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.
Service of Infectious Diseases, Hospital Carlos III, Instituto de Salud Carlos III, Madrid 28029, Spain.
Oscar
O
Gallego
Angélica
A
Corral
Carmen
C
de Mendoza
Berta
B
Rodés
Vincent
V
Soriano
D000595:Amino Acid Sequence; D004352:Drug Resistance, Microbial / Q000235:genetics; D015658:HIV Infections / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology
D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D054303:HIV Reverse Transcriptase