河南省商丘市艾滋病抗病毒治疗病毒未抑制患者HIV-1耐药毒株的变异*
Genotype resistant mutations among patients failed to high antiretroviral therapy in Henan Province

目的:了解河南省商丘市艾滋病一线抗病毒治疗病毒未抑制患者HIV-1耐药毒株的变异。方法:采集河南省商丘市一线抗病毒治疗大于6个月、病毒未抑制的艾滋病患者血样231份,提取RNA,通过逆转录及巢式PCR扩增HIV-1 pol区基因,所得扩增片段进行测序后提交斯坦福大学HIV耐药数据库进行基因型耐药性分析。结果:在231份样本中,229份扩增并测序成功,共获得229例患者蛋白酶区和逆转录酶区的基因扩增片段。针对非核苷类逆转录酶抑制剂(NNRTIs)、核苷类逆转录酶抑制剂(NRTIs)和蛋白酶抑制剂(PIs),分别有185例(80.79%)、150例(65.50%)和3例(1.31%)发生耐药性突变,针对上述各抑制剂发生最多的耐药性突变分别为K103N/S 45.42%(104/229)、M184I/V 43.67%(100/229)和M46I 0.87%(2/229),其中与病毒载量5～ lg拷贝/mL相比,M184I/V耐药性突变在患者体内病毒载量3～拷贝/mL时更易出现(OR=0.283,95%CI为0.136～0.592,P＜0.001),与治疗时间6～个月相比,K103N/S耐药性突变在患者治疗时间48～个月时更易出现(OR=7.422,95%CI为1.637～33.651,P＜0.001),K65R突变位点在使用含D4T一线抗病毒治疗方案患者中发生率较高(P=0.044)。结论:河南省商丘市抗病毒治疗病毒未抑制人群中耐药性突变位点多、类型复杂,应根据耐药突变情况选用更适合的抗病毒起始治疗方案,以减少耐药毒株的产生。
Aim: To analyze the prevalence and diversity of genotype resistant mutations among patients failed to high antiretroviral therapy(HAART)in Henan Province.Methods: A total of 231 serum specimens of AIDS individuals with virus load ≥1 000 copies/mL were collected and had received more than six months treatment with HAART.The HIV-1 pol gene was amplified by RT-PCR,the sequences were then submitted to the Stanford University HIV drug resistance database to analyze the prevalence of resistant mutations.Results: A total of 229 plasma samples were amplified successfully for protease and reverse transcriptase fragments.Out of 229 sequences,185(80.79%),150(65.50%)and 3(1.31%)sequences occurred resistance mutations for non-nucleotide reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs)and protease inhibitors(PIs), respectively.The most common mutations to NNRTIs, NRTIs, and PIs were K103N/S 45.42%(104/229), M184I/V 43.67%(100/229)and M46I 0.87%(2/229), respectively. Univariate logistic regression analysis showed that among AIDS individuals, virus load 5- lg copies/mL decreased the risk of M184I/V mutation(OR=0.283,95%CI=0.136-0.592,P＜0.001)compared with virus load 3- lg copies/mL. More than 48 months treatment with HAART had high rate of K103N/S mutation(OR=7.422,95%CI=1.637-33.651,P＜0.001), compared with 6- months treatment. HAART with D4T was associated with high K65R mutation rate(P=0.044).Conclusion: The prevalence of HIV-1 drug resistance with complex patterns is higher among patients failed to HAART in Henan. Selecting more suitable antiretroviral treatment regimen is necessary to reduce the emergence of the drug resistant strains