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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics
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The paradoxical effects of using antiretroviral-based microbicides to control HIV epidemics

机译：使用基于抗逆转录病毒的杀微生物剂控制HIV流行的悖论效应

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Vaginal microbicides, designed to prevent HIV infection in women, are one of the most promising biomedical interventions. Clinical trials of second-generation microbicides have begun; if shown to be effective, they could be licensed within 5-10 years. Because these microbicides contain antiretrovirals (ARVs), they could be highly effective. However, there is concern that, if used by HIV-positive women, ARV resistance may evolve. By analyzing a mathematical model, we find that adherence could have both beneficial and detrimental effects on trial outcomes. Most importantly, we show that planned trial designs could mask resistance risks and therefore enable high-risk microbicides to pass clinical testing. We then parameterize a transmission model using epidemiological, clinical, and behavioral data to predict the consequences of wide-scale usage of high-risk microbicides in a heterosexual population. Surprisingly, we show that reducing a participant's risk of resistance during a trial could lead to unexpectedly high rates of resistance afterward when microbicides are used in public health interventions. We also find that, paradoxically, although microbicides will be used by women to protect themselves against infection, they could provide greater benefit to men. More infections in men than in women will be prevented if there is a high probability that ARVs are systemically absorbed, microbicides are less than ～50% effective, and/or adherence is less than ～60%. Men will always benefit more than women in terms of infections prevented per resistant case; but this advantage decreases as the relative fitness of drug-resistant strains increases. Interventions that use ARV-based microbicides could have surprising consequences.
机译：旨在防止妇女感染艾滋病毒的阴道杀菌剂是最有前途的生物医学干预措施之一。第二代杀菌剂的临床试验已经开始；如果证明有效，则可以在5-10年内获得许可。因为这些杀微生物剂包含抗逆转录病毒药（ARV），所以它们可能非常有效。但是，令人担忧的是，如果由HIV阳性女性使用，抗ARV可能会发展。通过分析数学模型，我们发现依从性可能对试验结果产生有利和不利影响。最重要的是，我们表明计划的试验设计可以掩盖耐药性风险，因此使高危杀菌剂能够通过临床测试。然后，我们使用流行病学，临床和行为数据对传播模型进行参数化，以预测在异性恋人群中大规模使用高风险杀微生物剂的后果。出乎意料的是，我们表明，在公共卫生干预措施中使用杀微生物剂后，降低参与者在试验期间产生抗药性的风险可能导致意外的高抗药率。我们还发现，自相矛盾的是，尽管妇女将使用杀微生物剂来保护自己免受感染，但它们可以为男人带来更大的利益。如果极有可能全身吸收ARV，杀微生物剂的有效性低于〜50％和/或依从性低于〜60％，则可以预防男性感染率高于女性感染率。就每例耐药病例所预防的感染而言，男人永远比女人受益更多；但是，随着耐药菌株相对适应性的提高，这种优势会降低。使用基于ARV的杀微生物剂进行干预可能会产生令人惊讶的后果。

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