浙江省2004-2007年HIV-1亚型CRF01_AE流行毒株的基因型耐药分析

摘要

Objective To study the genotypic drug-resistant mutation among treat-naive or treated patients infected with HIV-1 CRF01_AE in Zhejiang province during 2004-2007. Methods HIV-i pol amplicons (PR+RT) from 13 treated and 43 treat-naive patients were obtained by reverse transcription-polymerase chain reaction (RT-PCR). The sequences were analyzed for genotypic antiretroviral resistance through online tools (http://hivdb.stanford.edu). Results The median count of CD44+ T lymphocytes in 43treat-naive patients was 229 cells/mm3 and the median log10 viral load was 3.41. Some drug-resistant mutations were seen in these samples including amino acid 10, 46, 71, in the genes of protease (PR) and 103, 118, in the genes of reverse transcriptase (RT) whereas twenty-nine resistance mutations in the genes of PR and RT were obtained in the 13 treated patients (8/13, 61.5% ). The high prevalence of drug-resistant mutations was observed in patients who had been receiving HAART (hight active antiretroviral therapy). Among them, cross drug resistance was dominant. Correspondingly, the median counts of CD44+ T lymphocytes and the log10 viral load were 186 cells/mm3 and 3.91. Conclusion There was a low prevalence of genotypic drug-resistant mutations in treat-naive patients, but higher drug-resistant mutation in treated patients. More attention should be paid to the transmission of drug-resistant HIV strains and the antiretroviral therapy recipe should be adjusted correspondingly for the development of ART drugs, intervention as well as clinical therapy programs.%目的 了解浙江省HIV-1主要流行毒株CRF01_AE在治疗人群和未治疗人群中的基因型耐药变异情况.方法 选取2004-2007年间收集的HIV感染者样本,对HIV蛋白酶(PR)全长和部分反转录酶(RT)基因区进行RT-PCR扩增测序.分析56个感染CRF01_AE重组亚型样本的序列,其中未治疗组43例,已治疗组13例.使用Stanford HIV Drug Resistance Database(http://hivdb.stanford.edu)的在线耐药序列分析软件HIV DB进行序列分析,寻找耐药相关突变位点.结果 未治疗组CD4+T淋巴细胞中位数为229个/mm3,病毒载量log10.中位数为3.41,存在基因型耐药突变率的发生(5/43,11.6%),检出包括PR区第10、46、71位和RT区的第103、118位氨基酸的耐药相关突变;治疗组CD4+T淋巴细胞中位数为186个/mm3,病毒载量log10中位数为3.91,13例中有8例发生了基因型耐药变异(61.5%).检出29个基因型耐药突变.耐药率较高且多表现为交叉耐药.结论 浙江省未治疗的HIV感染者存在一定程度的基因型耐药突变;已开始治疗的HIV感染者基因型耐药突变发生率较高,而且交叉耐药现象广泛存在.