title: Comparative analysis of drug resistance mutations in the human immunodeficiency virus reverse transcriptase gene in patients who are non-responsive, responsive and naive to antiretroviral therapy.
abstract: Drug resistance mutations in the Pol gene of human immunodeficiency virus 1 (HIV-1) are one of the critical factors associated with antiretroviral therapy (ART) failure in HIV-1 patients. The issue of resistance to reverse transcriptase inhibitors (RTIs) in HIV infection has not been adequately addressed in the Indian subcontinent. We compared HIV-1 reverse transcriptase (RT) gene sequences to identify mutations present in HIV-1 patients who were ART non-responders, ART responders and drug naive. Genotypic drug resistance testing was performed by sequencing a 655-bp region of the RT gene from 102 HIV-1 patients, consisting of 30 ART-non-responding, 35 ART-responding and 37 drug-naive patients. The Stanford HIV Resistance Database (HIVDBv 6.2), IAS-USA mutation list, ANRS_09/2012 algorithm, and Rega v8.02 algorithm were used to interpret the pattern of drug resistance. The majority of the sequences (96 %) belonged to subtype C, and a few of them (3.9 %) to subtype A1. The frequency of drug resistance mutations observed in ART-non-responding, ART-responding and drug-naive patients was 40.1 %, 10.7 % and 20.58 %, respectively. It was observed that in non-responders, multiple mutations were present in the same patient, while in responders, a single mutation was found. Some of the drug-naive patients had more than one mutation. Thymidine analogue mutations (TAMs), however, were found in non-responders and naive patients but not in responders. Although drug resistance mutations were widely distributed among ART non-responders, the presence of resistance mutations in the viruses of drug-naive patients poses a big concern in the absence of a genotyping resistance test.
authors.affiliation: Molecular Virology Laboratory, Department of Biotechnology, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Misbah
authors.affiliation: Molecular Virology Laboratory, Department of Biotechnology, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Roy
authors.affiliation: Molecular Virology Laboratory, Department of Biotechnology, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
authors.forename: Mudassar
authors.initials: M
authors.lastname: Shahid
authors.affiliation: Department of Internal Medicine, Indraprastha Apollo Hospitals, New Delhi, India.
authors.forename: Nalin
authors.initials: N
authors.lastname: Nag
authors.affiliation: Department of Medicine, Maulana Azad Medical College, New Delhi, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Molecular Virology Laboratory, Department of Biotechnology, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India. mhusain2@jmi.ac.in.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Husain
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase