ABSTRACT
Nucleoside reverse transcriptase inhibitors (NRTIs) include thymidine analogs such as stavudine (d4T) and zidovudine (AZT or ZDV); cytosine analogs such as emtricitabine (FTC), lamivudine (3TC), and zalcitabine (ddC); the inosine derivative didanosine (ddI); and the guanosine analog abacavir sulfate (ABC). Tenofovir disoproxil fumarate (TDF or PMPA) is an adenosine-derived nucleotide reverse transcriptase inhibitor. As a class, NRTIs require stepwise phosphorylation to the 50-triphosphate, which is their pharmacologically active moiety. This intracellular phosphorylation occurs by cytoplasmic or mitochondrial kinases and phosphotransferases. The active triphosphate then inhibits viral replication through competitive binding to the viral enzyme reverse transcriptase and chain reaction termination after incorporation into the proviral DNA due to the modified 30hydroxyl group (1,2). The triphosphate anabolite is also a potential source of toxicity through inhibition of mitochondrial DNA polymerase (3).
