title: Drug resistance in patients experiencing early virological failure under a triple combination including indinavir.
abstract: OBJECTIVE
  To assess the pattern of drug resistance mutations selected in HIV-1-infected patients failing a first line triple combination therapy including indinavir.
  
  
  METHODS
  Plasma samples from 87 patients collected at the time of the first virological rebound (> 50 HIV-RNA copies/ml) were examined for the presence of drug-resistant genotypes.
  
  
  RESULTS
  The mean level of plasma viraemia at rebound was 7824 HIV-1 RNA copies/ml in 73 subjects with good compliance, whereas it was 359,460 HIV-1 RNA copies/ml in 14 patients who admitted to poor adherence. Genetic sequence analysis yielded results for 51 (70%) of the patients having good adherence. More than half of them (26/51, 51%) carried primary mutations associated with resistance to nucleoside analogues. In contrast, primary protease inhibitor resistance mutations were recognized less frequently (14/51, 27%; P < 0.05). Moreover, in 23 (45%) patients there was no evidence of drug-resistant viruses at all. The most frequent drug-resistant genotypes in the reverse transcriptase gene were at codons 184 (n = 19), 215 (n = 14) and 41 (n = 8), whereas for the protease they were at codons 46 (n = 10), 82 (n = 9) and 90 (n = 7). No resistance genotypes were found among non-compliant patients.
  
  
  CONCLUSIONS
  The overall rate of drug-resistant HIV genotypes was 38% (28/73) in patients with good adherence and who were experiencing a first virological failure under a triple combination regimen including indinavir; resistance to nucleoside analogues was more frequent than resistance to indinavir. Therefore, treatment intensification in those patients without resistance, or a selective substitution of nucleosides in those with resistance limited to these compounds, might be justified.
authors.affiliation: Service of Infectious Diseases, Instituto de Salud Carlos III, Barcelona, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Gallego
authors.forename: C
authors.initials: C
authors.lastname: de Mendoza
authors.forename: M J
authors.initials: MJ
authors.lastname: Pérez-Elías
authors.forename: J M
authors.initials: JM
authors.lastname: Guardiola
authors.forename: J
authors.initials: J
authors.lastname: Pedreira
authors.forename: D
authors.initials: D
authors.lastname: Dalmau
authors.forename: J
authors.initials: J
authors.lastname: Gónzalez
authors.forename: A
authors.initials: A
authors.lastname: Moreno
authors.forename: J R
authors.initials: JR
authors.lastname: Arribas
authors.forename: A
authors.initials: A
authors.lastname: Rubio
authors.forename: I
authors.initials: I
authors.lastname: García-Arata
authors.forename: M
authors.initials: M
authors.lastname: Leal
authors.forename: P
authors.initials: P
authors.lastname: Domingo
authors.forename: V
authors.initials: V
authors.lastname: Soriano
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019469:Indinavir / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir; D054303:HIV Reverse Transcriptase; D016333:HIV Protease