Tenofovir alafenamide



Tenofovir alafenamide (trade name Vemlidy) is a nucleotide reverse transcriptase inhibitor and a prodrug of tenofovir. It was developed by Gilead Sciences based on the protide technology of Chris McGuigan for use in the treatment of HIV infection and chronic hepatitis B, and is applied in the form of tenofovir alafenamide fumarate (TAF). Closely related to the commonly used reverse-transcriptase inhibitor tenofovir disoproxil fumarate (TDF), TAF has greater antiviral activity and better distribution into lymphoid tissues than that agent. Vemlidy was approved by the U.S. Food and Drug Administration (FDA) in November 2016.

Gilead announced a Phase III clinical trial evaluating a single-tablet regimen combining tenofovir alafenamide with cobicistat, emtricitabine and elvitegravir and developed a coformulation of the drug with cobicistat, emtricitabine and the protease inhibitor darunavir. In a 48-week study comparing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil (trade name Stribild) to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (trade name Genvoya), the results showed the newer drug to be noninferior to the established agent, but at much lower dosages and with lower incidence of adverse side effects such as impaired kidney function. The FDA approved the TAF-based treatment regimen for treatment of HIV-1 in November 2015. Genvoya is the first TAF-based regimen to receive approval.

Fixed-dose combinations containing tenofovir alafenamide

 * Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (trade name Genvoya) — approved November 5, 2015 (compare Elvitegravir/cobicistat/emtricitabine/tenofovir; trade name Stribild)
 * Emtricitabine/rilpivirine/tenofovir alafenamide (trade name Odefsey) — approved March 1, 2016 (compare Emtricitabine/rilpivirine/tenofovir; trade name Complera)
 * Emtricitabine/tenofovir alafenamide (trade name Descovy) — approved April 4, 2016 (compare Emtricitabine/tenofovir; trade name Truvada). In October 2019, Descovy was approved in the United States for HIV-1 pre-exposure prophylaxis (PrEP).
 * Bictegravir/emtricitabine/tenofovir alafenamide (trade name Biktarvy) — approved 2018.
 * Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (trade name Symtuza) — approved July 17, 2018