Pre-Exposure Prophylaxis and Antiretroviral Resistance: HIV Prevention at a Cost?
Pre-Exposure Prophylaxis and Antiretroviral Resistance: HIV Prevention at a Cost?
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DOI：
10.1093/cid/cir684
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发表时间：
2011-12-15
影响因子：
11.8
通讯作者：
Cohen, Myron S.
中科院分区：
文献类型：
--
作者：
Hurt, Christopher B.;Eron, Joseph J., Jr.;Cohen, Myron S.
暴露前预防(PrEP)，即人类免疫缺陷病毒(HIV)--未感染的个人使用抗逆转录病毒药物(ARV)防止在高风险的性行为期间感染病毒--与南非艾滋病研究方案中心(CAPRISA)004和暴露前预防倡议(IPREX)一起取得的头两项重大成功。这些成功得益于TDF2和合作伙伴PrEP试验的其他积极结果。尽管CAPRISA的两个分支的血清转换者都没有对替诺福韦产生耐药性，但Iprex的两名未被发现、血清阴性的急性艾滋病毒感染的参与者被随机分配每天服用替诺福韦-恩曲他滨，后来两人都发现了对恩曲他滨的耐药性。TDF2研究中的一个类似病例导致了对两种抗逆转录病毒药物的耐药性。这些病例促使我们检查了现有文献中关于PrEP使用的ARV引起的耐药突变的性质的文献。在这里，我们讨论PrEP选择的特征突变的影响，这些突变在日常ARV暴露中出现的速度有多快，以及ARV耐药性对个人和公共健康的影响。
Pre-exposure prophylaxis (PrEP), the use of antiretrovirals (ARVs) by human immunodeficiency virus (HIV)-uninfected individuals to prevent acquisition of the virus during high-risk sexual encounters, enjoyed its first 2 major successes with the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 and the Pre-Exposure Prophylaxis Initiative (iPrEx). These successes were buoyed by additional positive results from the TDF2 and Partners PrEP trials. Although no seroconverters in either arm of CAPRISA developed resistance to tenofovir, 2 participants in iPrEx with undetected, seronegative acute HIV infection were randomized to receive daily oral tenofovir-emtricitabine and resistance to emtricitabine was later discovered in both men. A similar case in the TDF2 study resulted in resistance to both ARVs. These cases prompted us to examine existing literature on the nature of resistance mutations elicited by ARVs used for PrEP. Here, we discuss the impact of signature mutations selected by PrEP, how rapidly these emerge with daily ARV exposure, and the individual-level and public health consequences of ARV resistance.