Single-tablet HIV regimen (PI + booster + 2× NRTI) Pregnancy: eMC §4.6: no or limited data (fewer than 300 pregnancy outcomes) from use of the combination in pregnant women; a moderate amount of data (300-1,000 outcomes) indicate no malformative or feto/neonatal toxicity of darunavir, cobicistat or tenofovir alafenamide, and a large amount of data (more than 1,000 exposed outcomes) indicate none for emtricitabine. However, darunavir/cobicistat during pregnancy results in low darunavir exposure (around 90% reduction in Cmin in the second and third trimesters), which may cause virological failure and increase the risk of mother-to-child transmission. Therefore therapy should NOT be initiated during pregnancy, and women who become pregnant on it should be switched to an alternative regimen. Breast-feeding: women should be instructed not to breast-feed while receiving this product, and women living with HIV are recommended not to breast-feed.

Darunavir with cobicistat, emtricitabine and tenofovir alafenamide

Brand names: Symtuza

A once-daily single-tablet four-drug regimen combining the protease inhibitor darunavir, the pharmacokinetic enhancer cobicistat, and the nucleos(t)ide reverse transcriptase inhibitors emtricitabine and tenofovir alafenamide, used as complete antiretroviral therapy for HIV-1 infection in adults and adolescents.

Adult dose

Dose: One tablet (darunavir 800 mg / cobicistat 150 mg / emtricitabine 200 mg / tenofovir alafenamide 10 mg) once daily, taken with food

Route: Oral - the tablet should not be crushed

Frequency: Once daily

eMC SPC §4.2 (Symtuza 800 mg/150 mg/200 mg/10 mg film-coated tablets). Therapy should be initiated by a physician experienced in the management of HIV-1 infection. POPULATION: the recommended dose regimen in adults and adolescents aged 12 years and older weighing at least 40 kg is one tablet once daily with food. ART-naive patients: one film-coated tablet once daily with food. ART-experienced patients: one tablet once daily with food may be used only in patients with prior antiretroviral exposure but WITHOUT darunavir resistance associated mutations (DRV-RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V, L89V) and who have plasma HIV-1 RNA < 100,000 copies/mL and CD4+ cell count >= 100 cells x 10^6/L; §4.4 states it should not be used in treatment-experienced patients with one or more DRV-RAMs, HIV-1 RNA >= 100,000 copies/mL, or CD4+ < 100 cells x 10^6/L. MISSED DOSE: if missed within 12 hours of the usual time, take the prescribed dose with food as soon as possible; if noticed later than 12 hours, skip it and resume the usual schedule. VOMITING: if the patient vomits within 1 hour of taking the dose, take another dose with food as soon as possible; if more than 1 hour after, no extra dose is needed until the next scheduled time. ELDERLY: limited information - use with caution above 65 years of age. HEPATIC IMPAIRMENT: no dose adjustment in mild (Child-Pugh A) or moderate (Child-Pugh B) impairment, but use with caution as the darunavir and cobicistat components are hepatically metabolised; must NOT be used in severe hepatic impairment (Child-Pugh C). PREGNANCY: therapy should not be initiated during pregnancy and women who become pregnant on it should be switched to an alternative regimen, because darunavir/cobicistat gives low darunavir exposure in pregnancy. HBV CO-INFECTION (§4.4): tenofovir alafenamide is active against hepatitis B virus; discontinuation in HIV/HBV co-infected patients may be associated with severe acute exacerbations of hepatitis - monitor clinically and with laboratory follow-up for at least several months after stopping; do not give concomitantly with products containing tenofovir disoproxil, lamivudine or adefovir dipivoxil. PAEDIATRIC: safety and efficacy in children aged 3-11 years, or weighing < 40 kg, have not yet been established (no data); must not be used in paediatric patients below 3 years of age because of safety concerns. Verify any under-18 use against a children's formulary. NOTE ON US LABELLING: the openFDA label in this bundle is a single-component darunavir (with ritonavir) label and does not describe this four-drug fixed combination; it was not used for the dose.

