MECHANISMS OF CLINICAL RESISTANCE BY HIV-I VARIANTS TO ZIDOVUDINE ANDTHE PARADOX OF REVERSE-TRANSCRIPTASE SENSITIVITY

Even with the development of novel nucleoside analog inhibitors, zidov udine (AZT or 3'-azido-3'-deoxythymidine) remains a potent and frequen tly prescribed antiretroviral therapy for HIV-positive individuals. Fa ilure of AZT in monotherapy due to the emergence of drug-resistant vir us has not excluded it from use in most combination therapies with oth er nucleoside analogs, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. Thus, an understanding of the mechanism of A ZT resistance could be the key in predicting the failure of many treat ment strategies. In this review, the occurrence, characterization and ramification of AZT resistance in HIV-positive individuals will be dis cussed in the context of genotypic and phenotypic analyses of AZT-resi stant viruses and reverse transcriptases,The mechanisms of resistance to AZT may be distinct from the mechanisms of resistance to other nucl eoside analogs.