Steegen K, Bronze M, Papathanasopoulos M A, van Zyl G, Goedhals D, Variava E, MacLeod W, Sanne I, Stevens W S, Carmona S
Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa
National Health Laboratory Service, Johannesburg, South Africa.
J Antimicrob Chemother. 2017 Jan;72(1):210-219. doi: 10.1093/jac/dkw358. Epub 2016 Sep 22.
Routine HIV-1 antiretroviral drug resistance testing for patients failing NNRTI-based regimens is not recommended in resource-limited settings. Therefore, surveys are required to monitor resistance profiles in patients failing ART.
A cross-sectional survey was conducted amongst patients failing NNRTI-based regimens in the public sector throughout South Africa. Virological failure was defined as two consecutive HIV-1 viral load results >1000 RNA copies/mL. Pol sequences were obtained using RT-PCR and Sanger sequencing and submitted to Stanford HIVdb v7.0.1.
A total of 788 sequences were available for analysis. Most patients failed a tenofovir-based NRTI backbone (74.4%) in combination with efavirenz (82.1%) after median treatment duration of 36 months. K103N (48.9%) and V106M (34.9%) were the most common NNRTI mutations. Only one-third of patients retained full susceptibility to second-generation NNRTIs such as etravirine (36.5%) and rilpivirine (27.3%). After M184V/I (82.7%), K65R was the most common NRTI mutation (45.8%). The prevalence of K65R increased to 57.5% in patients failing a tenofovir regimen without prior stavudine exposure. Cross-resistance to NRTIs was often observed, but did not seem to affect the predicted activity of zidovudine as 82.9% of patients remained fully susceptible to this drug.
The introduction of tenofovir-based first-line regimens has dramatically increased the prevalence of K65R mutations in the HIV-1-infected South African population. However, most patients failing tenofovir-based regimens remained fully susceptible to zidovudine. Based on these data, there is currently no need to change either the recommended first- or second-line ART regimens in South Africa.
在资源有限的环境中，不建议对接受基于非核苷类逆转录酶抑制剂（NNRTI）方案治疗失败的患者进行常规HIV-1抗逆转录病毒药物耐药性检测。因此，需要进行调查以监测接受抗逆转录病毒治疗（ART）失败患者的耐药情况。
在南非全国公共部门中，对接受基于NNRTI方案治疗失败的患者进行了一项横断面调查。病毒学失败定义为连续两次HIV-1病毒载量结果>1000 RNA拷贝/mL。使用逆转录聚合酶链反应（RT-PCR）和桑格测序法获得多聚酶（Pol）序列，并提交至斯坦福HIV数据库v7.0.1。
共有788个序列可供分析。大多数患者在接受中位治疗时长36个月后，基于替诺福韦的核苷类逆转录酶抑制剂（NRTI）主干方案（74.4%）联合依非韦伦（82.1%）治疗失败。K103N（48.9%）和V106M（34.9%）是最常见的NNRTI突变。只有三分之一的患者对第二代NNRTI如依曲韦林（36.5%）和利匹韦林（27.3%）仍保持完全敏感性。在M184V/I（82.7%）之后，K65R是最常见的NRTI突变（45.8%）。在未接受过司他夫定治疗而替诺福韦方案治疗失败的患者中，K65R的患病率增至57.5%。经常观察到对NRTI的交叉耐药，但似乎并不影响齐多夫定的预测活性，因为82.9%的患者对该药物仍保持完全敏感性。
在南非感染HIV-1的人群中，引入基于替诺福韦的一线方案显著增加了K65R突变的患病率。然而，大多数接受基于替诺福韦方案治疗失败的患者对齐多夫定仍保持完全敏感性。基于这些数据，目前在南非无需改变推荐的一线或二线ART方案。
