初治患者开始联合抗逆转录病毒治疗时HIV-1耐药性的出现：不同治疗方案类型的比较

Emergence of HIV-1 drug resistance in previously untreated patients initiating combination antiretroviral treatment: a comparison of different regimen types.

作者信息

von Wyl Viktor, Yerly Sabine, Böni Jürg, Bürgisser Philippe, Klimkait Thomas, Battegay Manuel, Furrer Hansjakob, Telenti Amalio, Hirschel Bernard, Vernazza Pietro L, Bernasconi Enos, Rickenbach Martin, Perrin Luc, Ledergerber Bruno, Günthard Huldrych F

机构信息

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Rämistr 100, CH-8091 Zurich, Switzerland.

出版信息

Arch Intern Med. 2007 Sep 10;167(16):1782-90. doi: 10.1001/archinte.167.16.1782.

DOI:10.1001/archinte.167.16.1782

PMID:17846398

Abstract

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 ritonavir-boosted 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.

摘要

背景

针对人类免疫缺陷病毒1型（HIV-1）的标准一线联合抗逆转录病毒治疗（cART）包含一种非核苷类逆转录酶抑制剂（NNRTI）或一种利托那韦增强的蛋白酶抑制剂（PI/r）。这些治疗方案类型在病毒学治疗失败时耐药性出现程度上的差异以及对进一步治疗选择的影响很少被评估。

方法

我们调查了瑞士HIV队列研究中在1999年1月1日至2005年12月31日期间开始接受cART治疗的患者的病毒学结局，这些患者分别接受未增强的PI、PI/r或NNRTI治疗，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例患者开始使用PI进行cART治疗，518例使用PI/r，805例使用NNRTI。共观察到177例病毒学治疗失败（108例[22%]PI治疗失败，24例[5%]PI/r治疗失败，45例[6%]NNRTI治疗失败）。PI组的失败率最高（每100人年10.3例；95%置信区间[CI]，8.5 - 12.4）。接受PI/r治疗的患者（2.7；95%CI，1.8 - 4.0）与接受NNRTI治疗的患者（2.4；95%CI，1.8 - 3.3）之间未观察到差异。142例（80%）病毒学治疗失败的患者有基因型检测结果。在接受PI治疗的患者中，84%（95%CI，75% - 92%）发现耐药突变，接受PI/r治疗的患者中为30%（95%CI，12% - 54%），接受NNRTI治疗的患者中为66%（95%CI，49% - 80%）（P <.001）。多药耐药几乎仅表现为对拉米夫定 - 恩曲他滨和特定组别的第三种药物的耐药，在接受PI治疗的患者中17%（95%CI，9% - 26%）观察到，接受PI/r治疗的患者中10%（95%CI，0.1% - 32%）观察到，接受NNRTI治疗的患者中50%（95%CI，33% - 67%）观察到（P <.001）。