HIV-1 中的耐药性。
Drug resistance in HIV-1.
机构信息
Division of Infectious Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA.
出版信息
Curr Opin Virol. 2011 Dec;1(6):582-9. doi: 10.1016/j.coviro.2011.10.020.
PURPOSE OF THE REVIEW
Changing antiretroviral regimens and the introduction of new antiretroviral drugs have altered drug resistance patterns in human immunodeficiency virus type 1 (HIV-1). This review summarizes recent information on antiretroviral drug resistance.
RECENT FINDINGS
As tenofovir and abacavir have replaced zidovudine and stavudine in antiretroviral regimens, thymidine analog resistance mutations have become less common in patients failing antiretroviral therapy in developed countries. Similarly, the near universal use of ritonavir-boosted protease inhibitors (PI) in place of unboosted PIs has made the selection of PI resistance mutations uncommon in patients failing a first-line or second-line PI regimen. The challenge of treating patients with multidrug-resistant HIV-1 has largely been addressed by the advent of newer PIs, second-generation non-nucleoside reverse transcriptase inhibitors and drugs in novel classes, including integrase inhibitors and CCR5 antagonists. Resistance to these newer agents can emerge, however, resulting in the appearance of novel drug resistance mutations in the HIV-1 polymerase, integrase and envelope genes.
SUMMARY
New drugs make possible the effective treatment of multidrug-resistant HIV-1, but the activity of these drugs may be limited by the appearance of novel drug resistance mutations.
目的综述
改变抗逆转录病毒治疗方案和引入新的抗逆转录病毒药物改变了人类免疫缺陷病毒 1 型（HIV-1）的耐药模式。本综述总结了抗逆转录病毒药物耐药性的最新信息。
最近的发现
随着替诺福韦和阿巴卡韦在抗逆转录病毒方案中取代齐多夫定和司他夫定，在发达国家接受抗逆转录病毒治疗失败的患者中，胸苷类似物耐药突变已变得不那么常见。同样，利托那韦增效蛋白酶抑制剂（PI）在未增效 PI 中的广泛应用，使得在一线或二线 PI 方案治疗失败的患者中，PI 耐药突变的选择变得不常见。由于出现了新的 PI、第二代非核苷类逆转录酶抑制剂和新型药物，包括整合酶抑制剂和 CCR5 拮抗剂，治疗对多种药物耐药的 HIV-1 患者的挑战已基本得到解决。然而，这些新药物可能会出现耐药性，导致 HIV-1 聚合酶、整合酶和包膜基因中出现新的耐药突变。
总结
新药使治疗多种药物耐药的 HIV-1 成为可能，但这些药物的活性可能受到新的耐药突变的出现限制。
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