Prevalence of G333D/E in naive and pretreated HIV-infected patients

A substitution at codon 333 (G -->D/E) within the reverse transcriptase (RT) gene causes resistance to both zidovudine (AZT) and lamivudine (3TC) in a background of mutations associated with loss of sensitivity to both drugs. In the absence of G333D/E, M184V restores the sensitivity to AZT in viruses harboring AZT-resistant genotypes. In this study, we examined the prevalence of the G333D/E mutation in plasma samples from 401 HIV-infected individuals from a routine clinical practice. Genotypic results could be obtained in 277 (81%) specimens belonging to pretreated subjects and in all 65 samples from treatment-naive individuals. The overall prevalence of the G333D/E mutation was 13.2%, without significant differences when comparing naive (10.8%) and treatment-experienced patients (13.7%). The codon 333 mutation was associated with AZT/3TC-resistant genotypes in 76.3% of pretreated individuals but in none of the treatment-naive individuals. In conclusion, the G333D/E mutation must be considered a natural polymorphism, which appears in 11% of treatment-naive HIV-infected individuals. In AZT-experienced patients, it might be advisable to exclude its presence before adding 3TC in combination in the hope of obtaining a restoration of AZT sensitivity if M184V develops.