title: Primary HIV-1 drug resistance in the C-terminal domains of viral reverse transcriptase among drug-naïve patients from Southern Brazil.
abstract: BACKGROUND
  Major and accessory drug resistance mutations have been recently characterized in the C-terminal RT subdomains of HIV-1, connection and RNase H. However, their presence in treatment-naïve patients infected with HIV-1 non-B subtypes remains largely unknown.
  
  
  OBJECTIVE
  To characterize the patterns of primary resistance at the C-terminal RT subdomains of HIV-1 infecting subjects in the southern region of Brazil, where HIV-1 subtypes B and C co-circulate.
  
  
  METHODS
  Plasma viral RNA was extracted from patients recently diagnosed for HIV infection (2005-2008). The protease and reverse transcriptase regions were PCR-amplified and sequenced. Infecting HIV subtypes were assigned by phylogenetic inference and drug resistance mutations were determined following the IAS consensus and recent reports on C-terminal RT mutations.
  
  
  RESULTS
  The major mutation to NNRTI T369I/V was found in 1.8% of patients, while A376S was present in another 8.3%. In the RNase H domain, the compensatory mutation D488E was more frequently observed in subtype C than in subtype B (p=0.038), while the inverse was observed for mutation Q547K (p<0.001). The calculated codon genetic barrier showed that 22% of subtype B isolates, but no subtype C, carried T360, requiring two transitions to change into the resistance mutation 360V.
  
  
  CONCLUSIONS
  Major resistance-conferring mutations to NNRTI were detected in 10% of RT connection domain viral sequences from treatment-naïve subjects. We showed for the first time that the presence of specific polymorphisms can constrain the acquisition of definite resistance mutations in the connection and RNase H subdomains of HIV-1 RT.
authors.affiliation: Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: André F
authors.initials: AF
authors.lastname: Santos
authors.forename: Jussara
authors.initials: J
authors.lastname: Silveira
authors.forename: Cláudia P
authors.initials: CP
authors.lastname: Muniz
authors.forename: Michele
authors.initials: M
authors.lastname: Tornatore
authors.forename: Lívia R
authors.initials: LR
authors.lastname: Góes
authors.forename: Raul A
authors.initials: RA
authors.lastname: Mendoza-Sassi
authors.forename: Ana M B
authors.initials: AM
authors.lastname: Martinez
authors.forename: Unaí
authors.initials: U
authors.lastname: Tupinambás
authors.forename: Dirceu B
authors.initials: DB
authors.lastname: Greco
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Soares
mesh_terms: D000328:Adult; D001938:Brazil / Q000453:epidemiology; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology* / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D017422:Sequence Analysis, DNA
chemical_list: D012367:RNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase