Stavudine is a dideoxynucleoside used in the treatment of HIV infection. When HIV infects a cell, the virus first binds and fuses with the cell, releasing its nucleocapsid containing its RNA and reverse transcriptase into the cytosol of the cell. The reverse transcriptase converts the viral RNA into viral DNA in the cytosol. The viral DNA goes to the nucleus through the nuclear pore complex where it undergoes the process of transcription. The new viral RNA formed from transcription is transported back to the cytosol through the nuclear pore complex and translation occurs to produce viral proteins. These viral proteins are assembled and new HIV viruses bud from the cell. Stavudine enters the cell and is converted into stavudine monophosphate by thymidine kinase. Thymidylate kinase then converts stavudine monophosphate into stavudine diphosphate. Stavudine diphosphate is metabolized to stavudine triphosphate via nucleoside diphosphate kinase. Stavudine triphosphate is an analog of deoxyguanosine-5'-triphosphate (dGTP). Stavudine triphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with its substrate, dGTP and by incorporation into viral DNA. Stavudine triphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once stavudine triphosphate gets incorporated into DNA, this causes DNA chain termination, preventing the growth of viral DNA. Less viral proteins are therefore produced, and there is a reduction in new viruses being formed.

Stavudine Pathway (New) References