Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus.
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Ray AS, Fordyce MW, Hitchcock MJ
Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus.
Antiviral Res. 2016 Jan;125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27.
- PubMed ID
- 26640223 [ View in PubMed]
- Abstract
Despite substantial progress in the development of antiretroviral regimens that durably suppress Human Immunodeficiency Virus (HIV) infection, new agents that maintain high efficacy while further optimizing the safety of lifelong, chronic therapy are needed. Tenofovir alafenamide (TAF; formerly known as GS-7340) is a novel prodrug of the antiviral acyclic nucleoside phosphonate tenofovir (TFV) with improved properties relative to tenofovir disoproxil fumarate (TDF). Although potent and generally well tolerated, TDF therapy has been associated with changes in markers of renal function, decreases in bone mineral density and a rare occurrence of serious renal adverse events, including Fanconi's Syndrome. The renal and bone toxicity observed with TDF is associated with high circulating plasma levels of TFV. TAF was discovered to be a more efficient prodrug able to further refine HIV therapy and better address life-long therapy in an older and increasingly comorbid HIV infected population. By enhancing stability in biological matrices while being rapidly activated in cells, TAF produces higher levels of intracellular TFV diphosphate, the pharmacologically active metabolite, in HIV-target cells at substantially reduced oral doses of TFV equivalents. All TFV released in the body is eventually eliminated renally; therefore, lowering the TFV equivalents administered reduces off-target kidney exposure. Effective therapy is thus achieved at approximately 90% lower systemic exposure to TFV, translating to statistically and clinically significant improvement in safety parameters associated with bone mineral density and markers of renal function.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Tenofovir DNA polymerase Protein Human herpesvirus 2 (strain 186) YesInhibitorDetails Tenofovir Reverse transcriptase Protein HBV YesInhibitorDetails Tenofovir Reverse transcriptase/RNaseH Protein Human immunodeficiency virus 1 YesInhibitorDetails Tenofovir alafenamide DNA polymerase Protein Human herpesvirus 2 (strain 186) NoInhibitorDetails Tenofovir alafenamide Reverse transcriptase Protein HBV NoInhibitorDetails Tenofovir alafenamide Reverse transcriptase/RNaseH Protein Human immunodeficiency virus 1 YesInhibitorDetails