Natural polymorphisms in HIV-1 protease: Impact on effectiveness of a first-line lopinavir-containing antiretroviral therapy regimen

被引:9
作者
Champenois, Karen [1 ]
Deuffic-Burban, Sylvie [1 ,2 ]
Cotte, Laurent [3 ,4 ]
Andre, Patrice [5 ]
Choisy, Philippe [6 ]
Ajana, Faiza [6 ]
Bocket, Laurence [7 ]
Yazdanpanah, Yazdan [1 ,6 ,8 ]
机构
[1] CNRS, LEM, CRESGE, UMR 8179, F-59046 Lille, France
[2] INSERM, CTRS, U795, F-59045 Lille, France
[3] Hosp Civils Lyon, Hotel Dieu, Serv Hepatol & Gastroenterol, Lyon, France
[4] INSERM, U871, F-69008 Lyon, France
[5] Hosp Civils Lyon, Hop Croix Rousse, Virol Lab, Lyon, France
[6] Ctr Hosp Tourcoing, Serv Malad Infect & Voyageur, Tourcoing, France
[7] CHRU, Virol Lab, Lille, France
[8] Fac Med, EA 2694, Lille, France
关键词
polymorphism; HIV drug resistance; lopinavir/r; protease; baseline viral load;
D O I
10.1002/jmv.21315
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Mutations on HIV protease lead to resistance to protease inhibitors. However, resistance development may be different according to primary, secondary or polymorphic mutations. The present study was designed to assess the impact of natural protease mutations on the effectiveness of a first-line antiretroviral therapy (ART), and secondarily, their effect on the initial viral load (VL). The study was conducted in 175 HIV-1-infected patients, who initiated a first-line lopinavir/r-containing ART regimen and who had an available genotype resistance testing before initiating therapy. We assessed the association between mutations (prevalence >= 10%) and the initial VL. We assessed the association between mutations and ART effectiveness using two surrogate markers: the slope of VL decrease at I month and the time to VL undetectability. For the 175 patients, the initial median VL was 4.94 log(10) copies/ml [interquartile range: 4.44-5.47] and the initial median CD4 lymphocyte count, 219/mu l [129-296]. Eighteen mutations had a prevalence >= 10%. At 1 month, the median VL decrease was 2.35 log(10) copies/ml [1.76-2.82]. The median time to VL undetectability was 128 days [91-196]. No mutation was associated significantly with the initial VL, the slope of VL decrease at 1 month or the time to VL undetectability. This study of antiretroviral-naive patients showed that protease polymorphisms had no impact on the effectiveness of a lopinavir/r-containing ART regimen. However, polymorphisms may affect ART effectiveness differently in other populations, such as ART-experienced patients and/or patients treated with protease inhibitors other than the one used here.
引用
收藏
页码:1871 / 1879
页数:9
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