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 stavudi ne/lamivudine (27 patients) or AZT/lamivudine (29 patients) were studied. A ZT-like resistance mutations were found in 13 out of 29 (44%) patients trea ted with AZT/lamivudine and in 11 out of 27 (40%) patients treated with sta vudine/lamivudine. No stavudine or multidrug resistance mutations were dete cted. After 26 months of treatment more than 60% of patients showed a virol ogical failure. Among 10 patients failing treatment with stavudine/lamivudi ne, 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 pa ttern of the latter two isolates showed the combined mutations M184V plus R 211K and L214F. AZT-like resistance mutations in AZT-naive patients seem to correlate with a virological failure during long-term stavudine therapy. ( C) 2001 Wiley-Liss, Inc.