昆明地区HIV/HCV共感染人群基因型耐药突变的特点

Study on the Characteristics of Genotypic Drug Resistance Mutation in HIV/HCV Co-infected Population in Kunming,

目的了解云南省昆明地区接受高效抗逆转录病毒治疗(HAART)的人类免疫缺陷病毒(HIV)/丙肝病毒(HCV)共感染人群基因型耐药突变的发生情况及特点。方法收集云南省昆明地区接受HAART治疗的HIV/HCV共感染患者的临床信息及实验室资料,对病毒载量≥1 000拷贝/mL的HIV/HCV共感染患者进行基因型耐药检测,分析耐药突变位点及耐药发生情况。结果云南省昆明地区547例接受HAART治疗的HIV/HCV共感染患者中有335例患者发生病毒学失败。HAART治疗后病毒学失败的患者中发生基因型突变182例,占病毒学失败患者的54.3%(182/335),占接受HAART治疗HIV/HCV共感染患者人群的33.3%(182/547)。非核苷类反转录酶抑制剂(NNRTIs)、核苷类反转录酶抑制剂(NRTIs)以及蛋白酶类抑制剂(PIs)的突变率分别为48.6%(163/335)、36.1%(121/335)、13.4%(45/335)。NNRTIs耐药突变位点主要为K103N/S[26.6%(89/335)]、Y181C/I/V[12.5%(42/335)]、G190A/S/E[11.6%(39/335)]和V179D/E/F[12.8%(43/335];NRTIs耐药突变位点主要为M184V/I[25.7%(86/335)]和胸苷类似物突变(TAMs)(包括K70R、D67N、M41L、T215Y和K219Q)[23.0%(77/335)];PI主要出现的是次要位点L10I/V/F[9.6%(32/335)。结论当前云南省昆明地区HIV/HCV共感染患者耐药突变的存在是导致抗病毒治疗失败的主要原因,以NNRTIs的耐药突变多见,因此在HAART治疗过程中,尽早进行HIV/HCV共感染患者HIV-1耐药突变检测并及时根据耐药发生情况调整用药方案是提高抗病毒治疗效果的重要手段。

Objective To investigate the genotypical drug-resistance mutation among the HIV/HCV co-infected individuals in experiencing highly effective antiretroviral therapy in Kunming, Yunnan province . Methods The data of clinical and laboratory about antiretroviral therapy in HIV/HCV co-infected cases were collected. Then the detection of HIV genotypical drug resistance was performed for the plasmas samples whose viral load were over 1 000 copies/mL. The prevalence and the characteristics of HIV-1 drug resistance were obtained for subsequent analysis. Results A total of 335 cases suffered virological failure among 547 cases while 182 cases exhibited the resistance for antiretroviral drugs. So the resistance rate was 54.3%(182/335) and the general resistance rate 33.3%(182/547). The prevalen mutation rates of non-nucleoside reverse transcriptase(NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs)were 48.6%(163/335)、36.1%(121/335)and 13.4%(45/335)respectively. The major mutations sites of NNRTIs associated with drug resistance were K103N/S, Y181C/I/V ,G190A/S/E and V179D/E/F with the frequencies of 26.6%, 12.5%,11.6%,12.8% and 23.0%(77/335). The major resistance mutation sites of NRTIs were M184V/I [25.7%(86/335)] and thymidine analogues (TAMs)(including K70R, D67N, M41L, T215Y and K219Q)[23.0%(77/335)]. The PIs associated with drug resistance mainly showed on secondary mutations sites L10I/V/F with the frequencies of 9.6%(32/335). Conclusion The drug resistance mutations in HIV/HCV co-infected individuals are complex in Kunming, Yunnan province,and the HIV-1 drug resistance is the main cause of antiretroviral therapy failure.Therefore, to improve curative effects, it is important to test for HIV-1 drug resistance among HIV/HCV co-infected individuals and to adjust the drug regimen according to the occurrence of drug resistance.