title: Genotypic and phenotypic resistance patterns at virological failure in a simplification trial with nevirapine, efavirenz or abacavir.
abstract: BACKGROUND
  The NEFA Study was a randomized study comparing nevirapine (NVP), efavirenz (EFV) or abacavir (ABC) as substitutes for protease inhibitors in a large group of HIV-1-infected patients successfully treated with antiretroviral regimens containing protease inhibitors.
  
  
  OBJECTIVE
  To evaluate genotype and phenotype resistance patterns among patients who have experienced virological failure under one of the three study arms.
  
  
  METHODS
  Patients with virological failure, defined as two consecutive determinations of HIV-1 RNA > 200 copies/ml, were analysed for phenotypic susceptibility and HIV-1 mutations.
  
  
  RESULTS
  Of the 460 patients included in the study, 51 (11%) experienced virological failure after 24 months of follow-up while on assigned study medication. A higher proportion of patients in the ABC [25 (17%)] than in the NVP [14 (9%)] or EFV [12 (8%)] arms selected resistance to the study drug (P = 0.04). Moreover, a much higher number of resistance mutations to one or more of the backbone nucleoside reverse transcriptase inhibitor drugs contained in the failing regimen were observed in the ABC than in the EFV or NVP arms. In general, there was a good concordance among genotype and phenotype resistance testing, except for ABC, stavudine and didanosine, where phenotypic resistance testing added valuable information (fold change in the median inhibitory concentration).
  
  
  CONCLUSIONS
  Cross-resistance involving nucleoside reverse transcriptase inhibitor drugs might explain the higher risk of virological failure in patients switched to ABC-containing antiretroviral therapy. Phenotypic resistance testing may be helpful in interpreting unclear genotypic results.
authors.affiliation: Hospital Mutua de Terrassa, Terrassa, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Ochoa de Echagüen
authors.forename: Mireia
authors.initials: M
authors.lastname: Arnedo
authors.forename: Mariona
authors.initials: M
authors.lastname: Xercavins
authors.forename: Esteban
authors.initials: E
authors.lastname: Martinez
authors.forename: Beatriz
authors.initials: B
authors.lastname: Rosón
authors.forename: Esteve
authors.initials: E
authors.lastname: Ribera
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.forename: Alicia
authors.initials: A
authors.lastname: González
authors.forename: Melcior
authors.initials: M
authors.lastname: Riera
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Llibre
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Gatell
authors.forename: David
authors.initials: D
authors.lastname: Dalmau
mesh_terms: D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D019829:Nevirapine / Q000494:pharmacology / Q000627:therapeutic use; D010078:Oxazines / Q000494:pharmacology / Q000627:therapeutic use; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure; D000099227:Abacavir
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D019829:Nevirapine; D010078:Oxazines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C098320:efavirenz