Center for Biomedical Modeling, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA 90024, USA.
Proc Natl Acad Sci U S A. 2010 Jul 6;107(27):12381-6. doi: 10.1073/pnas.1006061107. Epub 2010 Jun 28.
The administration of antiretrovirals before HIV exposure to prevent infection (i.e., preexposure prophylaxis; PrEP) is under evaluation in clinical trials. Because PrEP is based on antiretrovirals, there is considerable concern that it could substantially increase transmitted resistance, particularly in resource-rich countries. Here we use a mathematical model to predict the effect of PrEP interventions on the HIV epidemic in the men-who-have-sex-with-men community in San Francisco. The model is calibrated using Monte Carlo filtering and analyzed by constructing nonlinear response hypersurfaces. We predict PrEP interventions could substantially reduce transmission but significantly increase the proportion of new infections caused by resistant strains. Two mechanisms can cause this increase. If risk compensation occurs, the proportion increases due to increasing transmission of resistant strains and decreasing transmission of wild-type strains. If risk behavior remains stable, the increase occurs because of reduced transmission of resistant strains coupled with an even greater reduction in transmission of wild-type strains. We define this as the paradox of PrEP (i.e., resistance appears to be increasing, but is actually decreasing). We determine this paradox is likely to occur if the efficacy of PrEP regimens against wild-type strains is greater than 30% and the relative efficacy against resistant strains is greater than 0.2 but less than the efficacy against wild-type. Our modeling shows, if risk behavior increases, that it is a valid concern that PrEP could significantly increase transmitted resistance. However, if risk behavior remains stable, we find the concern is unfounded and PrEP interventions are likely to decrease transmitted resistance.
在 HIV 暴露前给予抗逆转录病毒药物以预防感染（即暴露前预防；PrEP）正在临床试验中进行评估。由于 PrEP 基于抗逆转录病毒药物，人们非常担心它会大大增加传播的耐药性，尤其是在资源丰富的国家。在这里，我们使用数学模型来预测 PrEP 干预措施对旧金山男男性行为人群中 HIV 流行的影响。该模型使用蒙特卡罗滤波进行校准，并通过构建非线性响应超曲面进行分析。我们预测 PrEP 干预措施可以大大降低传播风险，但会显著增加耐药菌株引起的新感染比例。这种增加有两个机制。如果发生风险补偿，由于耐药株的传播增加和野生型株的传播减少，比例会增加。如果风险行为保持稳定，则由于耐药株的传播减少以及野生型株的传播减少更多，会出现增加。我们将这种情况定义为 PrEP 的悖论（即耐药性似乎在增加，但实际上在减少）。如果 PrEP 方案对野生型的疗效大于 30%，对耐药株的相对疗效大于 0.2 但小于对野生型的疗效，则我们确定这种悖论很可能发生。我们的模型表明，如果风险行为增加，PrEP 可能会显著增加传播的耐药性，这是一个合理的担忧。然而，如果风险行为保持稳定，我们发现这种担忧是没有根据的，PrEP 干预措施可能会降低传播的耐药性。
