Prevalence of drug resistance and importance of viral load measurements in Honduran HIV-infected patients failing antiretroviral treatment

Prevalence of drug resistance and importance of viral load measurements in Honduran HIV-infected patients failing antiretroviral treatment
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DOI:
10.1111/j.1468-1293.2009.00747.x
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发表时间:
2010-02-01
期刊:
影响因子:
3
通讯作者:
Albert, J.
Albert, J.
中科院分区:
医学4区
文献类型:
--
作者:
Murillo, W.;de Rivera, I. L.;Albert, J.

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目的 洪都拉斯艾滋病毒/艾滋病项目于 2002 年开始扩大艾滋病毒治疗的覆盖范围。截至 2008 年 5 月,已有 6000 多名患者接受了联合抗逆转录病毒治疗 (cART)。由于 HIV 耐药性是有效治疗的主要障碍,本研究的目的是评估洪都拉斯 HIV-1 感染者抗逆转录病毒耐药性的患病率。 方法我们从 138 名接受 cART 治疗的个体(97 名成人和 41 名儿童)中收集了样本,这些人有治疗失败的病毒学、免疫学或临床症状。 HIV-1 pol 序列是使用内部方法获得的。根据 2007 年国际艾滋病协会 (IAS)-美国名单鉴定耐药突变,并使用 anrs 算法对 cART 的预测易感性进行评分。结果在 112 名患者 (81%) 中检测到耐药突变,其中成人 74%,儿童 98%。研究对象中分别有 27%、43% 和 11% 的三类、双类和单类耐药性。多重逻辑回归显示,耐药性与治疗失败类型[病毒学失败(比值比 (OR)=1)与免疫学失败(OR=0.11;95% 置信区间 (CI) 0.030-0.43)与临床失败(OR=0.037;95% CI 0.0063-0.22)]、传播途径(OR=42.8;95% CI)独立相关3.73-491) 和治疗年数 (OR=1.81; 95% CI 1.11-2.93)。 结论 洪都拉斯 HIV 感染者的抗逆转录病毒耐药率很高,且有治疗失败的迹象。大多数研究对象对核苷逆转录酶抑制剂、非核苷逆转录酶抑制剂和蛋白酶抑制剂表现出双重或三重耐药性。病毒学定义的治疗失败是耐药性的有力预测因素,这表明需要进行病毒载量检测来正确识别因耐药性而导致治疗失败的患者。
ObjectiveThe Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals.MethodsWe collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV-1 pol sequences were obtained using an in-house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)-USA list and predicted susceptibility to cART was scored using the anrs algorithm.ResultsResistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple-, dual- and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR)=1) vs. immunological failure (OR=0.11; 95% confidence interval (CI) 0.030-0.43) vs. clinical failure (OR=0.037; 95% CI 0.0063-0.22)], route of transmission (OR=42.8; 95% CI 3.73-491), and years on therapy (OR=1.81; 95% CI 1.11-2.93).ConclusionThe prevalence of antiretroviral resistance was high in Honduran HIV-infected patients with signs of treatment failure. A majority of study subjects showed dual- or triple-class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance.