Darunavir Ethanolate/Cobicistat/Emtricitabine/Tenofovir Alafenamide Fumarate

**Semantic type:** Pharmacologic Substance

**Definition:** A four-drug fixed combination of the ethanolate salt form of darunavir, a human immunodeficiency virus type 1 (HIV-1) protease nonpeptidic inhibitor; cobicistat, a cytochrome P450 3A (CYP3A) inhibitor; emtricitabine, a nucleoside reverse transcriptase (RT) inhibitor (NRTI) analog of cytidine; and tenofovir alafenamide fumarate, the fumarate salt form of the lipophilic phosphonamidate prodrug of tenofovir, a NRTI analog of adenosine monophosphate, that is used to treat human immunodeficiency virus (HIV) infection. Upon oral administration of darunavir ethanolate/cobicistat/emtricitabine/tenofovir alafenamide fumarate, darunavir selectively targets and binds to the active site of HIV-1 protease and inhibits the dimerization and catalytic activity of HIV-1 protease. This inhibits the proteolytic cleavage of viral Gag and Gag-Pol polyproteins in HIV-infected cells. This inhibition leads to the production of immature, non-infectious viral proteins that are unable to form mature virions, and prevents HIV replication. Cobicistat inhibits CYP3A, thereby limiting the oxidative metabolism of darunavir and increases its systemic exposure. Emtricitabine and tenofovir alafenamide, after being converted in vivo to tenofovir, inhibit the activity of HIV RT by competing with natural deoxyribonucleosides for incorporation into the growing viral DNA chain and resulting in early chain termination. This interferes with the generation of DNA copies of viral RNA, which is necessary for the synthesis of new virions.

**Synonyms:** - Symtuza