Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R
Intensification of a failing regimen with zidovudine may cause sustained virologic suppression in the presence of resensitising mutations including K65R
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DOI：
10.1016/j.jinf.2010.06.008
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发表时间：
2010-10-01
影响因子：
28.2
通讯作者：
Staszewski, S.
中科院分区：
文献类型：
--
作者：
Stephan, C.;Dauer, B.;Staszewski, S.
目的：逆转录酶（RT）突变K65R限制了进一步的治疗选择，并且是由不利的RT组合所选择的，例如替诺福韦与阿巴卡韦和/或去羟肌苷联合使用。
方法：我们从一个大型治疗队列中确定了感染人类免疫缺陷病毒1型（HIV - 1）的患者，这些患者出现病毒学失败（HIV - 1 RNA＞1000拷贝/毫升），有包括K65R在内的耐药突变证据，但在基因型耐药检测中无胸苷类似物突变（TAMs）。表型分析是利用先前收集的冷冻血浆进行的。在仅用齐多夫定强化治疗后，对患者的临床和耐药结果进行随访。
结果：5名患者在使用各种核苷类似物组合（包括阿巴卡韦、去羟肌苷、拉米夫定、奈韦拉平、依法韦仑和/或替诺福韦）进行抗逆转录病毒治疗时失败。RT序列显示K65R位点突变与其他非TAMs突变同时存在。在齐多夫定强化治疗前，患者的中位病毒载量为3.551 Log₁₀（范围3.053 - 4.681），尽管有对失败的药物方案耐药的证据，但所有患者在4周内病毒载量都降至检测不到的水平（
Objectives: The reverse transcriptase (RT)-mutation K65R limits further therapeutic options and has been selected by unfavorable RT-combinations, e.g. tenofovir in combination with abacavir and/or didanosine.Methods: We identified HIV-1 infected patients from a large treatment cohort who experienced virological failure (HIV-1 RNA >1000 copies/mL) with evidence of resistance mutations including the K65R, but without thymidine analogue mutations (TAMs) in genotypic resistance assay. Phenotype was performed from previously collected frozen plasma. The patients were followed for clinical and resistance outcome after treatment intensification with only zidovudine.Results: Five patients had experienced antiretroviral treatment failure on various nucleoside analogue combinations, containing abacavir, didanosine, lamivudine, nevirapine, reverset and/or tenofovir. RT-sequence revealed mutations at position K65R in combination with other non-TAMs. The patients' median viral load prior to zidovudine intensification was 3.551 Log10 (range 3.053-4.681) and despite evidence for resistance to the failing drug regimen, all responded within 4 weeks to undetectable levels (