Molecular Pharmacology of Nucleoside and Nucleotide HIV-1 Reverse Transcriptase Inhibitors

Renal Dysfunction due to Tenofovir-Diphosphate Inhibition of Mitochondrial Complex V (ATP Synthase)

“…In cells, tenofvoir is metabolized to its active diphosphate form by adenylate monophosphate kinase (tenofovir monophosphate) and 5′-nucleoside diphosphate (tenofovir diphosphate). 4 Renal injury is likely related to intracellular tenofovir accumulation in proximal tubule cells. A molecular mechanism of TDF-induced renal toxicity, however, is lacking, but it is thought to be via mitochondrial depletion and structural change, including size and shape changes, and leakage of mitochondrial proteins into the cytosol, with resultant DNA damage, which may even induce apoptosis of the cell.…”