Geretti Anna Maria, Paredes Roger, Kozal Michael J
aInstitute of Infection & Global Health, University of Liverpool, UK bHIV Unit & IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Spain cDivision of Infectious Diseases, Yale School of Medicine and VA Connecticut Healthcare System, New Haven, Connecticut, USA.
Curr Opin Infect Dis. 2015 Feb;28(1):23-30. doi: 10.1097/QCO.0000000000000136.
The review discusses new technologies for the sensitive detection of HIV drug resistance, with a focus on applications in antiretroviral treatment (ART)-naïve populations.
Conventional sequencing is well established for detecting HIV drug resistance in routine care and guides optimal treatment selection in patients starting ART. Access to conventional sequencing is nearly universal in Western countries, but remains limited in Asia, Latin America, and Africa. Technological advances now allow detection of resistance with greatly improved sensitivity compared with conventional sequencing, variably increasing the yield of resistance testing in ART-naïve populations. There is strong cumulative evidence from retrospective studies that sensitive detection of resistant mutants in baseline plasma samples lacking resistance by conventional sequencing more than doubles the risk of virological failure after starting efavirenz-based or nevirapine-based ART.
Sensitive resistance testing methods are mainly confined to research applications and in this context have provided great insight into the dynamics of drug resistance development, persistence, and transmission. Adoption in care settings is becoming increasingly possible, although important challenges remain. Platforms for diagnostic use must undergo technical improvements to ensure good performance and ease of use, and clinical validation is required to ensure utility.
本综述探讨了用于灵敏检测HIV耐药性的新技术，重点关注在初治抗逆转录病毒治疗（ART）人群中的应用。
常规测序在常规护理中检测HIV耐药性方面已得到广泛应用，并指导开始接受ART治疗的患者进行最佳治疗选择。在西方国家，几乎普遍都能进行常规测序，但在亚洲、拉丁美洲和非洲，其应用仍然有限。与常规测序相比，技术进步现在能够以更高的灵敏度检测耐药性，不同程度地提高了初治ART人群中耐药性检测的阳性率。回顾性研究有强有力的累积证据表明，通过常规测序在缺乏耐药性的基线血浆样本中灵敏检测耐药突变体，会使基于依非韦伦或奈韦拉平的ART治疗开始后病毒学失败的风险增加一倍以上。
灵敏的耐药性检测方法主要局限于研究应用，在这方面为耐药性发展、持续存在和传播的动态变化提供了深刻见解。尽管仍然存在重大挑战，但在护理环境中的应用正变得越来越可行。用于诊断的平台必须进行技术改进以确保良好性能和易用性，并且需要进行临床验证以确保其效用。
