Bure Dinesh, Makhdoomi Muzamil A, Lodha Rakesh, Prakash Somi Sankaran, Kumar Rajesh, Parray Hilal A, Singh Ravinder, Kabra Sushil K, Luthra Kalpana
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India.
Department of Pediatrics, New Delhi 110029, India.
Viruses. 2015 Feb 10;7(2):590-603. doi: 10.3390/v7020590.
The success of highly active antiretroviral therapy (HAART) is challenged by the emergence of resistance-associated mutations in human immunodeficiency virus-1 (HIV-1). In this study, resistance associated mutations in the reverse transcriptase (RT) and protease (PR) genes in antiretroviral therapy (ART) naïve and treated HIV-1 infected pediatric patients from North India were evaluated. Genotyping was successfully performed in 46 patients (30 ART naive and 16 treated) for the RT gene and in 53 patients (27 ART naive and 26 treated) for PR gene and mutations were identified using Stanford HIV Drug Resistance Database. A major drug resistant mutation in RT gene, L74I (NRTI), and two such mutations, K101E and G190A (NNRTI), were observed in two ART naïve patients, while M184V was detected in two ART treated patients. Overall, major resistance associated mutations in RT gene were observed in nine (30%) and seven (36%) of ART naïve and treated children respectively. Minor mutations were identified in PR gene in five children. Few non-clade C viral strains (≈30%) were detected, although subtype C was most predominant. The screening of ART naïve children for mutations in HIV-1 RT and protease genes, before and after initiation of ART is desirable for drug efficacy and good prognosis.
高效抗逆转录病毒疗法(HAART)的成功受到人类免疫缺陷病毒1型(HIV-1)中耐药相关突变出现的挑战。在本研究中,对印度北部初治和接受过抗逆转录病毒治疗(ART)的HIV-1感染儿科患者逆转录酶(RT)和蛋白酶(PR)基因中的耐药相关突变进行了评估。46例患者(30例初治患者和16例接受治疗患者)成功进行了RT基因分型,53例患者(27例初治患者和26例接受治疗患者)成功进行了PR基因分型,并使用斯坦福HIV耐药数据库鉴定了突变。在两名初治患者中观察到RT基因中的主要耐药突变L74I(核苷类逆转录酶抑制剂),以及两个此类突变K101E和G190A(非核苷类逆转录酶抑制剂),而在两名接受ART治疗的患者中检测到M184V。总体而言,初治和接受治疗的儿童中分别有9例(30%)和7例(36%)观察到RT基因中的主要耐药相关突变。在5名儿童的PR基因中鉴定出了次要突变。尽管C亚型最为常见,但检测到少量非C亚型病毒株(约30%)。对初治儿童在开始ART之前和之后进行HIV-1 RT和蛋白酶基因突变筛查,对于药物疗效和良好预后是可取的。