University Hospital Zürich and Institute of Medical Virology, University of Zurich, Switzerland.
Pierre et Marie Curie University and Pitié-Salpêtriere Hospital, Paris, France.
Clin Infect Dis. 2019 Jan 7;68(2):177-187. doi: 10.1093/cid/ciy463.
Contemporary antiretroviral therapies (ART) and management strategies have diminished both human immunodeficiency virus (HIV) treatment failure and the acquired resistance to drugs in resource-rich regions, but transmission of drug-resistant viruses has not similarly decreased. In low- and middle-income regions, ART roll-out has improved outcomes, but has resulted in increasing acquired and transmitted resistances. Our objective was to review resistance to ART drugs and methods to detect it, and to provide updated recommendations for testing and monitoring for drug resistance in HIV-infected individuals.
A volunteer panel of experts appointed by the International Antiviral (formerly AIDS) Society-USA reviewed relevant peer-reviewed data that were published or presented at scientific conferences. Recommendations were rated according to the strength of the recommendation and quality of the evidence, and reached by full panel consensus.
Resistance testing remains a cornerstone of ART. It is recommended in newly-diagnosed individuals and in patients in whom ART has failed. Testing for transmitted integrase strand-transfer inhibitor resistance is currently not recommended, but this may change as more resistance emerges with widespread use. Sanger-based and next-generation sequencing approaches are each suited for genotypic testing. Testing for minority variants harboring drug resistance may only be considered if treatments depend on a first-generation nonnucleoside analogue reverse transcriptase inhibitor. Different HIV-1 subtypes do not need special considerations regarding resistance testing.
Testing for HIV drug resistance in drug-naive individuals and in patients in whom antiretroviral drugs are failing, and the appreciation of the role of testing, are crucial to the prevention and management of failure of ART.
当代抗逆转录病毒疗法(ART)和管理策略不仅减少了资源丰富地区的人类免疫缺陷病毒(HIV)治疗失败和对药物的获得性耐药,而且耐药病毒的传播也没有相应减少。在中低收入地区,ART 的推出改善了治疗效果,但导致获得性和传播性耐药性的增加。我们的目的是审查抗逆转录病毒药物的耐药性及其检测方法,并为 HIV 感染者的耐药性检测和监测提供最新的建议。
由国际抗病毒学会-美国(前身为艾滋病学会)任命的一个志愿者专家小组审查了发表或在科学会议上提交的相关同行评议数据。建议根据推荐的强度和证据的质量进行分级,并通过全体小组成员的共识达成。
耐药性检测仍然是 ART 的基石。建议在新诊断的个体和 ART 治疗失败的患者中进行检测。目前不建议检测传播的整合酶链转移抑制剂耐药性,但随着广泛使用耐药性的增加,这种情况可能会改变。基于 Sanger 的测序和下一代测序方法都适用于基因型检测。只有在治疗依赖第一代非核苷类逆转录酶抑制剂时,才可以考虑检测携带耐药性的少数变异体。不同的 HIV-1 亚型在耐药性检测方面不需要特殊考虑。
在未接受药物治疗的个体和接受抗逆转录病毒药物治疗失败的患者中进行 HIV 耐药性检测,以及认识到检测的作用,对于预防和管理 ART 失败至关重要。