title: Long-term outcome of HIV-infected patients with multinucleoside-resistant genotypes.
abstract: BACKGROUND
  Multiple resistance to nucleoside analogs mediated by the Q151M complex and/or codon 67-69 inserts/deletions represents a growing problem among HIV-infected persons, most of whom have been exposed to sequential therapies for long periods of time.
  
  
  METHODS
  All plasma samples collected from HIV-infected patients failing antiretroviral therapy and referred for HIV genotyping to our institution during the last 3 years were examined. Genetic analysis of the reverse transcriptase (RT) and protease (PR) genes was performed using an automatic sequencer.
  
  
  RESULTS
  Multinucleoside-resistance (MNR) genotypes were recognized in 22 (2.9%) of 761 participants. Twelve of them carried the Q151M complex and 9 harbored different codon 67-69 inserts. One participant carried a deletion at codon 67 of the RT gene. All patients with MNR viruses had been exposed to nucleoside analogs for a median of 54 months (range, 19-96). The mean plasma HIV RNA at the time MNR was first identified was 4.62 log and the mean CD4 count was 227 cells/microL. All patients with MNR viruses except two began salvage therapies based on protease inhibitors (PIs). Overall, 54.5% (12/22) of participants showed a significant virologic response (defined as >1 log reduction in plasma HIV RNA). Seven of them reached <50 copies/mL and remained with undetectable viremia for a median of 17 months (range, 8-50). No differences were found when patients with Q151M and codon 67-69 rearrangements were compared. The only predictor of response was the inclusion of ritonavir-boosted PI in the salvage regimen. In all patients with virologic failure, MNR genotypes have persisted over time.
  
  
  CONCLUSIONS
  The prevalence of viruses with MNR genotypes is currently low (approximately 3%) among HIV-infected patients failing antiretroviral therapy. The expected poor prognosis of patients harboring MNR viruses may often be overcome using rescue interventions based on potent ritonavir-boosted PI combinations.
authors: Service of Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain.
authors: Oscar
authors: O
authors: Gallego
authors: Carmen
authors: C
authors: d Mendoza
authors: Pablo
authors: P
authors: Labarga
authors: Carmen
authors: C
authors: Altisent
authors: Juan
authors: J
authors: González
authors: Isabel
authors: I
authors: García-Alcalde
authors: Luisa
authors: L
authors: Valer
authors: Eulalia
authors: E
authors: Valencia
authors: Vincent
authors: V
authors: Soriano
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016879:Salvage Therapy; D017741:Survivors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral