Emergence of HIV-1 drug resistance in previously untreated patients initiating combination Antiretroviral treatment -: A comparison of different regimen types
Emergence of HIV-1 drug resistance in previously untreated patients initiating combination Antiretroviral treatment -: A comparison of different regimen types
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DOI：
10.1001/archinte.167.16.1782
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发表时间：
2007-09-10
影响因子：
--
通讯作者：
Guenthard, Huldrych F.
中科院分区：
文献类型：
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作者：
Von Wyl, Viktor;Yerly, Sabine;Guenthard, Huldrych F.
背景：针对人类免疫缺陷病毒1 （HIV-1）的标准一线联合抗逆转录病毒治疗（cART）含有非核苷类逆转录酶抑制剂（NNRTI）或利托那韦增强蛋白酶抑制剂（PI/r）。这些方案类型之间在病毒学失败后出现耐药性的程度和对进一步治疗选择的影响方面的差异很少得到评估。方法：我们调查了1999年1月1日至2005年12月31日瑞士HIV队列研究中启动cART的患者的病毒学结果，包括未增强PI、PI/r或NNRTI，并比较了这些组在治疗失败时的基因型耐药模式。结果：共有489例患者以PI开始cART， 518例为PI/r， 805例为NNRTI。共观察到177例病毒学失败，其中PI失败108例（22%），PI/r失败24例（5%），NNRTI失败45例（6%）。PI组的失败率最高（10.3 / 100人-年；95%可信区间[CI]， 8.5-12.4）。服用PI/r的患者（2.7;95% CI, 1.8-4.0）和服用NNRTI的患者（2.4;95% CI, 1.8-3.3）之间没有差异。142例（80%）病毒学治疗失败的患者可获得基因型检测结果。在接受PI治疗的患者中，84% （95% CI, 75%-92%）、30% （95% CI, 12%-54%）和66% （95% CI, 49%-80%）接受NNRTI治疗的患者中发现耐药突变（P < 0.05）。001)。多药耐药几乎完全发生在对拉米夫定-恩曲他滨和组特异性第三种药物的耐药中，在使用PI的患者中有17% (95% CI, 9%-26%)，使用PI/r的患者中有10% (95% CI, 0.1%-32%)，使用NNRTI的患者中有50% (95% CI, 33%-67%) （P < 0.05）。001)。结论：含有PI/r或NNRTI的方案与一线方案具有相似的效力。然而，在病毒学失败的情况下，使用PI/r可以减少耐药性，为未来保留更多的药物选择。
Background: Standard first-line combination antiretroviral treatment (cART) against human immunodeficiency virus 1 (HIV-1) contains either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavirboosted protease inhibitor (PI/r). Differences between these regimen types in the extent of the emergence of drug resistance on virological failure and the implications for further treatment options have rarely been assessed.Methods: We investigated virological outcomes in patients from the Swiss HIV Cohort Study initiating cART between January 1, 1999, and December 31, 2005, with an unboosted PI, a PI/r, or an NNRTI and compared genotypic drug resistance patterns among these groups at treatment failure.Results: A total of 489 patients started cART with a PI, 518 with a PI/r, and 805 with an NNRTI. A total of 177 virological failures were observed ( 108 [22%] PI failures, 24 [5%] PI/r failures, and 45 [6%] NNRTI failures). The failure rate was highest in the PI group (10.3 per 100 person-years; 95% confidence interval [CI], 8.5-12.4). No difference was seen between patients taking a PI/r (2.7; 95% CI, 1.8-4.0) and those taking an NNRTI (2.4; 95% CI, 1.8-3.3). Genotypic test results were available for 142 (80%) of the patients with a virological treatment failure. Resistance mutations were found in 84% ( 95% CI, 75%-92%) of patients taking a PI, 30% ( 95% CI, 12%-54%) of patients taking a PI/r, and 66% ( 95% CI, 49%-80%) of patients taking an NNRTI ( P < . 001). Multidrug resistance occurred almost exclusively as resistance against lamivudine-emtricitabine and the group-specific third drug and was observed in 17% ( 95% CI, 9%-26%) of patients taking a PI, 10% ( 95% CI, 0.1%-32%) of patients taking a PI/r, and 50% ( 95% CI, 33%-67%) of patients taking an NNRTI ( P < . 001).Conclusions: Regimens that contained a PI/r or an NNRTI exhibited similar potency as first-line regimens. However, the use of a PI/r led to less resistance in case of virological failure, preserving more drug options for the future.