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在接受一线高效抗逆转录病毒治疗失败的沙特感染艾滋病毒儿童中的抗逆转录病毒耐药性

Antiretroviral resistance in HIV-infected Saudi children failing first-line highly active antiretroviral therapy.

作者信息

Al Hajjar Sami Hussain, Frayha Husn, Althawadi Sahar

机构信息

Pediatric Infectious Diseases, King Faisal Specialist Hospital and Research Centre, Riyadh 11211 SaudiArabia.

出版信息

Ann Saudi Med. 2012 Nov-Dec;32(6):565-9. doi: 10.5144/0256-4947.2012.565.

Abstract

BACKGROUND AND OBJECTIVES

The use of a potent combination of antiretroviral (ARV) drugs, so-called highly active ARV therapy (HAART), has dramatically improved the quality of life and overall survival of children with human immunodeficiency virus (HIV) infection. However, these benefits can be compromised by the development of drug resistance. Our objectives were to analyze the prevalence and pattern of HIV-drug resistance among HIV-infected children failing first-line HAART.

DESIGN AND SETTING

Retrospective study based on data obtained from July 2006 through January 2009 of prevalence of genotypic resistance estimated in HAART-treated children who experienced virologic failure (HIV RNA > 1000 copies/mL) at a tertiary care center in Riyadh.

PATIENTS AND METHODS

The characteristics of the study population and genotype resistance data were analyzed in ARV-treated children who experience virologic failure.

RESULTS

Among 22 children who underwent resistance testing, the prevalence of resistance to any drug was 86.4%. Inadequate adherence to ARVs in children with drug resistance was 91%. Twenty-four mutations were detected within the protease coding region and 14 in the reverse transcriptase (RT) coding region. In 80% of isolates piM36I was detected, while rtM184V was detected in 70% of the isolates and was associated with cross-resistance to at least two nucleoside RT inhibitors (NRTI). Clinically significant non-nucleoside RT inhibitors (NNRTI) resistance was conferred by rtK103N. The best ARV susceptibility was to lopinavir in the PI class. ARV resistance was not associated with geographic regions or the CDC classification status. Study children responded satisfactorily to genotype-guided treatment and intensive family counseling.

CONCLUSION

ARVs resistance is common among HIV-infected Saudi children who experienced virologic failure to HAART. Inadequate adherence is a common cause for resistance to ARVs in children. Mutations M36I and M184V were more frequent for PIs, NRTIs and NNRTIs. Evaluation of genotype tests should be considered in all children with therapeutic failure to guide future selection of ARV regimens. These data will help improve clinical management of HIV-infected children in Saudi Arabia.

摘要

背景与目的

使用强效抗逆转录病毒(ARV)药物组合,即所谓的高效抗逆转录病毒疗法(HAART),显著改善了感染人类免疫缺陷病毒(HIV)儿童的生活质量和总体生存率。然而,耐药性的出现可能会削弱这些益处。我们的目的是分析一线HAART治疗失败的HIV感染儿童中HIV耐药性的流行情况和模式。

设计与背景

基于2006年7月至2009年1月在利雅得一家三级医疗中心接受HAART治疗且病毒学失败(HIV RNA>1000拷贝/mL)的儿童中基因型耐药性流行情况的数据进行回顾性研究。

患者与方法

对经历病毒学失败的接受ARV治疗的儿童的研究人群特征和基因型耐药性数据进行分析。

结果

在22名接受耐药性检测的儿童中,对任何药物的耐药率为86.4%。耐药儿童中抗逆转录病毒药物依从性不足的比例为91%。在蛋白酶编码区域检测到24个突变,在逆转录酶(RT)编码区域检测到14个突变。在80%的分离株中检测到piM36I,而在70%的分离株中检测到rtM184V,且其与对至少两种核苷类逆转录酶抑制剂(NRTI)的交叉耐药有关。rtK103N赋予临床上显著的非核苷类逆转录酶抑制剂(NNRTI)耐药性。在蛋白酶抑制剂(PI)类别中,对洛匹那韦的抗逆转录病毒药物敏感性最佳。抗逆转录病毒药物耐药性与地理区域或疾病控制与预防中心(CDC)分类状态无关。研究儿童对基因型指导的治疗和强化家庭咨询反应良好。

结论

在HAART治疗病毒学失败的沙特HIV感染儿童中,抗逆转录病毒药物耐药性很常见。依从性不足是儿童抗逆转录病毒药物耐药的常见原因。对于PI、NRTI和NNRTI,M36I和M184V突变更为常见。对于所有治疗失败的儿童,应考虑评估基因型检测,以指导未来抗逆转录病毒治疗方案的选择。这些数据将有助于改善沙特阿拉伯HIV感染儿童的临床管理。

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