Tenofovir alafenamide (TAF) as the successor of tenofovir disoproxil fumarate (TDF)

• Published in: Biochemical pharmacology 2016-11, Vol.119, p.1-7
• Main Author: De Clercq, Erik
• Format: Article
• Language: English
• Subjects: Adenine - administration & dosage; Adenine - analogs & derivatives; Adenine - economics; Adenine - therapeutic use; Antiviral Agents - administration & dosage; Antiviral Agents - economics; Antiviral Agents - therapeutic use; HBV (hepatitis B virus); HIV (human immunodeficiency virus); HIV Infections - drug therapy; HIV Infections - prevention & control; Humans; TAF (tenofovir alafenamide); TDF (tenofovir disoproxil fumarate); Tenofovir - administration & dosage; Tenofovir - economics; Tenofovir - therapeutic use; TFV (tenofovir)
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2016.04.015

[Display omitted] Tenofovir alafenamide (TAF) can be considered a new prodrug of tenofovir (TFV), as successor of tenofovir disoproxil fumarate (TDF). It is in vivo as potent against human immunodeficiency virus (HIV) at a 30-fold lower dose (10mg) than TDF (300mg). TAF has been approved in November 2015 (in the US and EU), as a single-tablet regimen (STR) containing 150mg elvitegravir (E), 150mg cobicistat (C), 200mg emtricitabine [(−)FTC] (F) and 10mg TAF, marketed as Genvoya®, on 01 March 2016 in the US as an STR containing 25mg rilpivirine (R), 200mg F and 25mg TAF, marketed as Odefsey®, and on 4 April 2016 in the US, as an STR containing 200mg F and 25mg TAF, marketed as Descovy®, for the treatment of HIV infections. STR combinations containing TAF and emtricitabine could be paired with a range of third agents, for example, darunavir and cobicistat. TAF has a much lower risk of kidney toxicity or bone density changes than TDF, and also offers long-term potential in the pre-exposure prophylaxis (PrEP) of HIV infections. TAF is specifically accumulated in lymphatic tissue, and in the liver, and hence also holds great potential for the treatment of hepatitis B virus (HBV) infections. Akin to TDF, TAF is converted intracellularly to TFV. Its active diphosphate metabolite (TFVpp) is targeted at the RNA-dependent DNA polymerase (reverse transcriptase) of either HIV or HBV.