Loss of antiretroviral drug susceptibility at low viral load during early virological failure in treatment-experienced patients
Loss of antiretroviral drug susceptibility at low viral load during early virological failure in treatment-experienced patients
复制标题
经历过治疗的患者在早期病毒学失败期间，低病毒载量时抗逆转录病毒药物敏感性丧失
DOI：
10.1097/00002030-200012220-00009
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发表时间：
2000
期刊：
影响因子：
3.8
通讯作者：
C. Petropoulos
中科院分区：
文献类型：
--
作者：
N. Parkin;S. Deeks;M. T. Wrin;Joyce Yap;R. Grant;Kok H. Lee;Dorie M Heeren;N. Hellmann;C. Petropoulos
背景临床研究已经证明了二线抗逆转录病毒治疗的反应与病毒易感药物的数量之间的相关性。这些研究主要在病毒载量超过1000拷贝/ml的患者中进行。目的研究早期病毒学失败时耐药的演变，以及药敏试验在低病毒载量（低于1000拷贝/ml）患者和有治疗经验的患者中的潜在作用。方法对接受奈非那韦、沙奎那韦、阿巴卡韦和第二种核苷类逆转录酶抑制剂（NRTI）或奈韦拉平治疗的茚地那韦治疗患者进行药物敏感性和HIV-1基因型测定。结果共16例受试者。接受奈韦拉平治疗的10名受试者中有5名，接受第二种NRTI治疗的6名受试者中有1名，血浆HIV RNA达到并维持在< 500拷贝/ml。在治疗4至36周后，治疗失败的病毒对一种或多种治疗药物（包括奈非那韦和/或沙奎那韦）失去了敏感性。在10例失败中的6例中，在失败前检测到药物敏感性新降低的病毒。在至少有一份血浆样本的病毒载量在50至1000拷贝/ml之间的6例失败病例中，有5例检测到对一种或多种治疗药物的敏感性降低（病毒载量范围：260至630拷贝/ml）。结论病毒载量低于1000拷贝/ml时可检测到耐药，这可能预示着治疗失败。二线治疗方案的失败通常与HIV蛋白酶耐药性的早期演变有关。
BackgroundClinical studies have demonstrated a correlation between the response to second-line antiretroviral therapy and the number of drugs in the regimen to which the virus is susceptible. These studies have largely been performed in patients with viral loads over 1000 copies/ml. ObjectivesTo examine the evolution of resistance during early virological failure, and the potential role of susceptibility testing in patients with low viral loads (below 1000 copies/ml), in treatment-experienced patients. MethodsDrug susceptibility and genotypes of HIV-1 from indinavir-experienced patients undergoing therapy with nelfinavir, saquinavir, abacavir and either a second nucleoside reverse transcriptase inhibitor (NRTI) or nevirapine were determined. ResultsSixteen subjects were studied. Five of the ten subjects treated with nevirapine, and one of six treated with a second NRTI, achieved and maintained plasma HIV RNA < 500 copies/ml. Virus from the treatment failures lost susceptibility to one or more treatment drugs, including nelfinavir and/or saquinavir, after 4 to 36 weeks of treatment. In six of the ten failures, virus with new reductions in drug susceptibility was detected prior to failure. In five of the six failures who had at least one plasma sample with a viral load between 50 and 1000 copies/ml, reductions in susceptibility to one or more treatment drugs were detected (viral load range: 260 to 630 copies/ml). ConclusionsDrug resistance can be detected at viral loads below 1000 copies/ml which may be predictive of treatment failure. Failure of a second line regimen was typically associated with early evolution of resistance in HIV protease.