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意大利一组接受过多种抗逆转录病毒治疗的患者中,基因型指导疗法的长期益处及多核苷类耐药的流行情况。

Long-term benefit of genotypic-guided therapy and prevalence of multinucleoside resistance in an Italian group of antiretroviral multiexperienced patients.

作者信息

Quiros-Roldan E, Moretti F, Airoldi M, Fausti C, Chiodera A, Castelli F, Carosi G

机构信息

Institute of Infectious and Tropical Diseases, University of Brescia, Italy.

出版信息

J Clin Lab Anal. 2001;15(3):127-30. doi: 10.1002/jcla.1015.

Abstract

Multiple nucleoside resistance involves specific genetic changes in the HIV-1 reverse transcriptase gene, such as Q151M mutation and an insertion of two serine aminoacids at RT codon 69. Among 432 patients failing antiretroviral therapy, five (1.15%) harboured viruses with Q151M mutation into the RT gene and no viruses were identified harbouring insertion at codon 69. Also we have studied the long-term benefit of HIV genotypic testing with the failure to reach a viral load below 50 copies/ml within 1 year of antiretroviral therapy using as the primary end-point. A group of 64 HIV-positive antiretroviral multiexperienced patients were examined, all of them failing the current ART. HIV-RNA changed -0.8 log at month 4 and +0.1 log and -0.5 log at months 8 and 12, respectively. The proportion of patients with viral load below 50 copies/ml was 19.3, 32.8, and 28.1% at months 4, 8, and 12, respectively. In multidrug-experienced patients, genotype-guided therapy is not in fact able to achieve complete viral suppression in more than 30% of patients after 1 year of ART. The development of more precise resistance tests and interpretations are needed for better control of HIV replication. Other metabolic/pharmacokinetics factors of poor drug adherence should also be assessed.

摘要

多重核苷类耐药涉及HIV-1逆转录酶基因的特定基因变化,如Q151M突变以及在逆转录酶(RT)第69密码子处插入两个丝氨酸氨基酸。在432例抗逆转录病毒治疗失败的患者中,5例(1.15%)携带RT基因有Q151M突变的病毒,未发现携带第69密码子插入突变的病毒。我们还研究了以抗逆转录病毒治疗1年内未能将病毒载量降至50拷贝/毫升以下作为主要终点时,HIV基因分型检测的长期益处。对一组64例有多种抗逆转录病毒治疗经验的HIV阳性患者进行了检查,他们目前的抗逆转录病毒治疗均失败。HIV-RNA在第4个月时下降0.8 log,在第8个月和第12个月时分别上升0.1 log和下降0.5 log。病毒载量低于50拷贝/毫升的患者比例在第4、8和12个月时分别为19.3%、32.8%和28.1%。在有多种药物治疗经验的患者中,基因分型指导的治疗在抗逆转录病毒治疗1年后实际上无法使超过30%的患者实现完全病毒抑制。需要开发更精确的耐药性检测方法和解读方法,以更好地控制HIV复制。还应评估药物依从性差的其他代谢/药代动力学因素。

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