title: Human immunodeficiency virus type 1 (HIV-1) genotyping in Rio de Janeiro, Brazil: assessing subtype and drug-resistance associated mutations in HIV-1 infected individuals failing highly active antiretroviral therapy.
abstract: In order to assess the human immunodeficiency virus type 1 (HIV-1) drug resistance mutation profiles and evaluate the distribution of the genetic subtypes in the state of Rio de Janeiro, Brazil, blood samples from 547 HIV-1 infected patients failing antiretroviral (ARV) therapy, were collected during the years 2002 and 2003 to perform the viral resistance genotyping at the Renageno Laboratory from Rio de Janeiro (Oswaldo Cruz Foundation). Viral resistance genotyping was performed using ViroSeq Genotyping System (Celera Diagnostic-Abbott, US). The HIV-1 subtyping based on polymerase (pol) gene sequences (protease and reverse transcriptase-RT regions) was as follows: subtype B (91.2%), subtype F (4.9%), and B/F viral recombinant forms (3.3%). The subtype C was identified in two patients (0.4%) and the recombinant CRF_02/AG virus was found infecting one patient (0.2%). The HIV-1 genotyping profile associated to the reverse transcriptase inhibitors has shown a high frequency of the M184V mutation followed by the timidine-associated mutations. The K103N mutation was the most prevalent to the non-nucleoside RT inhibitor and the resistance associated to protease inhibitor showed the minor mutations L63P, L10F/R, and A71V as the more prevalent. A large proportion of subtype B was observed in HIV-1 treated patients from Rio de Janeiro. In addition, we have identified the circulation of drug-resistant HIV-1 subtype C and are presenting the first report of the occurrence of an African recombinant CRF_02/AG virus in Rio de Janeiro, Brazil. A clear association between HIV-1 subtypes and protease resistance mutations was observed in this study. The maintenance of resistance genotyping programs for HIV-1 failing patients is important to the management of ARV therapies and to attempt and monitor the HIV-1 subtype prevalence in Brazil.
authors.affiliation: Laboratório de AIDS e Imunologia Molecular, Departamento de Imunologia, Instituto Oswaldo Cruz-Fiocruz, 21045-900 Rio de Janeiro, RJ, Brazil. coutofer@ioc.fiocruz.br
authors.forename: J C
authors.initials: JC
authors.lastname: Couto-Fernandez
authors.forename: C
authors.initials: C
authors.lastname: Silva-de-Jesus
authors.forename: V G
authors.initials: VG
authors.lastname: Veloso
authors.forename: M
authors.initials: M
authors.lastname: Rachid
authors.forename: R S G
authors.initials: RS
authors.lastname: Gracie
authors.forename: S L
authors.initials: SL
authors.lastname: Chequer-Fernandez
authors.forename: S M
authors.initials: SM
authors.lastname: Oliveira
authors.forename: D
authors.initials: D
authors.lastname: Arakaki-Sanchez
authors.forename: P J N
authors.initials: PJ
authors.lastname: Chequer
authors.forename: M G
authors.initials: MG
authors.lastname: Morgado
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001938:Brazil; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics*; D016679:Genome, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D012367:RNA, Viral / Q000235:genetics; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease