我国部分地区抗HIV治疗效果实验室评估和耐药变异的初步研究  

Efficacy of anti-HIV treatment and drug-resistance mutations in some parts of China

作　　者：韩晓旭[1] 张旻[1] 崔为国[2] 刘宝贵[3] 王亚男[1] 张子宁[1] 刘静[1] 耿文清[1] 刁莹莹[1] 代娣[1] 姜拥军[1] 尚红[1] 

机构地区：[1]中国医科大学附属第一医院艾滋病研究室,沈阳110001 [2]河南省疾病预防控制中心 [3]吉林省疾病预防控制中心

出　　处：《中华医学杂志》2005年第11期760-764,共5页National Medical Journal of China

基　　金：国家十五攻关课题(2001BA705B01);卫生部艾滋病防治研究资助项目(WA200301)

摘　　要：目的研究中国HIV/AIDS患者应用高效抗逆转录病毒治疗后,其病毒学、免疫学疗效以及对耐药变异的影响。方法对辽宁、吉林、河南三省HIV/AIDS患者采用三种治疗方案治疗前后进行病毒载量、CD4+T淋巴细胞数、耐药变异基因型监测。结果经HAART治疗6个月,辽宁病例病毒载量下降5.7log10拷贝/ml,有8/11的病例病毒载量达到最低检测限(LDL)以下,病毒抑制率为72.7%。吉林病例病毒载量下降幅度3.8log10拷贝/ml,有11/24的病例病毒载量达到LDL以下,病毒抑制率为45.8%。差异均有统计学意义(P<0.05)。辽宁HIV/AIDS患者治疗6个月后CD4+T淋巴淋巴细胞平均增加164个/mm3,吉林患者平均增加24个/mm3,个体差异很大。在应用逆转录酶抑制剂后有耐药变异发生,且交叉耐药、多药耐药常见。结论在应用逆转录酶抑制剂时一定要加强监测,规范化管理,及时调整用药以节省有限的药物资源并防止耐药株的传播。Objective To evaluate the Virologic and Immunologic efficacy of HAART on Chinese HIV/AIDS patients and to assess the impact of of HAART on drug resistance mutations. Methods Three cohorts of Liaoning, Jilin and Henan province received three different regimens for 6 months respectively. Regimen of Liaoning cohort comprised Efavirenz+Indinavir (EFV+IDV), regimen of Jilin cohort comprised Stavudine+ Didanosine+ Efavirenz (d4T + ddI+ EFV) and regimen of Henan cohort comprised Stavudine+ Didanosine+ Nevirapine (d4T + ddI+ NVP). Viral load, CD4+ T cell count and drug resistance genotype were detected on the three cohorts before and after treatment. Partial HIV-1 pol genes encoding protease and 1-220 amino acid of reverse transcriptase were amplified by RT-PCR and then automatically sequenced. All sequences were compared with the data of Stanford HIV Drug Resistance Database to assess resistance mutations against reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). Results During observation of 6 months, viral suppression to undetectable level and Elevated CD4+T cell count efficacy were achieved on partial Chinese HIV/AIDS patients in each of the three different regimens, even in some patients with rather low CD4+T cell count baseline. Before HAART, no primary mutations against PIs and RTIs were detected on the three cohorts, except one patient in Liaoning cohort. But after HAART, drug resistance mutations against RTIs occurred on each of the three cohorts. K103N is the most common mutation against NNRTIs, which can cause high-level resistance to each of the available NNRTIs. Y181C is another common mutation occurred in Henan cohort, which causes crossing drug resistance and multi-drug resistance to NNRTIs. In addition, intermediate level and low level resistance against NRTIs caused by K65R and L74V can also be found, but less commonly. Conclusion Treatment naive Chinese HIV/AIDS patients were sensitive to HAART. Expected virologic and immunologic efficacy of HAART were achieved on Chinese HIV/AIDS pa

关 键 词：耐药 病毒载量 HIV/AIDS患者 逆转录酶抑制剂 抗HIV 病例 LDL 果实 变异 部分地区 

分 类 号：R512.91[医药卫生—内科学] R563.1[医药卫生—临床医学]