ANTIRETROVIRAL ACTIVITY OF STAVUDINE (2',3'-DIDEHYDRO-3'-DEOXYTHYMIDINE, D4T)

Stavudine, 2',3'-didehydro-3'-deoxythymidine (D4T), is a potent inhibi tor of HIV-1 reverse transcriptase in vitro. In clinical studies, stav udine has excellent oral bioavailability in excess of 80%. The dose-li miting toxicity is peripheral neuropathy, which occurred in 15% of sta vudine versus 6% of zidovudine-treated patients for 80 weeks in a rand omized, blinded, phase III trial. Stavudine-treated groups have experi enced significant increases in mean CD4 cell counts and decreases in b oth mean serum p24 antigen levels and infectious HIV titers in periphe ral blood mononuclear cells. In subjects with prior zidovudine treatme nt, the duration of these responses is limited; CD4 counts and serum p 24 antigen levels return to baseline after approximately 6 months. The effect of stavudine on clinical outcome and survival has not yet been established in comparative trials. Stavudine offers an additional the rapeutic option to those individuals who are refractory to or intolera nt of other available antiretrovirals.