2008-2013年福建省HIV-1毒株耐药基因变异研究

Evaluation on drug-resistant gene mutation of HIV-1 strains in Fujian Province,China,2008-2013

目的分析2008-2013年福建HIV-1毒株耐药基因变异情况。方法收集2008-2013年福建省病毒载量大于1 000copy/mL艾滋病患者,采用自建HIV-1基因型耐药检测进行耐药检测和分析。结果共收集226例病毒载量大于1 000copy/mL样本,平均载量值1.62×105copy/mL;124例样本扩增及测序后获得蛋白酶以及部分反转录酶基因序列,亚型分析显示92例(74.2%)为CRF_01AE亚型,14例(11.3%)为B亚型,C和BC亚型各有7例,另4例为其他亚型。77对反转录酶以及蛋白酶抑制剂有不同程度耐药;对核苷类和非核苷类反转录酶抑制剂的耐药分别有63例(50.8%)和74例(59.7%),对蛋白酶抑制剂耐药9例(7.3%);核苷类反转录酶抑制剂主要耐药突变包括了M184V、M41L、D67N、L70R、T219F、K219Q等,造成对3TC、AZT、D4T等不同程度耐药;非核苷类反转录酶抑制主要耐药突变包括K101E、Y181C、K103N、G190A等,造成对NVP和EFV不同程度耐药。结论福建省HIV-1感染者总体耐药率较低,但是随着治疗人数增加以及治疗时间延长,对反转录酶抑制剂出现较高程度耐药,仍需加强艾滋病患者耐药检测。

To evaluate the drug-resistance gene mutation of HIV-1 strains in Fuiian Province, 226 samples with viral load of HIV-1 in plasma above 1 000 copy/mL were collected from 2008 to 2013. The average of viral load was 1.62 × 10^5 copy/mL. Then the whole sequence of gene including the pol gene and the partial reverse transcriptase gene of HIV-1 were amplified by RT-PCR, in which 124 samples were amplified successfully and then the sequences of those amplified ones were edited by the software Conting Express and submitted to the website http//hivdb, stanford, edu./to analyze the drug resistance status. It was found that 92 samples （74.2%） of that strains were classified as CRF_01AE, 14 samples were B, C and BC were 7 samples, respectively. According to the interpretation of Stanford University drug resistance database, 63 of 124 sequences occurred mu- tations for NRTIs, 74 of 124 sequences occurred mutations for NNRTIs, and 9 of 124 sequences occurred mutations for PIs. The NRTI resistance mutations were M184V, M41L, D67N, L70R, T219F, and K219Q, which caused high or medium level of resistance to TDF, 3TC, D4T and so on. The NNRTI resistance mutations were K101E, Y181C, K103N, and G190A, which caused high or medium level of EFV and NVP. These results showed that the rate of total drug resistance mutation of HIV-1 in Fujian Province was low. But with the increase of the populations using highly active anti-retrovirus therapy and the length of the time during therapy, the mutation may cause high or medium level of drug resistance, so the surveillance for that of HIV-1 is necessary.