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HIV‐1 genotype resistance pattern and evolution in patients failing nelfinavir‐containing regimens

机译:含奈非那韦治疗方案失败的患者的HIV-1基因型耐药模式及其演变

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摘要

Clinical and in vitro studies have suggested that nelfinavir (NFV)‐containing regimens may not preclude the use of other protease inhibitors (PIs) in treatment sequencing. We have studied the prevalence of 30N mutation in a human immunodeficiency virus–1 (HIV‐1)‐infected cohort and the virological response to a PI‐containing regimen in patients who had previously failed NFV. A total of 335 patients were included in the study; 32 of them were antiretroviral‐naïve and 303 were antiretroviral‐experienced (251 were PI‐experienced). Mutations 30N and/or 90M were not detected in sequences obtained either from the antiretroviral naïve or non‐PI‐experienced patients. The 30N mutation was detected in 21/251 (8.3%) of PI‐experienced patients and 90M in 103/251 (41%). Moreover, we have observed that the 88D and 77I mutations were present in more than 75% of patients harbouring the 30N HIV‐1 variant and the 71T mutation was present in almost 50% of them. Finally, mutations 30N+90M were never detected together in the same HIV‐1 strain. The 30N and 90M mutations were not observed together. The presence of mutations at positions 36, 46, 71, 77, and/or 88 in a 30N background, increases the risk of the cross‐resistance to other PIs. The use of NFV as a first‐line PI, as an application of drug sequencing strategies, may help preserve future PI options. J. Clin. Lab. Anal. 19:26–29, 2005. © 2005 Wiley‐Liss, Inc.
机译:临床和体外研究表明,含奈非那韦(NFV)的治疗方案可能并不排除在治疗测序中使用其他蛋白酶抑制剂(PI)。我们已经研究了人类免疫缺陷病毒-1(HIV-1)感染队列中30N突变的患病率,以及先前NFV失败的患者对含PI方案的病毒学应答。共有335名患者被纳入研究。其中32例未接受过抗逆转录病毒治疗,303例经历过抗逆转录病毒治疗(251例经历过PI感染)。在从未接受过抗逆转录病毒治疗或未经历过PI的患者中,未检测到30N和/或90M突变。在PI有经验的患者中,有21/251(8.3%)检测到30N突变,在103/251(41%)中检测到90M。此外,我们观察到,携带30N HIV-1变体的患者中,超过75%的患者存在88D和77I突变,其中近50%的患者存在71T突变。最后,在同一HIV-1毒株中从未一起检测到30N + 90M突变。没有一起观察到30N和90M突变。在30N背景下,位置36、46、71、77和/或88处存在突变,增加了与其他PI交叉耐药的风险。将NFV用作一线PI,以及药物测序策略的应用,可能有助于保留将来的PI选项。 J.临床实验室肛门2005年19:26-29。©2005 Wiley-Liss,Inc.

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