title: Failure of stavudine-lamivudine combination therapy in antiretroviral-naive patients with AZT-like HIV-1 resistance mutations.
abstract: To analyze the clinical relevance of AZT resistance mutations in AZT-naive patients, 56 HIV-1 seropositive patients treated for 18 months with stavudine/lamivudine (27 patients) or AZT/lamivudine (29 patients) were studied. AZT-like resistance mutations were found in 13 out of 29 (44%) patients treated with AZT/lamivudine and in 11 out of 27 (40%) patients treated with stavudine/lamivudine. No stavudine or multi-drug resistance mutations were detected. After 26 months of treatment more than 60% of patients showed a virological failure. Among 10 patients failing treatment with stavudine/lamivudine, 9 had AZT-like resistance mutations. The phenotypic test, performed on HIV-1 strains isolated from six of these nine patients, showed a resistance to AZT in five isolates and to stavudine in two isolates. The genotypic pattern of the latter two isolates showed the combined mutations M184V plus R211K and L214F. AZT-like resistance mutations in AZT-naive patients seem to correlate with a virological failure during long-term stavudine therapy.
authors.affiliation: Department of Public Health, University of Rome Tor Vergata, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Sarmati
authors.forename: E
authors.initials: E
authors.lastname: Nicastri
authors.forename: S G
authors.initials: SG
authors.lastname: Parisi
authors.forename: G
authors.initials: G
authors.lastname: D'Ettorre
authors.forename: P
authors.initials: P
authors.lastname: Narciso
authors.forename: G
authors.initials: G
authors.lastname: Mancino
authors.forename: I
authors.initials: I
authors.lastname: Gallo
authors.forename: V
authors.initials: V
authors.lastname: Abbadessa
authors.forename: N E
authors.initials: NE
authors.lastname: Dalle
authors.forename: C
authors.initials: C
authors.lastname: Traina
authors.forename: V
authors.initials: V
authors.lastname: Vullo
authors.forename: M
authors.initials: M
authors.lastname: Andreoni
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D006679:HIV Seropositivity / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D009154:Mutation; D018119:Stavudine / Q000627:therapeutic use*; D017211:Treatment Failure; D015215:Zidovudine / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine; D015215:Zidovudine; D018119:Stavudine