摘要
目的了解高效抗逆转录病毒治疗（HAART）失败的艾滋病患者HIV-1基因型耐药变异的情况，为临床治疗提供实验室参考数据。方法收集2008年1月至2009年12月在深圳市第三人民医院接受HAART治疗失败的41例艾滋病患者的血浆，采用RT—PCR和套式PCR从血浆中提取病毒RNA，扩增目的基因片段，并对其进行序列测定和分析。结果共获得38例抗病毒治疗失败者的基因序列，其中有3条序列显示无变异位点，在其他出现耐药变异的序列中K103N、G190A、Y181C、K101P、M184V、D67N、KTOR、T215Y及K219R为最常见的变异位点；100％（35／35）治疗失败患者出现了对非核苷类逆转录酶抑制剂NVP或EFV的高中度耐药，超过50％的患者出现了对临床上目前常用的核苷类逆转录酶抑制剂AZT、3TC、IMT及DDI的高中度耐药，仅发现极少数治疗失败患者对蛋白酶抑制剂的高中度耐药；D4T＋DDI＋NVP治疗方案是最常见出现耐药的治疗组合；病毒耐药变异往往发生在抗病毒治疗后的2～3年。结论HIV耐药变异株的出现是艾滋病患者临床上抗病毒治疗失败的主要原因，目前引起耐药突变主要是针对NNRTIs或NRTIs药物耐药，而对PIs的耐药在临床上尚比较少见，建议更换治疗组合时多考虑选用含有增强作用的PIs，从而达到更好地病毒抑制效果。
Objective This study aimed to evolution of genotypic drug resistance prevalence in treatment-failing patients in Shenzhen. Methods Peripheral venous blood samples were collected from 41 AIDS patients whom failing combination antiretroviral therapy, and were amplified by nested PCR; then the amplified fragments were sequenced and analyzed. Results Partial pol sequences of 38 samples were successfully amplified, and 3 samples have not found any mutations in their pol sequences. K103N, G190A, Y181C, KI01P, M184V, D67N, K70R, T215Y and K219 were most common mutations. According to the genotypic analysis, 100% of the patients （35/35） showed high and intermediate level resistance to nevirapine（NVP） and efavirenz （EFV）; above 50% of the patients showed high and intermediate level resistance to zidovudine（ AZT）, lamivudine（3TC）, stavudine（D4T） and didanosine （DDI） ; only a few patients showed intermediate and low level drug resistance to protease inhibitors （PIs）. Patients whom take D4T ＋ DDI ＋ NVP regimens were most common to appear drug mutation. Conclusions The high prevalence of drug resistance to NNRTIs and NRTIs among patients faling combination antiretroviral therapy in Shenzhen. That is the main reason for treatment failure in AIDS patients. Now most of mutations were detected against NNRTIs and NRTIs, only a few against PIs. Our finding suggested that a second-line antiretroviral therapy regimens is needed among the patients failing therapy and the boosted-PIs maybe are good choice.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2010年第9期584-587,共4页
National Medical Journal of China
基金
国家“十一五”艾滋病和病毒性肝炎等重大传染病防治科技重大专项（2008ZX1001-006）
2008深圳市科技研发基金深港创新圈资助计划项目[深科信（2009）37号]
