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在巴西一家转诊教学中心,对其他蛋白酶抑制剂治疗失败的、多重耐药的 HIV-1 感染患者中,与 darunavir 耐药突变相关的流行情况及相关因素。

Prevalence and factors associated with darunavir resistance mutations in multi-experienced HIV-1-infected patients failing other protease inhibitors in a referral teaching center in Brazil.

机构信息

AIDS Clinic, School of Medicine, Universidade de São Paulo, São Paulo, Brazil.

出版信息

Braz J Infect Dis. 2011 May-Jun;15(3):245-8. doi: 10.1016/s1413-8670(11)70183-0.

DOI:10.1016/s1413-8670(11)70183-0
PMID:21670925
Abstract

Information about resistance profile of darunavir (DRV) is scarce in Brazil. Our objectives were to estimate the prevalence of DRV resistance mutations in patients failing protease inhibitors (PI) and to identify factors associated with having more DRV resistance mutations. All HIV-infected patients failing PI-based regimens with genotyping performed between 2007 and 2008 in a referral teaching center in São Paulo, Brazil, were included. DRV-specific resistance mutations listed by December 2008 IAS-USA panel update were considered. Two Poisson regression models were constructed to assess factors related to the presence of more DRV resistance mutations. A total of 171 HIV-infected patients with available genotyping were included. The number of patients with lopinavir, saquinavir, and amprenavir used in previous regimen were 130 (76%), 83 (49%), and 35 (20%), respectively. The prevalence of major DRV resistance mutations was 50V: 5%; 54M: 1%; 76V: 4%; 84V: 15%. For minor mutations, the rates were 11I: 3%; 32I: 7%; 33F: 23%; 47V: 6%; 54L: 6%; 74P: 3%; 89V: 6%. Only 11 (6%) of the genotypes had > 3 DRV resistance mutations. In the clinical model, time of HIV infection of > 10 years and use of amprenavir were independently associated with having more DRV resistance mutations. In the genotyping-based model, only total number of PI resistance mutations was associated with our outcome. In conclusion, the prevalence of DRV mutations was low. Time of HIV infection, use of amprenavir and total number of PI resistance mutations were associated with having more DRV mutations.

摘要

巴西有关达芦那韦(DRV)耐药谱的信息有限。我们的目的是评估在蛋白酶抑制剂(PI)治疗失败的患者中,DRV 耐药突变的流行情况,并确定与存在更多 DRV 耐药突变相关的因素。所有在巴西圣保罗的一个转诊教学中心,在 2007 年至 2008 年间进行基因分型且 PI 治疗方案失败的 HIV 感染患者均被纳入研究。仅考虑 2008 年 12 月 IAS-USA 小组更新版列出的 DRV 特异性耐药突变。构建了两个泊松回归模型来评估与存在更多 DRV 耐药突变相关的因素。共纳入 171 名可进行基因分型的 HIV 感染患者。既往方案中使用洛匹那韦、沙奎那韦和安普那韦的患者分别有 130 例(76%)、83 例(49%)和 35 例(20%)。主要 DRV 耐药突变的流行率为 50V:5%;54M:1%;76V:4%;84V:15%。对于次要突变,发生率分别为 11I:3%;32I:7%;33F:23%;47V:6%;54L:6%;74P:3%;89V:6%。只有 11 例(6%)基因型存在>3 种 DRV 耐药突变。在临床模型中,HIV 感染时间>10 年和使用安普那韦与存在更多 DRV 耐药突变独立相关。在基于基因分型的模型中,只有 PI 耐药突变总数与我们的结果相关。总之,DRV 突变的流行率较低。HIV 感染时间、安普那韦的使用和 PI 耐药突变总数与存在更多 DRV 突变相关。

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引用本文的文献

1
High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil.巴西圣保罗一项前瞻性队列研究:在有丰富抗逆转录病毒治疗经验的 HIV 感染者中,用达芦那韦/利托那韦联合优化背景治疗方案病毒学抑制率高。
Braz J Infect Dis. 2013 Jan-Feb;17(1):41-7. doi: 10.1016/j.bjid.2012.08.022. Epub 2013 Jan 5.