Introduction
Genvoya is a fixed-dose combination antiretroviral medication used for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. It contains four active ingredients: elvitegravir (an integrase strand transfer inhibitor), cobicistat (a pharmacokinetic enhancer), emtricitabine (a nucleoside reverse transcriptase inhibitor), and tenofovir alafenamide (a nucleotide reverse transcriptase inhibitor). This single-tablet regimen offers simplified dosing and improved tolerability compared to earlier tenofovir disoproxil fumarate-based regimens.
Mechanism of Action
Genvoya combines four agents with complementary mechanisms of action:
- Elvitegravir: Inhibits HIV integrase, preventing integration of viral DNA into host genome
- Cobicistat: Inhibits cytochrome P450 3A enzymes, boosting elvitegravir concentrations
- Emtricitabine: Phosphorylated to active form that competes with deoxycytidine triphosphate
- Tenofovir alafenamide: Prodrug that hydrolyzes to tenofovir, then phosphorylated to active tenofovir diphosphate
Together, these components inhibit multiple stages of the HIV replication cycle, providing potent suppression of viral replication.
Indications
Genvoya is indicated for:
- Treatment of HIV-1 infection in adults and pediatric patients ≥35 kg
- Treatment-naïve patients
- Virologically suppressed patients (HIV-1 RNA <50 copies/mL) switching from a stable antiretroviral regimen
Dosage and Administration
Standard dosing: One tablet orally once daily with food Pediatric dosing: For patients ≥35 kg, same as adult dosing Renal impairment: Not recommended in patients with CrCl <30 mL/min Hepatic impairment: No dosage adjustment needed for mild-moderate impairment; not recommended in severe hepatic impairmentPharmacokinetics
Absorption: Bioavailability enhanced with food; Tmax: 2-4 hours Distribution: Extensive tissue distribution; protein binding varies by component (elvitegravir 98-99%, cobicistat 97-98%) Metabolism: Primarily hepatic via CYP3A (elvitegravir, cobicistat); minimal metabolism (emtricitabine, tenofovir alafenamide) Elimination: Half-lives: elvitegravir 12.9h, cobicistat 3.5h, emtricitabine 10h, tenofovir 0.51h Excretion: Feces (elvitegravir 94.8%, cobicistat 86.2%), urine (emtricitabine 70%, tenofovir <1%)Contraindications
- Concomitant use with drugs highly dependent on CYP3A for clearance with narrow therapeutic indices (alfuzosin, lovastatin, simvastatin)
- Concomitant use with strong CYP3A inducers (rifampin, St. John's wort)
- Patients with previous hypersensitivity to any component
- Coadministration with dabigatran etexilate in patients with CrCl <50 mL/min
Warnings and Precautions
Boxed Warning:- Lactic acidosis/severe hepatomegaly with steatosis
- Post-treatment acute exacerbation of hepatitis B
- New onset or worsening renal impairment
- Immune reconstitution syndrome
- Bone effects including decreased bone mineral density
- Fat redistribution
Drug Interactions
Significant interactions:- CYP3A substrates: Increased concentrations of midazolam, triazolam, ergot derivatives
- CYP3A inducers: Reduced elvitegravir concentrations (avoid rifampin, carbamazepine)
- Acid-reducing agents: Separate administration by 12 hours
- Anticoagulants: Monitor warfarin closely
- Anticonvulsants: Potential interactions with phenytoin, phenobarbital
- Herbal products: Avoid St. John's wort
Adverse Effects
Common adverse reactions (≥10%):- Nausea (12%)
- Diarrhea (7%)
- Headache (6%)
- Fatigue (5%)
- Lactic acidosis
- Severe hepatomegaly with steatosis
- Acute exacerbation of hepatitis B
- Renal impairment
- Decreased bone mineral density
Monitoring Parameters
Baseline:- HIV-1 RNA viral load
- CD4+ cell count
- Hepatitis B and C serology
- Renal function (serum creatinine, CrCl)
- Urinalysis
- Bone density assessment (if risk factors present)
- Viral load every 4-8 weeks until suppressed, then every 3-6 months
- CD4+ count every 3-6 months
- Renal function every 3-6 months
- Liver function tests
- Signs of lactic acidosis
- Bone health assessment
Patient Education
Key points:- Take exactly as prescribed with food
- Do not miss doses to maintain viral suppression
- Report any new symptoms, especially nausea, vomiting, abdominal pain
- Inform all healthcare providers about Genvoya use
- Use effective contraception; discuss pregnancy planning
- Understand potential drug interactions
- Regular follow-up and monitoring essential
- Not a cure for HIV; continues to prevent transmission risk
References
1. Genvoya [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2023. 2. Sax PE, et al. Lancet. 2015;385(9987):2606-2615. 3. Wohl DA, et al. J Acquir Immune Defic Syndr. 2016;73(3):294-302. 4. Mills A, et al. Lancet HIV. 2016;3(4):e158-e165. 5. FDA-approved labeling for Genvoya. Accessible via Drugs@FDA. 6. DHHS Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV.