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治疗失败的HIV患者中抗逆转录病毒突变体的研究以及危险因素在病毒学失败中的作用。

Study of antiretroviral mutants in HIV patients with treatment failures and the effect of risk factors in the virological failures.

作者信息

Taylor-Castillo Lizeth, Herrera-Martínez Gisela, León-Bratti María Paz, Boza Ricardo, León-Rodríguez Bernal, Luftig Ronald B, Visoná Kirsten

机构信息

Louisiana State University, International Center for Medical Research and training, San José, Costa Rica.

出版信息

Rev Inst Med Trop Sao Paulo. 2005 Nov-Dec;47(6):327-31. doi: 10.1590/s0036-46652005000600004.

Abstract

INTRODUCTION

Information about HIV phenotypes of resistant to available ART and the influence of different risk factors on virological failures (VF) in Costa Rican HIV positive patients prior or during HAART is unknown.

MATERIALS AND METHODS

Eighty nine samples, 72 VF and 17 basal (before treatment) were analyzed by examining resistant mutants in reverse transcriptase (RT) and protease (PT) regions using Trugene or LIPA genotyping kits. Sixty eight control patients were selected and relevant information was collected in a questionnaire.

RESULTS

Poor adherence, presence of resistant mutations and number of treatment's changes were the only significant factors found (p = 0.006, 0.04 and 0.01 respectively). From 66 sequenced samples, 78%, 50% and 50% showed resistance to NRTI (nucleoside reverse transcriptase inhibitors), NNRT (non-nucleoside reverse transcriptase inhibitors) and PI (protease inhibitors), respectively. The most frequent mutations were M41L, M184V, and T215FY in RT and L62PI, L10FIRV and M36I in PT.

DISCUSSION

The most important factor related to treatment response in this study was adherence to treatment. Mutations in RT were related to the treatment failure while the ones found in PT were secondary mutations which have been previously described to influence the selection of primary resistance mutations in these regions. The study reveals the urgency to detect resistant mutations in VF to be considered by physicians for selection of treatment schedule, to analyze basal HIV patients for monitoring of the spread of resistant mutations and the importance to reinforce the adherence in the patients for overall treatment outcome.

摘要

引言

关于哥斯达黎加HIV阳性患者在接受高效抗逆转录病毒治疗(HAART)之前或期间对现有抗逆转录病毒治疗的HIV表型以及不同风险因素对病毒学失败(VF)的影响尚不清楚。

材料与方法

使用Trugene或LIPA基因分型试剂盒,通过检测逆转录酶(RT)和蛋白酶(PT)区域的耐药突变,对89份样本进行分析,其中72份为病毒学失败样本,17份为基线样本(治疗前)。选择68名对照患者,并通过问卷调查收集相关信息。

结果

发现依从性差、存在耐药突变和治疗方案变更次数是仅有的显著因素(分别为p = 0.006、0.04和0.01)。在66份测序样本中,分别有78%、50%和50%对核苷类逆转录酶抑制剂(NRTI)、非核苷类逆转录酶抑制剂(NNRT)和蛋白酶抑制剂(PI)耐药。RT区域最常见的突变是M41L、M184V和T215FY,PT区域是L62PI、L10FIRV和M36I。

讨论

本研究中与治疗反应相关的最重要因素是治疗依从性。RT区域的突变与治疗失败相关,而PT区域的突变是继发突变,此前已描述这些继发突变会影响这些区域原发耐药突变的选择。该研究揭示了检测病毒学失败中耐药突变的紧迫性,以便医生在选择治疗方案时加以考虑,分析基线HIV患者以监测耐药突变的传播,以及加强患者依从性对整体治疗结果的重要性。

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