江苏省抗病毒治疗失败HIV/AIDS患者耐药情况及基因型分析

Analysis of drug resistance and related genotypic mutations among HIV/AIDS patients who failed in antiretroviral therapy in Jiangsu province

目的分析江苏省经抗病毒治疗失败人类免疫缺陷病毒感染者和艾滋病患者(HIV/AIDS)HIV基因型耐药发生情况及特点。方法收集截至2013年12月底,治疗时间超过1年、年龄≥18岁、病毒载量≥1 000copy/mL的HIV/AIDS患者血样,采用实验室自建In-house基因扩增HIV-1pol区并进行序列分析;拼接好的序列提交美国斯坦福大学HIV耐药数据库进行比对,分析耐药基因突变及药物耐受情况。结果共纳入HIV/AIDS患者343例,280例(81.6%)pol区扩增为阳性并测序成功。扩增阳性病例基因分型,以CRF01_AE亚型为主,占58.6%(164例)。其中52.5%(147例)检出耐药位点突变,针对核苷类逆转录酶抑制剂(NRTIs)、非核苷类逆转录酶抑制剂(NNRTIs)、蛋白酶抑制剂(PIs)的耐药构成比分别为39.3%、49.6%和5.0%。针对NRTIs和NNRTIs的主要突变位点以M184V和Y181C/F/I、G190A、K103N为主,未发现针对PIs的主要位点突变,次要耐药位点突变主要为L33F、L10I。280例扩增阳性病例中,检出耐拉米夫定和耐恩曲他滨各102例(各占36.4%),耐依非韦伦133例(占47.5%),耐奈韦拉平136例(占48.6%)。结论江苏省高效抗逆转录病毒治疗失败HIV/AIDS患者耐药构成比较低,但多重耐药构成比较高。应加强随访管理,定期进行治疗效果评估、耐药检测和分析,减少耐药株的产生和传播。

Objectives To investigate prevalence and characteristics of drug resistance and genotypic mutations among HIV/AIDS patients who failed in antiretroviral therapy in Jiangsu province. Methods Blood samples of HIV/AIDS patients enrolled in HAART for more than 1 year, older than 18 years , whose virus load exceeded 1 000 copy/mL before Dec 2013 were collected for In-house amplification of HIV-1 pol coding region followed by sequence analysis . Assembled sequences were submitted to HIV drug resistance database in Stanford University for comparison , drug resistance and genotypic mutation a- nalysis. Results A total of 343 patients were enrolled, among which 280 were amplified of pol regions successfully with com- plete sequence information, resulting CRF01_AE （164 patients, accounted for 58.6%） as dominating strains. Drug resistance was detected in 147（52.5 %） patients. Corresponding drug resistance for nucleoside reverse transcriptase inhibitors （NRTIs）, non nucleoside reverse transcriptase inhibitors （NNRTIs） and protease inhibitors （PIs） accounted for 39.3%, 49.6% and 5.0%, respectively. The major drug resistant mutations to NRTIs and NNRTIs were M184V, Y181C/F/I, G190A and K103N. No major mutations were identified to PIs, while minor mutations of L33F and L10I were observed. Among 280 cases with pol amplification, drug resistance to 3TC and FTC both accounted for 36.4%, drug resistance to EFV and NVP accoun- ted for 47.50% （133 patients） and 48.6 % （136 patients） ,respectively. Conclusion Drug resistance of HIV/AIDS patients who failed HAART was low in Jiangsu province; however, multiple drug resistance phenomenon was common. Follow up manage- ment should be enhanced, treatment assessment should be performed on time and drug resistance surveillance should be strengthened to prevent emergence of drug resistant strains and reduce its spreading.