Tenofovir disoproxil fumarate (TDF), a prodrug of tenofovir, is a nucleotide reverse transcriptase inhibitor. It is administered orally at 300 mg once daily in combination with an additional nucleoside reverse transcriptase inhibitor (NRTI), typically emtricitabine, and an additional antiretroviral such as a non-nucleoside reverse transcriptase inhibitor (NNRTI), an integrase inhibitor or a protease inhibitor (PI). After hydrolysis in the lumen of the gastrointestinal tract, tenofovir is taken up by cells and subsequently phosphorylated to the active tenofovir-diphosphate (TFV-DP) moiety. TFV-DP is incorporated into viral DNA and terminates DNA elongation. Tenofovir is excreted by the kidneys through glomerular filtration and tubular secretion. Although few drug-drug interactions occur, tenofovir plasma concentrations may increase in the presence of other renally eliminated drugs. Safety and efficacy of TDF have been demonstrated in treatment-naïve and treatment-experienced patients. Although generally well tolerated, some studies suggest an increased risk for adverse events, such as bone toxicity and/or nephrotoxicity with long term TDF use. Patient adherence to TDF-containing regimens is improved over other antiretrovirals due to its once daily administration and low toxicity profile. Its use as pre-exposure prophylaxis against HIV is currently being investigated.
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