河南某农村接受抗病毒治疗的艾滋病患者HIV-1耐药发生的六年队列分析  

Occurrence of human immunodeficiency virus-1 resistance through a six-year surveillance in ruralareas of Henan

作　　者：李韩平[1] 郭伟[1] 李宏[2] 王哲[2] 刘永健[1] 鲍作义[1] 李林[1] 庄道民[1] 刘思扬[1] 王铮[1] 王晓林[1] 李敬云[1] 

机构地区：[1]军事医学科学院微生物流行病研究所 病原微生物生物安全国家重点实验室,北京100071 [2]河南省疾病预防控制中心

出　　处：《中华医学杂志》2011年第21期1443-1447,共5页National Medical Journal of China

基　　金：国家自然科学基金（30800938、30830088）;国家“十一五”艾滋病和病毒性肝炎等重大传染病防治专项（2008ZXl0001-004）

摘　　要：目的揭示在中国农村特殊的抗病毒治疗模式下HIV．1耐药发生的规律。方法2004年3月在中国河南某农村招募75例于2003年9月开始接受齐多夫定（AZT）＋去羟肌苷（ddI）＋奈韦拉平（NVP）治疗的艾滋病患者，进行封闭式队列研究，共随访12次、788人次、历时6年3个月，每次随访均检测病毒载量及CD4细胞计数，对病毒未抑制的患者进行基因型耐药检测，采用生存分析方法分析耐药发生时问。结果患者累计病死率为16％（12／75）；共有66例发生耐药，累计耐药率为88％；生存分析发现，开始治疗的第1年，累计耐药率达到54．7％，患者不耐药的概率由100％下降到45．3％。半数患者保持对药物敏感的时间约为治疗后时间12．0个月（95％C18．6～17．0）；首次病毒载量≤4．01gU／ml和〉4．01gU／ml的两组患者，半数药物敏感的时间分别为25．1个月（95％CI19．0—33．3）和4．8个月（95％Cj4．1—5．6）。治疗过程中早发生耐药（12个月以内）的患者，病毒抑制失败和CD4细胞数下降的危险均较大。结论耐药的发生随治疗时间上升，抗病毒治疗第1年发生耐药的危险最大，病毒载量高的患者耐药发生的速度快，发生耐药对治疗的效果影响显著。初期治疗取得最大的病毒抑制是控制耐药发生的关键。Objective To analyze the occurring rules of human immunodeficiency virus （HIV） drug resistance under an unique therapy model among HIV-1 infected individuals on antiretroviral therapy （ART） in rural areas of Henan, China. Methods A cohort of 75 individuals on an ART regimen of zidovudine （ZDV） , dideoxyinosine （ddI） and nevirapine （NVP） was established in March 2003. A total of 12 surveillances were conducted and 788 person-times were studied until 2010. The parameters of CIM cell count and viral load （VL） were tested in each survey. And genotypic resistance testing was performed in patients with a failure of viral suppression. Survival analysis was used to estimate the occurrence time of resistance. Results The cumulative mortality rate was 16% （12/75）in the cohort. And the cumulative resistance rate was 88% （ 66/75 ） from 2004 to 2010. The rate of resistance reached 54. 7% and the probability from susceptibility to drugs developing resistance decreased drastically from 100% to 45.3% within the first 1 year of initiation. The occurrence time of resistance for half of individuals in the cohort was at 12.0 months （ 95 % CI 8.6 - 17. 0 ） after initiation, 25. 1 months （95 % CI 19. 0 - 33.3 ） in those whose VL was less than 4. 0 lgU/ml and 4. 8 months （ 95% CI 4. 1 - 5.6 ） at VL 〉 4.0 lgU/ml during the first investigation. The individuals with an early occurrence of resistance within 12 months carried high risks for a failure of viral suppression and a decrease of CIM counts. Conclusion The occurrence of resistance rises with the course of therapy. And the greatest probability for resistance is within the first 1 year of initial therapy. A high level of VL has a significant impact on the development of resistance. Preventing the occurrence of resistance during the initial therapy remains a key goal.

关 键 词：HIV-1 抗病毒药 抗药性 病毒 

分 类 号：R51[医药卫生—内科学]