Comparison Of Metabolism And In Vitro Antiviral Activity Of Stavudine Versus Other 2',3'-Dideoxynucleoside Analogues

2',3'-dideoxynucleosides are the principal drugs used to treat AIDS and are the only drugs thus far with demonstrated clinical benefits in patients with human immunodeficiency virus (HIV) infection. Although nucleoside analogues are structurally similar and have common mechanisms of action, each drug has unique molecular, cellular, and clinical features. For example, 3'-azido-3'-deoxythymidine (zidovudine) and 3'-deoxy-2',3'-didehydrothymidine (stavudine) have similar in vitro anti-HIV activity but differ in their tendency to produce bone marrow suppression. Stavudine has been shown to be less myelosuppressive than zidovudine. With the exception of zidovudine, most of the clinically evaluated nucleoside analogues, including 2',3'-dideoxyinosine (didanosine), 2',3'-dideoxycytidine (zalcitabine), and stavudine, produce dose-dependent peripheral neuropathy. However, recent studies suggest that neuropathy induced by stavudine may be mediated by mechanisms different from those of didanosine and zalcitabine.