Evolution of HIV resistance mutations in patients maintained on a stable treatment regimen after virologic failure.
Evolution of HIV resistance mutations in patients maintained on a stable treatment regimen after virologic failure.
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病毒学失败后维持稳定治疗方案的患者中艾滋病毒耐药突变的演变。
DOI：
10.1097/01.qai.0000245882.28391.0c
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
O'Brien,WilliamA
中科院分区：
文献类型：
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作者：
Goetz,MatthewBidwell;Ferguson,MoniqueR;Han,Xueliang;McMillan,Greg;StClair,Marty;Pappa,KeithA;McClernon,DanielR;O'Brien,WilliamA
目的：比较在病毒学失败后继续接受胸腺嘧啶核苷类似物和/或蛋白水解酶抑制剂稳定治疗的粘附性患者的胸腺嘧啶核苷类似物突变(TAMS)和主要蛋白酶抑制物突变的出现率。设计：采用病毒学失败时有0或1个和/或0或1个主要蛋白酶抑制物耐药突变的患者的档案血浆进行随访耐药检测。结果：观察失败的中位时间为691d。胸腺嘧啶核苷类似物方案41个，蛋白水解酶抑制剂方案34个，联合利托那韦4次。新的主要蛋白水解酶抑制物突变比新的TAMs出现得更快(P=0.0019)；在不包括拉米夫定的胸腺嘧啶类似物方案中，新的TAMs出现得更快(P=0.0073)。如果拉米夫定不是胸腺嘧啶核苷类似物方案的一部分，TAMS的出现和主要的蛋白水解酶抑制物突变没有区别。在病毒学失败期间，无论是否出现新的或主要蛋白水解酶抑制物突变，或者对于胸苷类似物方案，是否使用拉米夫定，在病毒学失败期间，CD+细胞计数和血浆病毒载量(PVL)的演变都是相似的。结论：在接受拉米夫定治疗的持续性病毒学失败患者中，主要蛋白水解酶抑制物突变发生的频率和速度比TAMS更频繁、更快。
Objective:We compared the rate of emergence of thymidine analogue mutations (TAMs) and major protease inhibitor mutations in adherent patients who remained on stable treatment with a thymidine analogue and/or protease inhibitor after the onset of virologic failure.Design:Follow-up genotypic resistance testing was done using archived plasma obtained from patients having 0 or 1 TAM and/or 0 or 1 major protease inhibitor resistance mutation at the onset of virologic failure.Results:The median duration of observed failure was 691 days. There were 41 thymidine analogue regimens and 34 protease inhibitor regimens; concomitant ritonavir was used 4 times. New major protease inhibitor mutations emerged more rapidly than did new TAMs (P= 0.0019); new TAMs emerged more rapidly in thymidine analogue regimens that did not include lamivudine (P= 0.0073). The emergence of TAMs and major protease inhibitor mutations did not differ if lamivudine was not part of the thymidine analogue regimen. The evolution of CD4+ cell counts and plasma viral loads (pVLs) during virologic failure was similar regardless of whether or not a new TAM or major protease inhibitor mutations emerged or, for thymidine analogue-containing regimens, whether lamivudine was or was not used.Conclusions:Major protease inhibitor mutations arose more frequently and rapidly than did TAMs in patients with sustained virologic failure who received lamivudine.