Genvoya
Genvoya
Generic Name
Genvoya
Mechanism
Elvitegravir – an integrase strand transfer inhibitor that blocks the enzymatic activity of HIV integrase, preventing insertion of viral DNA into the host genome.
Cobicistat – a pharmacokinetic enhancer that is a CYP3A4 inhibitor; it boosts elvitegravir plasma exposure without antiviral activity.
Emtricitabine – an NRTI that incorporates into viral DNA and terminates chain elongation.
Tenofovir alafenamide – a prodrug of tenofovir; intracellular activation to tenofovir diphosphate leads to chain termination of reverse‑transcribed viral DNA.
*Net effect:* multi‑class coverage targeting reverse transcription and integration, with a single daily tablet.
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Pharmacokinetics
| Parameter | Key Point |
| Absorption | Rapid; peak plasma concentrations 1–1.5 h post‑dose. Food has minimal impact. |
| Distribution | Moderate protein binding (~27 %); volume of distribution ~365 L (elvitegravir). |
| Metabolism | Elvitegravir and cobicistat primarily metabolized by CYP3A4; cobicistat is a strong inhibitor, so it reduces elvitegravir metabolism. |
| Elimination | Renal excretion of tenofovir diphosphate metabolites; steady‑state plasma t½: elvitegravir ~4 h, emtricitabine ~10 h, TAF ~5–9 h. |
| Drug Interactions | Concomitant CYP3A4 inducers (e.g., rifampin, carbamazepine) lower elvitegravir levels; strong inhibitors (e.g., ketoconazole) require dose adjustment of the fixed‑dose. |
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Indications
- Primary therapy for adult patients with newly diagnosed HIV‑1 infection when a single‑tablet regimen is desired.
- Optional second‑line switch therapy in virologically suppressed patients if no resistance to components.
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Contraindications
- Contraindications
- Hypersensitivity to any component.
- Severe hepatic impairment (Child‑Pugh C).
- Renal insufficiency with eGFR < 30 mL/min/1.73 m² (due to tenofovir).
- Warnings
- Hepatotoxicity – monitor ALT/AST; severe elevations warrant discontinuation.
- Cardiovascular – potential QT prolongation when combined with QT‑prolonging drugs.
- Bone/Cartilage – long‑term TAF exposure may lower bone mineral density; consider baseline DEXA.
- Drug–Drug Interactions – avoid co‑administration with strong CYP3A inducers (e.g., rifampin, carbamazepine).
- Pregnancy – category C; avoid in pregnancy unless no alternatives.
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Dosing
- Standard dose: one 88 mg elvitegravir/200 mg cobicistat/200 mg emtricitabine/100 mg tenofovir alafenamide tablet (Genvoya 3 tab) once daily.
- Always: administer with food to enhance absorption; strict 24 h dosing interval.
- Switching: Can replace existing 3‑tab regimen without overlap if drug levels are comparable.
- Rescue therapy: If treatment interruption >48 h, restart at full dose; no loading dose required.
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Adverse Effects
| Adverse Effect | Commonality | Severity |
| Nausea, vomiting | ≥ 5 % | Mild–moderate |
| Headache, dizziness | ≥ 4 % | Mild |
| Insomnia | ≤ 3 % | Mild |
| Elevated ALT/AST | < 2 % | Serious if > 10× ULN |
| QTc prolongation | < 1 % | Serious if > 500 ms or symptomatic |
| Hypersensitivity rash | < 1 % | Severe if systemic |
| Renal dysfunction (creatinine rise) | Rare | Serious |
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Monitoring
- Baseline: CBC, CMP (incl. ALT/AST, eGFR), HIV viral load, CD4⁺ count, pregnancy test (females).
- Every 4–12 weeks: CBC, CMP, HIV RNA, CD4⁺; after 6 months, DEXA if risk factors for osteoporosis.
- ECG: if concomitant QT‑prolonging medication; periodic review for patients with cardiac disease.
- Serum phosphate: optional if renal impairment or advanced HIV disease.
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Clinical Pearls
- Fixed‑Dose Convenience – Genvoya’s single‑tablet daily dosing improves adherence compared with multi‑tab PI or NNRTI regimens.
- Cobicistat Suppression – Because cobicistat is a potent CYP3A inhibitor, co‑administration with drugs that are CYP3A substrates (e.g., lamotrigine) can lead to toxicity; dose adjustments or alternative agents are required.
- Kidney‑Friendly Tenofovir – TAF delivers tenofovir diphosphate to cells efficiently, enabling lower plasma tenofovir levels and reduced nephrotoxicity versus TDF.
- Avoid With Strong Inducers – Rifampin, St. John’s Wort, carbamazepine, or phenobarbital must be avoided; if unavoidable, consider a PI‑based regimen instead.
- Watch for Fatigue & Weakness – These can mask early renal dysfunction; vigilant monitoring of eGFR is essential, especially in elderly or concomitant nephrotoxic drugs.
- Neurotoxicity? – Unlike other integrase inhibitors (e.g., dolutegravir), elvitegravir has a low incidence of peripheral neuropathy; reassuring for patients with pre‑existing neuropathies.
Key Takeaway: Genvoya is a highly potent, once‑daily, four‑component ART that balances efficacy with a favorable safety profile, but requires careful attention to drug interactions, renal function, and hepatic status.