دانلود رایگان مقاله آلوفین امید تنوفوویر به عنوان جانشین فومارات تنوفوویر دیسوپروکسیل

Abstract

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 (10 mg) than TDF (300 mg). TAF has been approved in November 2015 (in the US and EU), as a single-tablet regimen (STR) containing 150 mg elvitegravir (E), 150 mg cobicistat (C), 200 mg emtricitabine [(−)FTC] (F) and 10 mg TAF, marketed as Genvoya®, on 01 March 2016 in the US as an STR containing 25 mg rilpivirine (R), 200 mg F and 25 mg TAF, marketed as Odefsey®, and on 4 April 2016 in the US, as an STR containing 200 mg F and 25 mg 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.

14. Conclusions

The highlights of TAF could be summarized as follows: (i) TAF is equally potent as an antiretrovirus agent at a 30-fold lower dose (10 mg as compared to 300 mg) than TDF. This reduces the risk of toxicity for TAF by a factor of 30-fold as well. (ii) In fact, TAF, as compared to TDF, has been shown to signifi- cantly reduce kidney (glomerular and tubular) disturbances and bone mineral (spine, hip) density changes. (iii) TAF should also offer a reduced risk of these kidney and bone side effects when used for PrEP, for which TDF in combination with (
)FTC (emtricitabine) (marketed as Truvada
) has been approved in the US since 2012. (iv) Akin to TDF, TAF leads to little or negligible emergence of drug resistance (to tenofovir), and this is likely to be further decreased given the lower dosage of TAF as compared to TDF. (v) TAF, due to its antiretrovirus potency, combined with its virtually complete safety, might form the cornerstone for longterm, or even lifelong use, in the treatment of HIV infections. (vi) TAF has so far been approved for clinical use in combination with elvitegravir, cobicistat and emtricitabine (marketed as Genvoya
), with emtricitabine (marketed as Descovy
) and with rilpivirine and emtricitabine (marketed as Odefsey
), and this use is likely to be extended in the future to other combinations, including, i.e., darunavir. (vii) TAF not only shows promise for the treatment and prevention of HIV infections, but also for the treatment of HBV infections.