Tenofovir alafenamide

Tenofovir alafenamide is a novel tenofovir prodrug developed in order to improve renal safety when compared to the counterpart tenofovir disoproxil. Both of these prodrugs were first created to cover the polar phosphonic acid group on tenofovir by using a novel oxycarbonyloxymethyl linkers to improve the oral bioavailability and intestinal diffusion. Tenofovir alafenamide is an alanine ester form characterized for presenting low systemic levels but high intracellular concentration. It has been reported to produce a large antiviral efficacy at doses ten times lower than tenofovir disoproxil. Tenofovir alafenamide is indicated to treat chronic hepatitis B, treat HIV-1, and prevent HIV-1 infections.

Tenofovir alafenamide was developed by Gilead Sciences Inc and granted FDA approval on 5 November 2015.

Tenofovir alafenamide is indicated for the treatment of hepatitis B virus infection in adults and pediatric patients 12 years of age and older with compensated liver disease.

In combination with emtricitabine and other antiretrovirals, it is indicated for the treatment of HIV-1 infection in adolescent and adult patients with a weight higher than 35 kg. This combination is also indicated to prevent HIV-1 infections in high risk adolescent and adult patients, excluding patients at risk from receptive vaginal sex. When combined with antiretrovirals other than protease inhibitors that require a CYP3A inhibitor, it can be used to treat pediatric patients weighing 25-35 kg.

In the combination product with emtricitabine and bictegravir, tenofovir alafenamide is considered a complete treatment regimen for HIV-1 infections for treatment-naive patients or patients virologically suppressed for at least three months with no history of treatment failure.

Additionally, the combination product including elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide and the combination product including emtricitabine, rilpivirine and tenofovir alafenamide can be used in the treatment of HIV-1 infection in patients older than 12 years with no previous antiretroviral therapy history or who are virologically suppressed for at least 6 months with no history of treatment failure.

The combination product including darunavir, cobicistat, emtricitabine, and tenofovir alafenamide is indicated for the treatment of HIV-1 infection in adults without prior antiretroviral therapy or in patients virologically suppressed for 6 months and no reported resistance to darunavir or tenofovir.