dideoxycytidine

Dideoxycytidine, also known as 2',3'-dideoxycytidine and commercially as zalcititabine (brand name Hivid), is a nucleoside analogue of cytidine that was used as an antiretroviral medication. It belongs to the class of nucleoside reverse transcriptase inhibitors (NRTIs). The molecule is a 2',3'-dideoxyribonucleoside, meaning its sugar lacks the 2' and 3' hydroxyl groups. The active metabolite is the triphosphate form, produced intracellularly by host kinases, which competes with natural dCTP for incorporation by HIV reverse transcriptase.

Once incorporated into viral DNA, the lack of a 3' hydroxyl group terminates DNA chain elongation, thereby inhibiting viral replication. Dideoxycytidine is typically used in combination with other antiretrovirals; treatment regimens have varied over time as newer agents became available. Pharmacokinetics vary by route; it is administered orally, with activation to the triphosphate form by cellular kinases.

Historically, zalcititabine was approved in the early 1990s as part of combination antiretroviral therapy. However, it was associated with significant toxicity, including pancreatitis, peripheral neuropathy, lactic acidosis, anemia, neutropenia, and hepatotoxicity, leading to declines in use and withdrawal from many markets in favor of better-tolerated NRTIs.

Chemically related to other dideoxynucleosides such as didanosine, zalcititabine illustrated early challenges in antiretroviral therapy regarding toxicity and resistance. Resistance emerges via mutations in HIV reverse transcriptase that reduce incorporation of the analog.