Chaplin Beth, Imade Godwin, Onwuamah Chika, Odaibo Georgina, Audu Rosemary, Okpokwu Jonathan, Olaleye David, Meloni Seema, Rawizza Holly, Muazu Mohammad, Musa Adesola Z, Samuel Jay, Agbaji Oche, Ezechi Oliver, Idigbe Emmanuel, Kanki Phyllis J
1 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health , Boston, Massachusetts.
2 Jos University Teaching Hospital , Jos, Nigeria .
AIDS Res Hum Retroviruses. 2018 Feb;34(2):228-233. doi: 10.1089/AID.2017.0198. Epub 2017 Nov 30.
Historically, in HIV patients, the K65R mutation and thymidine analogue mutations (TAMs) have been reported to rarely coexist. We retrospectively reviewed genotype data from paired samples in a cohort of HIV-1-infected Nigerian patients failing first-line antiretroviral therapies containing zidovudine (AZT) or tenofovir (TDF). Samples for each patient were taken at initial confirmed virological failure ≥1000 copies/ml (S1) and then at the latest available sample with viral load ≥1000 copies/ml before switch to second line (S2). Among 103 patients failing AZT, 19 (18.4%) had TAM-1s, 29 (28.2%) TAM-2s, and 21 (20.4%) mixed TAMs by S2. In contrast, in the 87 patients failing TDF, drug resistance mutations at S2 included K65R in 56 (64.4%), TAM-1s in 1 (1.1%), and TAM-2s in 25 patients (28.7%). Interestingly, 30.4% of patients with K65R in our study developed TAMs. These were exclusively K219E ± D67N and were not predicted to confer a resistance cost to future AZT-containing regimens.
从历史上看，在艾滋病病毒（HIV）患者中，据报道K65R突变和胸苷类似物突变（TAMs）很少同时存在。我们回顾性分析了一组感染HIV-1的尼日利亚患者的配对样本的基因型数据，这些患者一线抗逆转录病毒治疗失败，治疗方案包含齐多夫定（AZT）或替诺福韦（TDF）。每位患者的样本在初始确认病毒学失败时（病毒载量≥1000拷贝/毫升，S1）采集，然后在转换至二线治疗前病毒载量≥1000拷贝/毫升的最新可用样本时（S2）采集。在103例AZT治疗失败的患者中，到S2时，19例（18.4%）有TAM-1，29例（28.2%）有TAM-2，21例（20.4%）有混合TAMs。相比之下，在87例TDF治疗失败的患者中，S2时的耐药突变包括56例（64.4%）有K65R，1例（1.1%）有TAM-1，25例（28.7%）有TAM-2。有趣的是，在我们的研究中，30.4%的K65R患者出现了TAMs。这些均为K219E±D67N，预计不会给未来含AZT的治疗方案带来耐药成本。
