Factors Influencing the Emergence and Spread of HIV Drug Resistance Arising from Rollout of Antiretroviral Pre-Exposure Prophylaxis (PrEP)
Factors Influencing the Emergence and Spread of HIV Drug Resistance Arising from Rollout of Antiretroviral Pre-Exposure Prophylaxis (PrEP)
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DOI：
10.1371/journal.pone.0018165
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发表时间：
2011-04-15
期刊：
影响因子：
3.7
通讯作者：
Mellors, John W.
中科院分区：
文献类型：
--
作者：
Abbas, Ume L.;Hood, Gregory;Mellors, John W.
背景资料：抗逆转录病毒（ARV）暴露前预防（PrEP）的推出可能导致艾滋病毒耐药性的出现和传播是一个重要的公共卫生问题。我们通过数学建模研究了实施PrEP后HIV耐药流行的决定因素。方法：设计了一个模型，将年龄、性别、性活动、HIV感染状况、疾病阶段、PrEP覆盖率/停药和HIV药物敏感性等异质性纳入其中，以模拟撒哈拉以南地区流行病中PrEP对HIV预防和耐药的影响。分析表明，艾滋病毒耐药性的流行程度最受已经感染艾滋病毒的个人无意中使用PrEP的程度和持续时间的影响。影响耐药率的其他关键因素包括传播性耐药的持续时间和因PrEP感染而无意使用PrEP的持续时间。根据不确定性分析，预计10年时的中位总体耐药率为9.2%（四分位数间距为6.9%-12.2%）。一个乐观的情况下，75%的PrEP疗效，60%的易感人群的覆盖率，和5%的疏忽PrEP使用预测艾滋病毒耐药性流行率上升到10年后只有2.5%。结论：既往感染者不小心使用PrEP是HIV耐药的主要因素，不小心使用PrEP的频率和持续时间是影响HIV耐药的关键因素。PrEP推广计划应包括对艾滋病毒感染状况的常规监测，以限制耐药性的传播。
Background: The potential for emergence and spread of HIV drug resistance from rollout of antiretroviral (ARV) pre-exposure prophylaxis (PrEP) is an important public health concern. We investigated determinants of HIV drug resistance prevalence after PrEP implementation through mathematical modeling.Methodology: A model incorporating heterogeneity in age, gender, sexual activity, HIV infection status, stage of disease, PrEP coverage/discontinuation, and HIV drug susceptibility, was designed to simulate the impact of PrEP on HIV prevention and drug resistance in a sub-Saharan epidemic.Principal Findings: Analyses suggest that the prevalence of HIV drug resistance is influenced most by the extent and duration of inadvertent PrEP use in individuals already infected with HIV. Other key factors affecting drug resistance prevalence include the persistence time of transmitted resistance and the duration of inadvertent PrEP use in individuals who become infected on PrEP. From uncertainty analysis, the median overall prevalence of drug resistance at 10 years was predicted to be 9.2% (interquartile range 6.9%-12.2%). An optimistic scenario of 75% PrEP efficacy, 60% coverage of the susceptible population, and 5% inadvertent PrEP use predicts a rise in HIV drug resistance prevalence to only 2.5% after 10 years. By contrast, in a pessimistic scenario of 25% PrEP efficacy, 15% population coverage, and 25% inadvertent PrEP use, resistance prevalence increased to over 40%.Conclusions: Inadvertent PrEP use in previously-infected individuals is the major determinant of HIV drug resistance prevalence arising from PrEP. Both the rate and duration of inadvertent PrEP use are key factors. PrEP rollout programs should include routine monitoring of HIV infection status to limit the spread of drug resistance.