Strains of HIV which are resistant to AZT can persist at least a year and a half after treatment with the drug is discontinued, according to French study published in the September 2002 edition of the Journal of Medical Virology.
Investigators at the Hopital Europeen Georges Pompidou in Paris conducted a prospective study of 66 people who had developed resistance to AZT when used in HAART combinations, at condons 41 and 215 of the reverse transcriptase gene.
Even when the study participants were switched to either a dual or triple HAART regimen and experienced a fall in viral load to below the limits of detection, resistance to AZT at codon 215 persisted for up to 20 months, with 93.5% of the study sample having the mutation at baseline and 96.3% at 12 to 20 months.
The study authors speculate that the persistence of AZT resistance may have two complementary causes: the continued selection of thymidine analogue resistance mutations by regimens which normally included d4T, and the effect of the new regimens in suppressing viral load may have inhibited the replacement of less fit HIV mutations by fitter variants.
In conclusion the authors note that “at least fifteen months following discontinuation” of AZT, “effective antiretroviral therapy is insufficient to allow for ZDV (AZT) resistant strains to disappear, and thus allow for the safe re-introduction of the drug.”
Belec L et al. Sustained high proportion of zidovudine-resistant HIV variants despite prolonged substitution of zidovudine by other nucleoside reverse transcritpase inhibitors. Journal of Medical Virology, 68: 1, 1-6, 2002.