在来自印度的C型HIV-1感染个体中,对治疗失败患者进行基因分型耐药性检测所发现的耐药突变。
Drug resistant mutations detected by genotypic drug resistance testing in patients failing therapy in clade C HIV-1 infected individuals from India.
作者信息
Kandathil A J, Kannangai R, Verghese V P, Pulimood S A, Rupali P, Sridharan G, Grant P, Pillay D, Abraham O C
机构信息
Department of Clinical Virology, Christian Medical College, Vellore, India.
出版信息
Indian J Med Microbiol. 2009 Jul-Sep;27(3):231-6. doi: 10.4103/0255-0857.53205.
PURPOSE
There has been an increase in the number of individuals administered antiretroviral therapy (ART) in India but treatment outcome is hampered by increasing development of drug resistance. Previous reports from India have shown M184V as the commonest mutation in treated individuals. However, there is no evidence for any protease mutations in these reports. This study was done to observe the common/unique mutational patterns observed in reverse transcriptase (RT) and protease (Pr) genes of clade C HIV-1 strains from individuals showing treatment failure in India.
MATERIALS AND METHODS
The assay was done by sequencing the Pr and RT genes of the HIV-1 strains from 18 individuals failing ART. Analysis was carried out using Stanford HIV drug resistance database (SHDB). The sequences were also submitted to the calibrated population resistance tool of SHDB and Rega HIV-1 sub typing tool. Phylogenetic analysis and quality control were performed with Mega 4.
RESULTS
Among the 20 strains, 19 showed resistance to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), one strain to NNRTIs and five strains showed protease inhibitors (PI) resistance and 3-class resistance. The most common mutation conferring NRTI resistance was M184V (90%) while K103N (45%) was the most common mutation conferring NNRTI resistance. The M46I mutation was seen in 20% of the Pr sequences.
CONCLUSION
Resistance testing to check the prevalence of drug resistance mutations that arise following failure of the first line regimen to establish guidelines for second line regimens in India is a must. Studies are needed to confirm if mutation patterns that arise among clade C following failure of ART are the same as for clade B strains.
目的
印度接受抗逆转录病毒疗法(ART)的人数有所增加,但耐药性的不断发展阻碍了治疗效果。印度此前的报告显示,M184V是接受治疗者中最常见的突变。然而,这些报告中没有任何蛋白酶突变的证据。本研究旨在观察印度治疗失败个体的C型HIV-1毒株逆转录酶(RT)和蛋白酶(Pr)基因中常见/独特的突变模式。
材料与方法
通过对18例ART治疗失败个体的HIV-1毒株的Pr和RT基因进行测序来进行检测。使用斯坦福HIV耐药数据库(SHDB)进行分析。序列还提交给了SHDB的校准群体耐药性工具和雷加HIV-1亚型分型工具。使用Mega 4进行系统发育分析和质量控制。
结果
在20株毒株中,19株对核苷类逆转录酶抑制剂(NRTIs)和非核苷类逆转录酶抑制剂(NNRTIs)均耐药,1株对NNRTIs耐药,5株对蛋白酶抑制剂(PIs)耐药且具有3类耐药性。导致NRTI耐药的最常见突变是M184V(90%),而导致NNRTI耐药的最常见突变是K103N(45%)。在20%的Pr序列中发现了M46I突变。
结论
在印度,进行耐药性检测以检查一线治疗方案失败后出现的耐药性突变的流行情况,对于制定二线治疗方案的指南是必不可少的。需要开展研究以确认ART治疗失败后C型毒株中出现的突变模式是否与B型毒株相同。