stavudine

Stavudine, also known by the abbreviation d4T and sold under the brand name Zerit, is an antiretroviral medication in the nucleoside reverse transcriptase inhibitors (NRTIs) class. It is a thymidine analog that inhibits HIV reverse transcriptase by competing with natural nucleosides and causing chain termination when incorporated into viral DNA. It has activity against HIV-1 and is used as part of combination antiretroviral therapy (ART). Its role against hepatitis B is limited compared with other agents.

Stavudine is administered by mouth as part of combination ART regimens. Doses are given twice daily and are adjusted for renal function and body weight. In many high-income settings, stavudine has largely been replaced by less toxic NRTIs such as tenofovir or abacavir due to safety concerns. In resource-limited settings, stavudine has been used historically because of its low cost and wider availability, though its use is declining with global guidance favoring safer alternatives.

Common and serious adverse effects are a major consideration with stavudine. Long-term toxicity includes peripheral neuropathy, lipoatrophy, pancreatitis, hepatic steatosis, and lactic acidosis with potential liver enlargement. These mitochondrial toxicities can be dose- and duration-dependent and may be more likely in older patients or those with preexisting conditions. Because of these risks, many guidelines recommend phasing out stavudine in favor of regimens with more favorable safety profiles.

Pharmacologically, stavudine acts as a chain-terminating nucleoside analog and can encounter resistance through mutations in reverse transcriptase. Cross-resistance with other NRTIs can occur, and safety considerations influence its use in pregnancy and pediatric populations.