title: Analysis of drug resistance-associated mutations in treatment-naïve individuals infected with different genetic forms of HIV-1 circulating in countries of the former Soviet Union.
abstract: There are few data on drug resistance-associated mutations in the former Soviet Union since, studies have usually been focused on the env or gag genes for subtype information. This study examines the prevalence and patterns of resistance-associated mutations to reverse transcriptase and protease inhibitors (RTI, PRI) in 278 HIV-1-infected treatment-naïve subjects from countries of Eastern Europe, and defines characteristic polymorphisms of RT and PR sequences in HIV-1 subtype A viruses. Blood samples were collected between 1997 and 2004. Plasma RNA was used for PR-RT amplification by reverse transcription coupled with nested PCR and sequencing. Phylogenetic analysis was done with neighbor-joining trees and bootscanning. Analysis of drug resistance mutations, with Stanford University HIV Drug Resistance Database's algorithm, resulted in an overall prevalence of 12.9% resistance to RTI and 3.9% to PRI. The most frequent substitutions in the RT region were at positions 62 and 236. V77I substitution in PR was found in 47.8% of samples. Polymorphisms in subtype A sequences were identified. This is the first study reporting the prevalence and patterns of both PRI and RTI resistance-associated mutations in naïve HIV-1 infected patients from the former Soviet Union. These data underline the importance of genotypic resistance testing of chronically HIV-1-infected patients before initiating treatment, in order to select the most suitable drug regimen.
authors.affiliation: Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Vázquez de Parga
authors.forename: A
authors.initials: A
authors.lastname: Rakhmanova
authors.forename: L
authors.initials: L
authors.lastname: Pérez-Alvarez
authors.forename: A
authors.initials: A
authors.lastname: Vinogradova
authors.forename: E
authors.initials: E
authors.lastname: Delgado
authors.forename: M M
authors.initials: MM
authors.lastname: Thomson
authors.forename: G
authors.initials: G
authors.lastname: Casado
authors.forename: M
authors.initials: M
authors.lastname: Sierra
authors.forename: M
authors.initials: M
authors.lastname: Muñoz
authors.forename: R
authors.initials: R
authors.lastname: Carmona
authors.forename: Y
authors.initials: Y
authors.lastname: Vega
authors.forename: G
authors.initials: G
authors.lastname: Contreras
authors.forename: L
authors.initials: L
authors.lastname: Medrano
authors.forename: S
authors.initials: S
authors.lastname: Osmanov
authors.forename: R
authors.initials: R
authors.lastname: Nájera
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011110:Polymorphism, Genetic; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood; D011995:Recombination, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D014586:USSR / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease