title: Emergence of drug resistance-associated mutations in HIV-1 subtype C protease gene in north India.
abstract: A major cause of anti-retroviral therapy (ART) failure is the drug resistance-associated mutations in polymerase gene of HIV-1. Paucity of data regarding potential drug resistance to protease inhibitors (PIs) prompted us to carry out this study. Drug resistance (DR) genotyping of the entire protease gene was performed in 104 HIV-1 ART-naive and first-line ART-experienced patients. The DR pattern was analyzed using the Stanford HIV-DR database, International AIDS Society-USA mutation list and REGA algorithm version 8.0. Subtyping was done using Mega 4 and REGA HIV-1 subtyping tool-v2.01. Majority of our sequences 98 (96%) were subtype C and remaining four (3.92%) were subtype A1. In three (2.9%) DE patients, major DR-associated mutation at D30 N and M46I positions were detected. Approximately 70% polymorphisms as minor mutations were observed in protease gene, of which 14 distinct amino acids changes were linked to partial DR such as G16E, K20R, M36I, D60E, I62V, L63P, I64M, H69K, T74A/S, V77I, V82I, I85V, L89M, and I93L. The two major and several minor mutations detected in this study confer low/intermediate levels of resistance to most PIs independently or together. Our results conclude that resistance testing in HIV-1-infected patients should be performed before the initiation of PI therapy for better therapeutic outcome in this region. This information not only will shed light on the extent of current DR in HIV strains but also will aid in patient treatment and drug designing.
authors.affiliation: Department of Microbiology, Faculty of Medicine, J.N. Medical College, Aligarh Muslim University, Aligarh, 202002, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Azam
authors.forename: Abida
authors.initials: A
authors.lastname: Malik
authors.forename: Meher
authors.initials: M
authors.lastname: Rizvi
authors.forename: Supriya
authors.initials: S
authors.lastname: Singh
authors.forename: Poonam
authors.initials: P
authors.lastname: Gupta
authors.forename: Arvind
authors.initials: A
authors.lastname: Rai
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; D012697:Serine Endopeptidases; C088701:protease C