Mechanisms of clinical resistance by HIV-I variants to zidovudine and the paradox of reverse transcriptase sensitivity.

Even with the development of novel nucleoside analog inhibitors, zidovudine (AZT or 3'-azido-3'-deoxythymidine) remains a potent and frequently prescribed antiretroviral therapy for HIV-positive individuals. Failure of AZT in monotherapy due to the emergence of drug-resistant virus has not excluded it from use in most combination therapies with other nucleoside analogs, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. Thus, an understanding of the mechanism of AZT resistance could be the key in predicting the failure of many treatment strategies. In this review, the occurrence, characterization and ramification of AZT resistance in HIV-positive individuals will be discussed in the context of genotypic and phenotypic analyses of AZT-resistant viruses and reverse transcriptases. The mechanisms of resistance to AZT may be distinct from the mechanisms of resistance to other nucleoside analogs.