Failure of stavudine-lamivudine combination therapy in antiretroviral-naive patients with AZT-like HIV-1 resistance mutations.
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.
Sarmati
L
L
Department of Public Health, University of Rome Tor Vergata, Rome, Italy.
Nicastri
E
E
Parisi
S G
SG
D'Ettorre
G
G
Narciso
P
P
Mancino
G
G
Gallo
I
I
Abbadessa
V
V
Dalle
N E
NE
Traina
C
C
Vullo
V
V
Andreoni
M
M
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*
D019380:Anti-HIV Agents; D019259:Lamivudine; D015215:Zidovudine; D018119:Stavudine