Poveda Eva, de Mendoza Carmen, Martin-Carbonero Luz, Corral Angélica, Briz Verónica, González-Lahoz Juan, Soriano Vincent
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
J Antimicrob Chemother. 2007 Oct;60(4):885-8. doi: 10.1093/jac/dkm276. Epub 2007 Jul 23.
To estimate to what extent darunavir might be effective in patients failing distinct protease inhibitors (PIs), the genotypic resistance scores recently reported for the drug were examined in a large clinical HIV-1 drug resistance database.
All clinical specimens from HIV-infected patients failing PI-based regimens referred for drug resistance testing between 1999 and 2007 to a reference centre in Madrid were analysed. Darunavir-specific resistance mutations listed by the September 2006 IAS-USA panel update were considered.
A total of 1021 genotypes from patients failing lopinavir (39.2%), nelfinavir (28.1%), saquinavir (14.5%), indinavir (13.7%), atazanavir (6.6%), fosamprenavir (5.3%) and tipranavir (1.1%) were identified. The prevalence of major darunavir resistance mutations was I50V 2.1%, I54M 1.3%, L76V 2.7% and I84V 14.5%. For minor darunavir resistance mutations, the rates were V11I 3.3%, V32I 3.9%, L33F 11%, I47V 2.1%, I54L 2.3%, G73S 12.8% and L89V 2.4%. Overall, 6.7% (n = 68) of the genotypes had three or more darunavir resistance mutations, which corresponded to a mean total number of PI resistance mutations of 12.3 +/- 1.9. In the multivariate analysis, prior fosamprenavir failure, prior saquinavir failure, the total number of PI resistance mutations and the number of prior PIs used were all independently associated with having more darunavir resistance mutations.
The prevalence of darunavir resistance mutations is low in patients failing other PI-based regimens, although prior failure to amprenavir and saquinavir might produce more cross-resistance to darunavir. Thus, darunavir may be a good option for patients who have failed other PI-based regimens.
为评估达芦那韦在对不同蛋白酶抑制剂（PI）治疗失败的患者中的有效性，在一个大型临床HIV-1耐药数据库中对该药物最近报告的基因型耐药评分进行了研究。
分析了1999年至2007年间被转诊至马德里一家参考中心进行耐药性检测的、基于PI方案治疗失败的HIV感染患者的所有临床标本。采用2006年9月美国IAS小组更新列出的达芦那韦特异性耐药突变。
共鉴定出1021例对洛匹那韦（39.2%）、奈非那韦（28.1%）、沙奎那韦（14.5%）、茚地那韦（13.7%）、阿扎那韦（6.6%）、福沙普那韦（5.3%）和替拉那韦（1.1%）治疗失败患者的基因型。主要的达芦那韦耐药突变的发生率为：I50V 2.1%、I54M 1.3%、L76V 2.7%和I84V 14.5%。对于次要的达芦那韦耐药突变，发生率分别为：V11I 3.3%、V32I 3.9%、L33F 11%、I47V 2.1%、I54L 2.3%、G73S 12.8%和L89V 2.4%。总体而言，6.7%（n = 68）的基因型有三个或更多的达芦那韦耐药突变，这对应于PI耐药突变的平均总数为12.3±1.9。在多变量分析中，既往福沙普那韦治疗失败、既往沙奎那韦治疗失败、PI耐药突变的总数以及既往使用的PI的数量均与更多的达芦那韦耐药突变独立相关。
在对其他基于PI方案治疗失败的患者中，达芦那韦耐药突变的发生率较低，尽管既往氨普那韦和沙奎那韦治疗失败可能会对达芦那韦产生更多交叉耐药。因此，达芦那韦可能是对其他基于PI方案治疗失败患者的一个良好选择。
