General Information

Symtuza is a four-drug combination of darunavir, a human immunodeficiency virus (HIV-1) protease inhibitor, cobicistat, a CYP3A inhibitor, and emtricitabine and tenofovir alafenamide, both HIV-1 nucleoside analog reverse transcriptase inhibitors.

Symtuza is specifically indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults: • who have no prior antiretroviral treatment history or • who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 6 months and have no known substitutions associated with resistance to darunavir or tenofovir.

Symtuza is supplied as a tablet for oral administration. Symtuza is a four-drug fixed dose combination product containing 800 mg of darunavir (DRV), 150 mg of cobicistat (COBI), 200 mg of emtricitabine (FTC), and 10 mg of tenofovir alafenamide (TAF). The recommended dosage is one tablet taken orally once daily with food in adults. For patients who are unable to swallow the whole tablet, Symtuza may be split into two pieces using a tablet-cutter, and the entire dose should be consumed immediately after splitting.

Clinical Results

FDA Approval

The FDA approval of Symtuza was based on data from two 48-week, non-inferiority, pivotal Phase 3 studies that assessed the safety and efficacy of Symtuza versus a control regimen in adults with no prior ARV history (AMBER) and in virologically suppressed adults (EMERALD).

AMBER compared Symtuza to darunavir/cobicistat (D/C) plus emtricitabine/tenofovir disoproxil fumarate (F/TDF). The results demonstrated similar viral suppression rates (HIV-1 RNA <50c/mL at 48 weeks) between the darunavir-based single tablet regimen (STR) versus control (91.4% vs 88.4% respectively) and low virologic failure rates (HIV-1 RNA ≥50 c/mL; 4.4% vs. 3.3%) at 48 weeks.

The EMERALD study compared Symtuza to continuing treatment with a boosted protease inhibitor (bPI) plus emtricitabine and TDF. The trial found there were low virologic failure rates (HIV-1 RNA ≥50 c/mL; 0.8% vs. 0.5%) and high virologic suppression rates (HIV-1 RNA <50 c/mL; 94.9% vs. 93.7%) at Week 48, with no patients discontinuing the study due to virologic failure.

Side Effects

Adverse effects associated with the use of Symtuza may include, but are not limited to, the following:

diarrhea

rash

nausea

fatigue

headache

abdominal discomfort

flatulence

The Symtuza drug label comes with the following Black Box Warning: Severe acute exacerbations of hepatitis B (HBV) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of Symtuza. Hepatic function should be monitored closely in these patients. If appropriate, anti-hepatitis B therapy may be warranted.