累积比例、艾滋病毒感染者的耐药性患病率以及耐药性传播的感染比例，评估了使用十年PrEP的益处和风险。已公布的模型表明，在阻力产生的假设和参数值的不确定性的巨大变化。根据使用的耐药参数，如果50%的人群在10年内持续使用50%有效的口服PrEP，则预计耐药患病率在2%至44%之间。我们估计，耐药性可能导致不同研究中预测的预防感染比例降低10%或高达30%。已发表的研究中使用的耐药性假设对PrEP的预期影响有很大的影响。建模者和病毒学家应合作澄清与已在使用或即将添加到抗HIV武器库中的PrEP产品生物学相关的一组耐药性假设。
Four clinical trials have shown that oral and topical pre-exposure prophylaxis (PrEP) based on tenofovir may be effective in preventing HIV transmission. The expected reduction in HIV transmission and the projected prevalence of drug resistance due to PrEP use vary significantly across modeling studies as a result of the broad spectrum of assumptions employed. Our goal is to quantify the influence of drug resistance assumptions on the predicted population-level impact of PrEP. All modeling studies which evaluate the impact of oral or topical PrEP are reviewed and key assumptions regarding mechanisms of generation and spread of drug-resistant HIV are identified. A dynamic model of the HIV epidemic is developed to assess and compare the impact of oral PrEP using resistance assumptions extracted from published studies. The benefits and risks associated with ten years of PrEP use are evaluated under identical epidemic, behavioral and intervention conditions in terms of cumulative fractions of new HIV infections prevented, resistance prevalence among those infected with HIV, and fractions of infections in which resistance is transmitted. Published models demonstrate enormous variability in resistance-generating assumptions and uncertainty in parameter values. Depending on which resistance parameterization is used, a resistance prevalence between 2% and 44% may be expected if 50% efficacious oral PrEP is used consistently by 50% of the population over ten years. We estimated that resistance may be responsible for up to a 10% reduction or up to a 30% contribution to the fraction of prevented infections predicted in different studies. Resistance assumptions used in published studies have a strong influence on the projected impact of PrEP. Modelers and virologists should collaborate toward clarifying the set of resistance assumptions biologically relevant to the PrEP products which are already in use or soon to be added to the arsenal against HIV.
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影响因子：
3.7
作者：
Abbas, Ume L.;Anderson, Roy M.;Mellors, John W.
通讯作者：
Mellors, John W.
影响因子：
56.3
作者：
Boily, Marie-Claude;Baggaley, Rebecca F.;Wang, Lei;Masse, Benoit;White, Richard G.;Hayes, Richard J.;Alary, Michel
通讯作者：
Alary, Michel
影响因子：
2
作者：
Dimitrov, Dobromir T.;Boily, Marie-Claude;Masse, Benoit
通讯作者：
Masse, Benoit
影响因子：
3.8
作者：
Morgan, D;Mahe, C;Whitworth, JAG
通讯作者：
Whitworth, JAG
南非开普敦社区和临床环境中的异性肛交。
影响因子：
3.6
作者：
Kalichman SC;Simbayi LC;Cain D;Jooste S
通讯作者：
Jooste S