论文部分内容阅读
目的分析河南省中部地区艾滋病一线抗病毒治疗失败患者HIV-1耐药基因突变情况。方法采集河南省一线抗病毒治疗>6个月,病毒载量≥1000拷贝/ml的309例艾滋病患者血样标本,提取病毒RNA,通过逆转录及巢式PCR扩增HIV-1pol区基因,测序后提交斯坦福大学HIV耐药数据库进行耐药基因突变分析。结果在扩增的309份pol基因区片段中,RT区主要耐药突变为K103N/S 44.34%(137/309),其余依次是M184I/V 43.69%(135/309)、T215F/Y 31.07%(96/309)、Y181C29.77%(92/309)、G190A/S 22.01%(68/309)和D67N19.42%(60/309)等。其中患者体内病毒载量为4~5lg拷贝/ml和>5lg拷贝/ml较3~4lg拷贝/ml时更不易出现M184I/V耐药突变(OR值分别为0.569和0.316,P<0.05),K103N/S、M184I/V、M41L和K219Q/E/R/N突变位点在治疗时间>48个月时发生相应耐药突变比例较治疗时间<24个月时升高(OR值分别为3.135、2.620、2.413和3.605,P<0.05)。有79.61%、64.72%和0.97%的患者感染的HIV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)产生耐药。结论艾滋病抗病毒治疗失败者HIV-1基因耐药性突变位点多,比例高,类型较复杂,因此应根据耐药突变情况选用适合的抗病毒治疗方案,以减少耐药毒株的产生。
Objective To analyze the mutations of HIV-1 resistance gene in patients with failed first-line ARV treatment in central Henan province. Methods A total of 309 AIDS patients were collected from first-line antiviral therapy in Henan Province for> 6 months and the viral load was ≥1000 copies / mL. The viral RNA was extracted and the HIV-1pol gene was amplified by reverse transcription and nested PCR. Submitted to Stanford University HIV drug resistance database for resistance gene mutation analysis. Results Among the 309 pol gene fragments amplified, the major resistance mutations in RT were K (44.34)% (137/309) and the rest followed by M184I / V 43.69% (135/309) and T215F / Y 31.07% (96/309), Y181C29.77% (92/309), G190A / S 22.01% (68/309) and D67N19.42% (60/309) and the like. Among them, M184I / V resistant mutations were less likely to occur in patients with viral load of 4 ~ 5lg copies / ml and> 5lg copies / ml compared with 3 ~ 4lg copies / ml (OR = 0.569 and 0.316 respectively, P <0.05) The proportion of corresponding drug-resistant mutations in K103N / S, M184I / V, M41L and K219Q / E / R / N mutation sites at treatment time> 48 months was higher than that at treatment time <24 months , 2.620, 2.413 and 3.605, P <0.05). HIV infection in 79.61%, 64.72%, and 0.97% of patients was resistant to NNRTIs, NRTIs and PIs. Conclusion There are many sites of HIV-1 gene mutation in HIV-1 patients with failed HIV / AIDS treatment. The types of HIV-1 gene mutation are high and the types are complex. Therefore, appropriate anti-virus treatment should be selected based on the mutation of HIV-1 so as to reduce the generation of drug-resistant strains.