Introduction
Stribild is a fixed-dose combination antiretroviral medication used for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults. It contains four active components: elvitegravir (an integrase strand transfer inhibitor), cobicistat (a pharmacokinetic enhancer), emtricitabine (a nucleoside reverse transcriptase inhibitor), and tenofovir disoproxil fumarate (a nucleotide reverse transcriptase inhibitor). This single-tablet regimen offers simplified dosing that supports medication adherence.
Mechanism of Action
Stribild exerts its antiviral effect through three distinct mechanisms:
- Elvitegravir: Inhibits HIV-1 integrase, preventing the insertion of viral DNA into the host genome
- Emtricitabine: A cytosine analog that inhibits HIV-1 reverse transcriptase by competing with natural substrate deoxycytidine triphosphate and incorporating into viral DNA causing chain termination
- Tenofovir disoproxil fumarate: Converted to tenofovir, an adenosine analog that inhibits HIV-1 reverse transcriptase by competing with natural substrate deoxyadenosine triphosphate and incorporating into viral DNA causing chain termination
- Cobicistat: Enhances elvitegravir exposure by inhibiting cytochrome P450 3A enzymes without intrinsic antiviral activity
Indications
Stribild is indicated for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg who:
- Are antiretroviral treatment-naïve
- Have virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components
Dosage and Administration
Standard dosing: One tablet taken orally once daily with food Administration: Must be taken with a meal (approximately 400 kcal) to ensure adequate absorption Missed dose: If missed within 18 hours of usual time, take with food as soon as possible. If more than 18 hours have passed, wait until next scheduled dose Special populations:- Renal impairment: Not recommended in patients with CrCl <70 mL/min
- Hepatic impairment: Not recommended in patients with severe hepatic impairment (Child-Pugh Class C)
- Pediatrics: Approved for patients ≥35 kg using adult dosing
- Geriatrics: Use with caution due to potential decreased renal function
- Pregnancy: Category B - use only if potential benefit justifies potential risk
Pharmacokinetics
Absorption: Elvitegravir and tenofovir absorption increased with food; peak concentrations achieved in 2-4 hours Distribution: All components extensively protein bound (>85%) Metabolism: Primarily hepatic via CYP3A (elvitegravir); cobicistat inhibits CYP3A, CYP2D6, and transporters Elimination:- Elvitegravir: Feces (94.5%) and urine (6.7%)
- Cobicistat: Feces (86%) and urine (8%)
- Emtricitabine: Urine (86%) and feces (14%)
- Tenofovir: Urine (70-80%) via glomerular filtration and active tubular secretion
Contraindications
- Concomitant use with drugs highly dependent on CYP3A for clearance and with narrow therapeutic indices (alfuzosin, cisapride, ergot derivatives, lovastatin, simvastatin, pimozide, sildenafil for pulmonary hypertension, triazolam, oral midazolam)
- Concomitant use with strong inducers of CYP3A (rifampin, St. John's wort)
- Patients with severe renal impairment (CrCl <70 mL/min)
- Patients with severe hepatic impairment
- Known hypersensitivity to any component
Warnings and Precautions
Boxed Warning:- Lactic acidosis/severe hepatomegaly with steatosis
- Exacerbations of hepatitis B following discontinuation
- New onset or worsening renal impairment including acute renal failure and Fanconi syndrome
- Immune reconstitution syndrome
- Bone effects: Decreased bone mineral density and increased fracture risk
- Fat redistribution
- Drug interactions due to CYP3A inhibition
Drug Interactions
Significant interactions:- Anticonvulsants: Carbamazepine, phenytoin, phenobarbital (decreased elvitegravir concentrations)
- Antimycobacterials: Rifabutin, rifapentine (decreased elvitegravir concentrations)
- Antacids: Separate administration by at least 2 hours
- H2-receptor antagonists/PPIs: May decrease elvitegravir absorption
- Other HIV medications: Not recommended with other antiretrovirals except as part of combination therapy
- HMG-CoA reductase inhibitors: Increased concentrations of atorvastatin, rosuvastatin; contraindicated with lovastatin, simvastatin
- Ergot derivatives: Contraindicated
- Phosphodiesterase-5 inhibitors: Increased concentrations; dose reduction recommended
Adverse Effects
Most common adverse reactions (>10%):- Nausea (16%)
- Diarrhea (12%)
- Headache, fatigue, abnormal dreams
- Rash, depression, insomnia
- Increased creatinine (due to cobicistat effect on tubular secretion)
- Decreased bone mineral density
- Lactic acidosis (rare but serious)
- Hepatotoxicity
- Renal impairment
Monitoring Parameters
Baseline:- HIV-1 RNA viral load
- CD4+ cell count
- Renal function (serum creatinine, CrCl, urinalysis)
- Hepatitis B and C serology
- Bone density (consider in patients with history of pathologic fracture)
- Pregnancy test (if applicable)
- HIV-1 RNA viral load at 2-4 weeks, then every 4-8 weeks until suppressed, then every 3-6 months
- CD4+ count every 3-6 months
- Renal function at 3 months, then every 6 months
- Liver function tests
- Bone density monitoring in high-risk patients
- Assessment for adherence and adverse effects at each visit
Patient Education
- Take exactly as prescribed with food
- Do not miss doses to maintain viral suppression
- Inform all healthcare providers about Stribild use
- Report any new symptoms, especially nausea, vomiting, abdominal pain, dark urine, jaundice, bone pain, or changes in urinary frequency
- Use effective contraception; discuss pregnancy plans with provider
- Understand risk of hepatitis B flare if discontinuing
- Regular follow-up and laboratory monitoring are essential
- Do not share medications or take other drugs without consulting healthcare provider
- Store at room temperature in original container
References
1. Stribild [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2023. 2. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. 2023. 3. Sax PE, DeJesus E, Crofoot G, et al. Coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 infection: week 144 results. J Acquir Immune Defic Syndr. 2020;83(3):310-318. 4. Mills A, Crofoot G, McDonald C, et al. Long-term safety and efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in HIV-1-infected adults. AIDS Res Hum Retroviruses. 2019;35(6):555-562. 5. Gallant JE, Daar ES, Raffi F, et al. Efficacy and safety of elvitegravir versus raltegravir in treatment-experienced patients: week 96 results. J Acquir Immune Defic Syndr. 2018;77(3):295-302.