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土耳其新诊断的HIV-1阳性患者中传播的抗逆转录病毒药物耐药性突变

Transmitted antiretroviral drug resistance mutations in newly diagnosed HIV-1 positive patients in Turkey.

作者信息

Sayan Murat, Sargýn Fatma, Inan Dilara, Sevgi Dilek Yýldýz, Celikbas Aysel Kocagül, Yasar Kadriye, Kaptan Figen, Kutlu Selda Sayýn, Fýsgýn Nuriye Tasdelen, Inci Ayse, Ceran Nurgül, Karaoðlan Ylkay, Cagatay Atahan, Celen Mustafa Kemal, Koruk Suda Tekin, Ceylan Bahadýr, Yýldýrmak Taner, Akalýn Halis, Korten Volkan, Willke Ayse

机构信息

Clinical Laboratory, Kocaeli University, Kocaeli, Turkey.

Infectious Diseases, Goztepe Hospital, Medeniyet University, Istanbul, Turkey.

出版信息

J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19750. doi: 10.7448/IAS.17.4.19750. eCollection 2014.

DOI:10.7448/IAS.17.4.19750
PMID:25397495
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4225382/
Abstract

INTRODUCTION

The objective of this study was to determine the transmitted drug resistance mutations (TDRMs) in newly diagnosed HIV-1 positive patients in Turkey.

MATERIALS AND METHODS

The study was carried out between 2009 and 2014 and antiretroviral naïve 774 HIV-1 infected patients from 19 Infectious Diseases and Clinical Microbiology Departments in Turkey were included; gender: 664 (86%) male, median age: 37 (range; 1-77), median CD4+T-cell: 360 (range; 1-1320) count/mm(3), median HIV-RNA load: 2.10+E6 (range; 4.2+E2-7.41+E8) IU/mL. HIV-1 drug resistance mutations were detected by population based sequencing of the reverse transcriptase (codon 41-238) and protease (codon 1-99) domains of pol gene of HIV-1, and analyzed according to the criteria by the World Health Organization 2009 list of surveillance drug resistance mutations [1].

RESULTS

The patients had TDRMs to NRTIs (K65R, M184V), NNRTIs (K101E, K103N/S, G190A/E/S, Y181I/C, Y188H/L) and PIs (M46L, I54V, L76V, V82L/T, N83D, I84V, L90M). The prevalence of overall TDRMs was 6.7% (52/774). Resistance mutations were found to be 0.7% (6/774), 4.1% (32/774) and 2.1% (17/774) to NRTIs, NNRTIs and PIs drug groups, respectively. Three patients had NRTIs+NNRTs resistance mutations (M184V+K103N) as multi-class drug resistance. However, thymidine analogue resistance mutations (TAMs) determined two distinct genotypic profiles in the HIV-1 reverse transcriptase: TAM1: M41L, L210W and T215Y, and TAM2: D67N, K70R, K219E/Q, and T215F. The prevalence of TAM1 and TAM2 were 7.7% (60/774) and 4.3% (34/774), respectively.

CONCLUSIONS

The TDRMs prevalence of antiretroviral naïve HIV-1 infected patients may be suggested current situation of Turkey. These long-term and large-scale results show that the resistance testing must be an integral part of the management of HIV infection in Turkey.

摘要

引言

本研究的目的是确定土耳其新诊断的HIV-1阳性患者中的传播性耐药突变(TDRMs)。

材料与方法

该研究于2009年至2014年进行,纳入了来自土耳其19个传染病和临床微生物学部门的774例初治抗逆转录病毒治疗的HIV-1感染患者;性别:664例(86%)男性,年龄中位数:37岁(范围:1 - 77岁),CD4+T细胞计数中位数:360个/mm³(范围:1 - 1320个),HIV-RNA载量中位数:2.10×10⁶(范围:4.2×10² - 7.41×10⁸)IU/mL。通过对HIV-1 pol基因逆转录酶(密码子41 - 238)和蛋白酶(密码子1 - 99)结构域进行群体测序检测HIV-1耐药突变,并根据世界卫生组织2009年监测耐药突变列表的标准进行分析[1]。

结果

患者存在对核苷类逆转录酶抑制剂(NRTIs)(K65R、M184V)、非核苷类逆转录酶抑制剂(NNRTIs)(K101E、K103N/S、G190A/E/S、Y181I/C、Y188H/L)和蛋白酶抑制剂(PIs)(M46L、I54V、L76V、V82L/T、N83D、I84V、L90M)的TDRMs。总体TDRMs的患病率为6.7%(52/774)。发现对NRTIs、NNRTIs和PIs药物组的耐药突变分别为0.7%(6/774)、4.1%(32/774)和2.1%(17/774)。3例患者存在NRTIs + NNRTs耐药突变(M184V + K103N),为多类药物耐药。然而,胸苷类似物耐药突变(TAMs)在HIV-1逆转录酶中确定了两种不同的基因型谱:TAM1:M41L、L210W和T215Y,以及TAM2:D67N、K70R、K219E/Q和T215F。TAM1和TAM2的患病率分别为7.7%(60/774)和4.3%(34/774)。

结论

初治抗逆转录病毒治疗的HIV-1感染患者的TDRMs患病率可能提示了土耳其的当前情况。这些长期且大规模的结果表明,耐药检测必须成为土耳其HIV感染管理的一个组成部分。

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