ABSTRACT: Objective: To determine the genotypic reverse transcriptase (RT) profile of patients treated for over 6 months with a stavudine-containing regimen, naïve to zidovudine and with virological failure (>200 copies/ml).
Methods: The therapeutic history of 70 patients was carefully investigated to exclude any subject with zidovudine exposure. The RT profile of the patients was determined at the moment of virological failure and at baseline. Sequencing reactions were performed directly by RT nested RCR amplification using ABI Big Dye Terminator cycle sequencing and analyzed on an automatic ABI sequencer. RNA load was determined using an Amplicor HIV-1 Monitor test (Roche).
Results: In this study, 70 patients were genotypically assessed. At the time of virological failure 42 of the patients were following a stavudine-containing bitherapy regimen and 28 were following a stavudine containing tritherapy regimen, with or without protease inhibitors. Three kinds of genetic profile were observed (i) 4/70 (6%) harboring zidovudine-associated mutations at baseline (215E, 215D, 41L plus 210W plus 215Y/s, 67N plus 215S plus 219Q); (ii) 3/70 (4%) were wild-type at baseline and developed zidovudine-associated mutations at the time of failure (41L plus 210W plus 215F, 41L plus 215Y, 215Y); and (iii) 1/70 (1%) was wild-type at baseline and developed multidrug resistance mutations (F116Y, Q151M) at the time of failure. It is noteworthy that none of the patients harbored a mutation at codon 75.
Conclusion: Zidovudine resistance-associated mutations are observed in patients with failure to a stavudine-containing regimen. The duration of stavudine exposure seems to be an important parameter because patients who developed zidovudine-associated mutations had followed stavudine-containing regimens for 2.5 to 3 years. Phenotypic studies are on going.
