广东省HIV/AIDS患者抗病毒治疗后基因型耐药分析  

Analysis of genotypic drug resistance in HIV/AIDS patients with HAART in Guangdong Province

作　　者：兰芸[1] 蔡卫平[1] 胡凤玉[1] 唐小平[1] 戴朝霞[1] 蔡晓莉[1] 李俊彬[1] 

机构地区：[1]广州市第八人民医院,510060

出　　处：《北京医学》2013年第9期747-750,共4页Beijing Medical Journal

基　　金：十二五国家科技重大专项(2012ZX10001003-003);广州市医药卫生科技项目(20121A011077)

摘　　要：目的总结广东省261例HIV/AIDS患者抗病毒治疗1年以上,病毒未被抑制者的耐药基因型特征。方法采用实验室自建方法,进行HIV-1耐药基因型检测。构建系统进化树确定基因亚型,并通过斯坦福HIV耐药数据库在线序列分析,确定耐药突变位点及药物耐受情况。结果共检测样本280份,成功获得261条完整序列。序列分析显示:HIV-1病毒株以CRF01_AE亚型(194/261,74.3%)为主;逆转录酶(RT)区耐药位点以M184I/V(108/170,63.5%)、Y181C/V(61/170,35.9%)、K103N/S(56/170,32.9%)和G190A/S(48/170,28.2%)为主;蛋白酶(PR)区未发现主要位点突变,次要耐药位点主要为L10I/V(21/170,12.4%)和A71T/V(13/170,7.6%);未产生针对蛋白酶抑制剂(PI)的耐药;常见核苷类逆转录酶抑制剂(NRTIs)拉米夫定(3TC)、恩曲他滨(FTC)的耐药率均为43.7%,高度耐药率均为42.1%;非核苷类逆转录酶抑制剂(NNRTIs)奈韦拉平(NVP)及依非韦伦(EFV)的耐药率均为56.3%,高度耐药率分别为54.8%(143/261)和35.2%(92/261)。耐药率随着抗病毒治疗时间增长而增加,初始单一用药人群耐药率76.7%(23/30)高于初始联合用药人群耐药率54.5%(126/231)。结论广东省抗病毒治疗1年以上且病毒未抑制的HIV感染者NRTIs耐药以3TC、FTC为主,NNRTIs耐药以NVP、EFV为主。临床上应及早发现耐药更改方案以保护TDF作为二线药物的有效性;在抗病毒治疗开始时应尽量避免单一用药。Objective To investigate the characteristic of anti-HIV drug resistance of failure treatment HIV/AIDS patients in Guangdong Province who had received highly active antiretroviral therapy （HAART） for more than one year. Methods HIV-1 genotype drug resistance was detected by the IN-house method. Phylogenetic tree was constructed to confirm HIV-1 genotypes, and resistant mutations were determined and scored by the Stanford HIV Drug Resistance Database. Results A total of 280 patients was recruited in this study. Among them, 261 patients yielded positive amplified sequence results. The most common subtype strain was recombinant CRF01_AE （194/261,74.3%）. The major drug re sistant mutations in RT region were M184I/V （ 108/170,63.5% ）, Y181C/V （61/170,35.9%）, K103N/S （56/170,32.9%）and G190A/S （48/170,28.2%）. No major mutations were found in PI region, while minor mutations in PI region were L10I/V （21/170,12.4%） and A71T/V （13/170,7.6%）. The prevalences of drug resistances and high drug resistances to both 3TC and Cwere 43.7% （ 114/261 ） and 42.1% （ 110/261 ） respectively. The NNRTI drug resistances to both NVP and EFV were 56.3% （147/261） but the high drug resistances to this two drugs were 54.8% （143/261） and 35.5% （92/261） respectively. And drug resistances increased with duration of antiretroviral treatment. The drug resistance rate of patients initiated with monotherapy is 76.7%（23/30）, higher than that of those initiated with combination therapy （54.5%, 126/231 ）. Con clusion In unsuppressed HIV patients who had received more than one year HAART in Guangdong province, NRTI re-sistances were mainly to 3TC and FTC, while NNRTI resistances were mainly to NVP and EFV. Our results suggestthat more measures should be taken to find drug resistance and change the corresponding drug （s） as early as possible to protect the efficacy of second-line drug TDF, and monotherapy should be avoided at the beginning of antiviral therapy.

关 键 词：HIV AIDS 基因型耐药 抗病毒治疗 

分 类 号：R512.91[医药卫生—内科学]