Azam Mohd, Malik Abida, Rizvi Meher, Rai Arvind
J.N.M.C., Faculty of Medicine, Aligarh Muslim University, Aligarh, India.
J Infect Dev Ctries. 2014 Jan 15;8(1):79-85. doi: 10.3855/jidc.3480.
This study aimed to evaluate the prevalence of resistance mutations in the protease gene of HIV-1 strains isolated from north Indian antiretroviral (ARV) treatment-naive patients and to assess the phylogenetic relatedness of these strains with known HIV-1 strains.
Fifty-four HIV-1 strains isolated from treatment-naive patients (n = 54) were included in this study. Resistance genotyping for the protease gene was performed using semi-nested PCR and DNA sequencing. The sequences were aligned (ClustalW) and a phylogenetic tree was built (MEGA 4 software). Drug resistance (DR) pattern was analyzed using the Stanford HIV-DR database and the IAS-USA mutation list. For subtyping purposes, all the nucleotide sequences were submitted to the REGA HIV-1 subtyping tool version 2.0l.
All the strains (100%) were found to belong to the C subtype and to harbor at least two secondary mutations in the protease gene. The most frequent mutations were H69K and I93L (52 of 52 strains), followed by I15V (80.7%), L19I (69.2%), M36I (67.3%), R41K (94.2%), L63P (61.5%), and L89M (82.7%).
This study confirms that HIV-1 subtype C predominates in northern India. Protease secondary mutations associated with drug resistance to protease inhibitors (PIs) were present with high frequency in the HIV-1 C subtype strains isolated from north Indian ARV treatment-naive patients, but no primary resistance mutations were found in this region. We suggest that resistance testing in HIV-1 infected patients should ideally be performed before the initiation of therapy to tailor the treatment for the individual to achieve the optimal therapeutic outcome.
本研究旨在评估从印度北部未接受过抗逆转录病毒(ARV)治疗的患者中分离出的HIV-1毒株蛋白酶基因中耐药突变的流行情况,并评估这些毒株与已知HIV-1毒株的系统发育相关性。
本研究纳入了54株从未接受过治疗的患者中分离出的HIV-1毒株(n = 54)。使用半巢式PCR和DNA测序对蛋白酶基因进行耐药基因分型。对序列进行比对(ClustalW)并构建系统发育树(MEGA 4软件)。使用斯坦福HIV耐药数据库和IAS-USA突变列表分析耐药模式。为了进行亚型分析,所有核苷酸序列都提交给了REGA HIV-1亚型分析工具2.0l版。
所有毒株(100%)均属于C亚型,且在蛋白酶基因中至少含有两个二级突变。最常见的突变是H69K和I93L(52株中的52株),其次是I15V(80.7%)、L19I(69.2%)、M36I(67.3%)、R41K(94.2%)、L63P(61.5%)和L89M(82.7%)。
本研究证实HIV-1 C亚型在印度北部占主导地位。从印度北部未接受过ARV治疗的患者中分离出的HIV-1 C亚型毒株中,与蛋白酶抑制剂(PIs)耐药相关的蛋白酶二级突变高频出现,但在该地区未发现原发性耐药突变。我们建议,对于HIV-1感染患者,理想情况下应在开始治疗前进行耐药检测,以便为个体量身定制治疗方案,从而实现最佳治疗效果。