Department of Virology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Curr Opin Infect Dis. 2010 Dec;23(6):621-7. doi: 10.1097/QCO.0b013e32833ff1e6.
Results of trials determining if pre-exposure prophylaxis (PrEP) with antiretroviral drugs prevents transmission of HIV are expected soon. Tenofovir and emtricitabine--currently evaluated as PrEP--are popular in treatment of HIV. Drug resistance could, therefore, be critical in the use of PrEP. We review the literature regarding risks associated with drug resistance owing to PrEP.
Few studies addressed the issue of drug resistance to tenofovir and/or emtricitabine. Studies in HIV-1-infected individuals followed small numbers of patients for a short time. Studies in macaques were well designed, but used SHIV, which has an attenuated course of infection. The available information suggests that the probability of emergence of drug resistance is small. Infections that occurred despite use of PrEP had reduced peak viremia, which could reduce HIV transmissibility. Mathematical modeling suggests that, although transmitted drug resistance may under some circumstances increase, the benefits of PrEP outweigh the risks associated with resistance.
Tenofovir and emtricitabine are recommended in first-line treatment. The potentially limited impact of drug resistance should, therefore, be confirmed in daily practice. Surveillance of drug resistance is recommended in areas where PrEP is used. Patients that became infected despite use of PrEP should be closely monitored for virological failure.
即将有临床试验结果来确定抗逆转录病毒药物的暴露前预防(PrEP)是否能预防 HIV 的传播。目前正在评估的替诺福韦和恩曲他滨作为 PrEP 时具有较高的流行度。因此,耐药性可能会成为 PrEP 使用的关键问题。我们对 PrEP 相关耐药风险的文献进行了综述。
很少有研究涉及到替诺福韦和/或恩曲他滨耐药的问题。在 HIV-1 感染者中进行的研究随访了少量患者,随访时间很短。在猕猴中进行的研究设计良好,但使用了 SHIV,其感染过程较弱。现有信息表明,耐药性出现的概率很小。尽管使用了 PrEP 仍发生了感染,但其病毒血症峰值降低,这可能会降低 HIV 的传播性。数学模型表明,尽管在某些情况下,传播的耐药性可能会增加,但 PrEP 的益处超过了耐药相关的风险。
替诺福韦和恩曲他滨是一线治疗的推荐药物。因此,耐药性的潜在影响应该在日常实践中得到证实。建议在使用 PrEP 的地区进行耐药性监测。尽管使用了 PrEP 仍发生感染的患者应密切监测病毒学失败情况。