摘要
目的 研究我国东北地区未接受抗逆转录病毒治疗的HIV AIDS患者HIV毒株的逆转录酶和蛋白酶耐药变异情况 ,为开展大规模临床抗病毒药物治疗提供本底数据。方法 RT PCR和套式PCR扩增HIVpol区基因 ,双脱氧法测定逆转录酶和蛋白酶基因序列 ,与国际耐药数据库比对辨别耐药变异。结果 (1) 5 3例患者毒株亚型分析结果 :B′亚型 4 7例 ,B′ C亚型 4例 ,A、B亚型各 1例 ;(2 )未发现逆转录酶和蛋白酶原发耐药变异存在 ,但发现存在逆转录酶抑制剂继发变异 :M4 1L(1.9% )、I6 3M (1.9% )、L74I (1.9% )、S6 8G (1.9% )、V75L (3.8% )、V10 6I (1.9% )、I135L T (5 .7% )、V179D (7.5 % )和V189I (1.9% ) ,无症状感染者RT继发耐药变异出现率为 11.8% ,而艾滋病患者为5 2 .6 % (P <0 .0 1)。存在大量蛋白酶耐药继发变异V77I (88.7% )、L6 3P (86 .8% )、E35D (81% )、A71V(2 4 .5 % )、R4 1K (15 .1% )、L10I (9.4 % )、R5 7K (9.4 % )、D6 0E (9.4 % )、N37D (5 .7% )、G16E (3.8% )、I15V (1.9% )、M36I (1.9% )、K5 5R (1.9% )和L89M (1.9% )。未发现明显的亚型特异性耐药变异。结论 在中国东北地区未接受抗逆转录病毒治疗的HIV AIDS患者中未发现毒株逆转录酶和蛋白酶耐药原发变异 。
Objective To study the drug resistance mutations of reverse transcriptase (RT) and protease among HIV-1 strains of treatment-naive HIV/AIDS patients in the northeast of China, provide the base-line data for clinical antiviral treatment in China. Methods We amplified partial pol sequences by RT-PCR and nest-PCR, then sequenced the gene segment. The results compared to the subtype B consensus amino acid sequence Stanford HIV protease sequence database. Results Phylogenetic analysis revealed that 47 of the sequences were classified as subtype B′, 1 as subtype A, 1 as subtype B, and 4 as B′/C recombinant strains according to pol region sequence. No primary mutation associated with protease and RT was detected. Some secondary mutations associated with RT inhibitor were detected: M41L(1.9%), I63M (1.9%), L74I (1.9%), S68G (1.9%), V75L ((3.8%)), V106I (1.9%), I135L/T (5.7%), V179D (7.5%) and V189I (1.9%). In asymptomatic HIV-1 infected individuals, the mean RT related drug resistance mutations were 11.8% strains, while in AIDS patients, the mean RT related drug resistance mutations were 52.6% strains (P<0.01). There are many secondary mutations to protease inhibitor (PI): V77I (88.7%), L63P (86.8%), E35D (81%), A71V (24.5%), R41K (15.1%), L10I (9.4%), R57K (9.4%), D60E (9.4%), N37D (5.7%), G16E (3.8%), I15V ((1.9%)), M36I (1.9%), K55R (1.9%) and L89M (1.9%). No mutations specific for a given subtype were noted. Conclusion No major mutations associated with RT and protease of HIV-1 were seen. This study reveals that virus infecting these treatment naive Chinese patients have acquired many secondary mutations in their PR and RT genes, which reminded us to pay more attention to the drug resistance mutations observation and prevention of the prevalence of crossing drug resistance and multi-drug resistance. [
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
2004年第11期850-854,共5页
Chinese Journal of Microbiology and Immunology
基金
卫生部艾滋病防治研究项目 (No .WA2 0 0 3 0 1)
