Tenofovir not toxic to mitochondria in human cell culture

Unlike nucleoside reverse transcriptase inhibitors (NRTIs) used to treat HIV infection, the nucleotide analogue tenofovir (Viread) is not associated with mitochondrial toxicity at concentrations well above those seen clinically, according to a report in the March issue of Antimicrobial Agents and Chemotherapy.

Many of the clinical toxicities associated with NRTIs have been attributed to their mitochondrial toxicity, the authors explain. Dr Tomas Cihlar and colleagues, from Gilead Sciences (the manufacturers of tenofovir) in Foster City, California, characterized the potential of tenofovir and currently used NRTIs to cause mitochondrial toxicity in various types of cells of human origin.

In concentrations ranging from 3 to 300 micromolar, tenofovir caused no significant changes in mitochondrial DNA levels in human hepatoblastoma cells, skeletal muscle cells, or renal proximal tubule epithelial cells, the authors report.

Along with abacavir (Ziagen) and lamivudine (Epivir), tenofovir was the least potent drug in inhibiting mitochondrial DNA synthesis, the report indicates, followed (in increasing order) by zidovudine (Retrovir), stavudine (Zerit), didanosine (Videx), and zalcitabine (Hivid).

Moreover, tenofovir increased extracellular lactate production by less than 20%, the results indicate, compared with two- to threefold increases by zidovudine and 30% to 50% increases by ddC.

“In summary, this study demonstrates that the potential of the anti-HIV nucleotide analogue tenofovir to induce mitochondrial toxicity in different human cell types is low,” the authors conclude. “These data are consistent with the favorable tolerability profile of tenofovir observed in HIV-infected patients.”