摘要
目的了解我国应用高效抗逆转录病毒治疗的人类免疫缺陷病毒(HIV)感染者中耐药情况。方法收集我国上海、河南及安徽等地116份应用抗病毒治疗患者的血浆标本,采用逆转录聚合酶链反应扩增pol基因片段并进行序列测定,通过HIV耐药性数据库进行耐药相关性突变分析,并构建进化树。结果共获得44例HIV-1分离株的pol基因序列,有70%(31/44)的标本发现了针对常用的三类抗逆转录病毒药物的主要耐药性突变,其中有34%(15/44)的标本发现了针对核苷类逆转录酶抑制剂(NRTIs)的耐药性突变；有68%(30/44)的标本发现了针对非核苷类逆转录酶抑制剂(NNRTIs)的耐药性突变；仅有2%(1/44)的标本发现了对蛋白酶抑制剂(PIs)类药物的主要耐药性突变。亚型分析表明91%(40/44)为B亚型。结论在我国应用抗逆转录病毒治疗的患者中耐药性的产生已经十分严重,尤其是针对NNRTIs的高度耐药性较为突出,迫切需要应用耐药性检测进行指导。
Objective To investigate the prevalence of drug-resistant mutations in reverse transcriptase and protease coding regions in HIV infected patients treated with antiretroviral drugs （ARV）. Methods Plasma specimens were collected from 116 patients of Henan, Anhui province and Shanghai. The entire protease gene and the first 1-251 amino acids of the reverse transcriptase gene were amplified by RT-PCR from viral RNA and sequenced. The sequences were analyzed with HIV drug resistance algorithm by Stanford HIV-db program and genotypic resistance mutations were determined to particular anti-HIV drugs. Phylogenetic analysis was performed on the pol gene sequences. Results 44 pol gene sequences were obtained, and 70%（31/44） presented with virus mutations associated with resistance to at least one antiretroviral drug of the three common antiretroviral drug： nucleoside reverse transcriptase inhibitors （NRTI）, non-nucleoside reverse transcriptase inhibitors （NNRTI） and protease inhibitors （PI）. The distribution of the amino acid resistance mutations was as follows： to NRTI in 34%（15/44）; to NNRTI in 68%（30/44）; and 2%（1/44）showed PI associated major resistance. Phylogenetic analyses indicated that 91% （40/44）were B subtype. Conclusion The prevalence of drug-resistant mutations especially associated with NNRTI in HIV-1 pol gene from patients who received HAART remains to be a very serious problem, which calls for the urgent reference of drug-resistant analyses.
出处
《中华传染病杂志》
CAS
CSCD
北大核心
2006年第3期164-167,共4页
Chinese Journal of Infectious Diseases
