Symtuza is a fixed-dose combination tablet containing darunavir, cobicistat, tenofovir alafenamide and emtricitabine.
Darunavir is a protease inhibitor also marketed as Prezista and in combination with cobicistat as Rezolsta. Cobicistat is a drug used as a boosting agent to increase the effect of darunavir. Tenofovir alafenamide and emtricitabine are from a class of drugs known as NRTIs (nucleoside/nucleotide reverse transcriptase inhibitors). They are also marketed as the combination tablet Descovy and included in the single-tablet regimens Odefsey, Genvoya and Biktarvy.
These drugs reduce the amount of HIV in the body, prevent the development of AIDS-defining illnesses and prevent HIV being passed on during sex when the viral load is undetectable.
Symtuza was approved in the United States in July 2018 and in the European Union in September 2017 for the treatment of HIV infection. Symtuza was approved on the basis of results from the EMERALD and AMBER studies.
The EMERALD study assessed the safety and efficacy of switching to Symtuza in virologically suppressed people taking a boosted protease inhibitor with tenofovir (tenofovir disoproxil fumarate (TDF) formulation) and emtricitabine. The study randomised 1141 people to continue with their existing boosted protease inhibitor regimen or switch to Symtuza. After 48 weeks there was no significant difference in the rate of viral rebound (2.5% vs 2.1%) or serious adverse events. (Orkin 2018)
The AMBER study compared Symtuza to darunavir, boosted by cobicistat, combined with tenofovir (TDF formulation) and emtricitabine in previously untreated people. The study randomised 725 people and followed them for 48 weeks, after which people in the TDF arm had the option to switch to Symtuza. At week 48, 91.4% of the Symtuza group had viral loads below 50 copies/ml compared to 88.4% of the control group. After week 48, 295 of 363 people in the control arm switched to Symtuza. At week 96, 85.1% of those randomised to Symtuza and 83.7% of those randomised to the control arm maintained a viral load below 50 copies/ml. (Orkin 2017; Orkin 2020)
Symtuza is taken as one yellow tablet once daily with food. Each tablet combines 800mg darunavir, 200mg emtricitabine and 10mg tenofovir alafenamide, along with 150mg cobicistat.
Common side effects of Symtuza include headache, diarrhoea, nausea (feeling sick), tiredness (fatigue), rash, allergic reaction (hypersensitivity), facial swelling, itching, loss of appetite, abnormal dreams, vomiting, abdominal pain, bloating, indigestion, flatulence, diabetes, raised lipid or liver or pancreatic enzyme or creatinine levels, dizziness, aching joints or muscles, feeling weak.
You must not take Symtuza with any of the following medicines:
- alfuzosin (treatment for prostate enlargement)
- amiodarone (treatment for angina and cardiac arrhythmia)
- avanafil (for erectile dysfunction)
- carbamazepine, phenobarbital, phenytoin (epilepsy and seizures)
- colchicine (if you have kidney/liver problems)
- dihydroergotamine or ergotamine (migraine)
- dronedarone, quinidine (cardiac arrhythmia)
- ergometrine or methylergonovine (after childbirth)
- lovastatin, simvastatin (lipid lowering)
- lurasidone, pimozide, quetiapine, sertindole (antipsychotic)
- midazolam (seizures)
- ranolazine (angina)
- rifampicin (tuberculosis)
- sildenafil (when used for pulmonary arterial hypertension)
- St John’s wort (anti-depressant)
- ticagrelor (blood thinner)
- triazolam (sedative).
Symtuza is not recommended for women who want to get pregnant, or who are pregnant. Darunavir boosted by cobicistat (in the product Symtuza) is not recommended for use during pregnancy owing to lower blood levels after week 12 of pregnancy, increasing the risk of treatment failure and mother-to-child transmission of HIV.
Symtuza can be taken by children aged 12 years and over, weighing 40kg or more.
Orkin C et al. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial. The Lancet HIV, 5: e23-e34 , 2018.
Orkin C et al. Week 48 results of AMBER: A Phase 3, randomised, double-blind trial in antiretroviral treatment (ART)-naïve HIV-1 infected adults to evaluate the efficacy and safety of the once-daily, single-tablet regimen (STR) of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) versus darunavir/cobicistat (DRV/c) plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). 16th European AIDS Conference, 25-27 October, Milan, abstract PS8/2, 2017.
Orkin C et al. Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. AIDS 34: 707-718, 2020.