Dose adjustments

Renal

eMC §4.2: no dose adjustment required in patients with estimated glomerular filtration rate (Cockcroft-Gault) >= 30 mL/min. Should NOT be initiated in patients with eGFR-CG < 30 mL/min (no data), and should be discontinued if eGFR-CG declines below 30 mL/min during treatment.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substances or to any of the excipients (eMC §4.3)
Severe (Child-Pugh Class C) hepatic impairment
Co-administration with strong CYP3A inducers due to potential loss of therapeutic effect: carbamazepine, phenobarbital, phenytoin; rifampicin; lopinavir/ritonavir; St John's wort (Hypericum perforatum)
Co-administration with medicinal products carrying a risk of serious and/or life-threatening reactions: alfuzosin; amiodarone, dronedarone, ivabradine, quinidine, ranolazine; colchicine in patients with renal and/or hepatic impairment; rifampicin; ergot derivatives (dihydroergotamine, ergometrine, ergotamine, methylergonovine); dapoxetine; domperidone; naloxegol; pimozide, quetiapine, sertindole, lurasidone; elbasvir/grazoprevir; triazolam and orally administered midazolam; sildenafil when used for pulmonary arterial hypertension, avanafil; simvastatin, lovastatin and lomitapide; ticagrelor

Side effects

Diarrhoea - very common (22.6% in treatment-naive patients; 10.5% in suppressed treatment-experienced patients) (eMC §4.8)
Headache (13.1% naive / 10.4% experienced) - very common; dizziness common
Rash (12.7% naive / 5.1% experienced) - very common, including macular, maculopapular, papular, erythematous, pruritic and generalised rash and allergic dermatitis; pruritus and urticaria common, angioedema uncommon, DRESS and Stevens-Johnson syndrome rare, toxic epidermal necrolysis and acute generalised exanthematous pustulosis frequency not known
Nausea (9.7%), fatigue (8.0%), abdominal pain (5.8%), arthralgia (7.7% in experienced patients) - common; also vomiting, abdominal distension, dyspepsia, flatulence, myalgia, anaemia
Metabolic and hepatobiliary: diabetes mellitus, anorexia, hypercholesterolaemia, increased low density lipoprotein, hypertriglyceridaemia, hyperlipidaemia, dyslipidaemia and hepatic enzyme increased (common); hyperglycaemia, acute pancreatitis, pancreatic enzymes increased, acute hepatitis, cytolytic hepatitis, osteonecrosis, immune reconstitution inflammatory syndrome (uncommon); crystal nephropathy (rare)

Interactions

Strong CYP3A inducers (carbamazepine, phenobarbital, phenytoin, rifampicin, lopinavir/ritonavir, St John's wort) - contraindicated, loss of therapeutic effect (eMC §4.3)
CYP3A-dependent medicines with narrow safety margins (alfuzosin, ergot derivatives, orally administered midazolam, triazolam, pimozide, quetiapine, sertindole, lurasidone, simvastatin, lovastatin, lomitapide, ticagrelor, ranolazine, ivabradine, dronedarone, amiodarone, quinidine, naloxegol, domperidone, dapoxetine, avanafil, sildenafil for pulmonary arterial hypertension, elbasvir/grazoprevir) - contraindicated (eMC §4.3)
Colchicine - contraindicated in patients with renal and/or hepatic impairment (eMC §4.3)
Medicinal products containing tenofovir disoproxil (fumarate, phosphate or succinate), lamivudine, or adefovir dipivoxil used for HBV infection - must not be given concomitantly (eMC §4.4)
Parenterally administered midazolam requires caution rather than being contraindicated (eMC §4.3/§4.5).
This interaction list may be incomplete — check the full SPC.

Clinical monograph

How it works

Darunavir inhibits HIV protease to prevent maturation of viral particles while cobicistat boosts its levels by inhibiting CYP3A; emtricitabine and tenofovir alafenamide are incorporated into viral DNA by reverse transcriptase, causing chain termination.

Prescribing in practice

Cobicistat is a potent CYP3A inhibitor that causes numerous serious drug interactions, so screen all co-medications (including statins, ergot derivatives, certain sedatives, antiarrhythmics and the contraceptive pill) before and during therapy.
Darunavir is a sulfonamide derivative, so use with caution in patients with a known sulfonamide allergy and monitor for rash.
Cobicistat inhibits tubular creatinine secretion, producing a small early rise in serum creatinine without a true fall in glomerular filtration, which should not be mistaken for renal impairment.

Monitoring

Monitor HIV viral load and CD4 count to confirm virological response, alongside renal function, liver function and lipids during treatment.

Counselling the patient

Take the tablet once daily with food to optimise absorption.
Do not start any new medicine, including herbal remedies such as St John's wort, without checking for interactions.
Continue taking every day to keep the virus suppressed and reduce the risk of resistance.

Evidence & guidelines

Use of antiretroviral therapy in HIV is guided by BHIVA and NICE recommendations, with treatment selected and monitored by specialist HIV services.

Reference: BHIVA HIV guidelines; EACS; Confirm identity and dosing against the manufacturer SPC (eMC) and NICE. Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways