Genvoya (Elvitegravir / Cobicistat / Emtricitabine / Tenofovir Alafenamide)

What Is Genvoya and What Is It Used For?

Genvoya is a single-tablet antiretroviral medication containing elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (E/C/F/TAF). It is used for the treatment of HIV-1 infection in adults and children weighing at least 25 kg. Genvoya must be taken once daily with food.

Genvoya belongs to a class of medications known as antiretroviral agents, specifically combining an integrase strand transfer inhibitor (INSTI) with a pharmacokinetic enhancer and two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). It was first approved by the European Medicines Agency (EMA) in 2015 and by the U.S. Food and Drug Administration (FDA) the same year. It is manufactured by Gilead Sciences and is one of several single-tablet regimens available for HIV treatment.

The four active ingredients in Genvoya each play a distinct role in suppressing HIV replication. Elvitegravir blocks HIV integrase, an enzyme the virus needs to insert its genetic material into the DNA of human immune cells. Cobicistat does not have direct antiviral activity but acts as a pharmacokinetic enhancer (booster) by inhibiting the CYP3A enzyme system, thereby increasing and maintaining blood levels of elvitegravir. Emtricitabine and tenofovir alafenamide are both NRTIs that block HIV reverse transcriptase, another essential enzyme the virus requires for replication.

By targeting multiple stages of the HIV lifecycle simultaneously, Genvoya provides potent viral suppression and maintains a meaningful barrier to the development of drug resistance. In clinical trials such as the GS-US-292-0104 and GS-US-292-0111 studies, Genvoya demonstrated non-inferior virologic efficacy compared to the older combination containing tenofovir disoproxil fumarate (TDF), with improved safety profiles relating to bone mineral density and renal biomarkers.

Who can take Genvoya?

Genvoya is approved for the treatment of HIV-1 infection in:

• Adults who are treatment-naive (starting HIV therapy for the first time) or treatment-experienced (switching from another regimen) with viral suppression (HIV-1 RNA <50 copies/mL) and no known resistance to the individual components
• Children and adolescents aged 6 years and older weighing at least 25 kg

Before starting Genvoya, your healthcare provider will assess your kidney function (estimated creatinine clearance must be at least 30 mL/min), check for hepatitis B co-infection, review your current medications for potential drug interactions, and perform HIV resistance testing to ensure the virus is susceptible to the components in Genvoya.

How does tenofovir alafenamide (TAF) differ from tenofovir disoproxil fumarate (TDF)?

Genvoya contains tenofovir alafenamide (TAF), a newer prodrug of tenofovir that is more efficiently taken up by cells, resulting in significantly lower circulating blood levels of tenofovir compared to TDF. This translates to less exposure of the kidneys and bones to tenofovir, which reduces the risk of renal tubular dysfunction and bone mineral density loss. In head-to-head clinical trials, patients receiving TAF-based regimens showed statistically significant improvements in bone density and renal markers compared to those on TDF-based regimens, while maintaining equivalent antiviral efficacy.

What Should You Know Before Taking Genvoya?

Before starting Genvoya, inform your doctor about all other medications, supplements, kidney problems, liver disease (especially hepatitis B), bone conditions, or if you are pregnant or planning to become pregnant. Several medications are contraindicated with Genvoya due to serious drug interactions.

Contraindications

Genvoya must not be used in the following circumstances:

• Co-administration with certain drugs: Genvoya must not be taken with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious or life-threatening events. These include alfuzosin, amiodarone, ergot derivatives (dihydroergotamine, ergotamine, methylergonovine), cisapride, oral midazolam, triazolam, pimozide, sildenafil (when used for pulmonary hypertension), lovastatin, simvastatin, lurasidone, and St. John's Wort.
• Strong CYP3A inducers: Rifampicin, rifabutin (at certain doses), carbamazepine, phenobarbital, and phenytoin must not be co-administered, as they significantly reduce elvitegravir and cobicistat levels and may lead to virologic failure and resistance.
• Hypersensitivity: Genvoya should not be used by patients with known hypersensitivity to any of the active substances or excipients.

Warnings and Precautions

Several important warnings apply to Genvoya therapy. Healthcare providers and patients should be aware of the following:

Lactic acidosis and severe hepatomegaly with steatosis: Nucleoside analogues, including emtricitabine and tenofovir alafenamide, have been associated with lactic acidosis (a dangerous build-up of lactic acid in the blood) and severe liver enlargement with fatty infiltration (hepatomegaly with steatosis), including fatal cases. Treatment should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.

Post-treatment exacerbation of hepatitis B: In patients co-infected with HIV-1 and hepatitis B virus (HBV), discontinuation of Genvoya may result in severe acute exacerbations of hepatitis B. Emtricitabine and tenofovir alafenamide are both active against HBV. If Genvoya is stopped in co-infected patients, hepatic function should be closely monitored for at least several months. Initiation of hepatitis B treatment may be warranted.

Kidney function: Although TAF has a more favorable renal safety profile than TDF, cases of renal impairment, including acute renal failure and Fanconi syndrome, have been reported with TAF-containing regimens. Kidney function (serum creatinine, estimated creatinine clearance, urine glucose, and urine protein) should be assessed before initiating therapy and monitored during treatment. Genvoya should not be initiated in patients with estimated creatinine clearance below 30 mL/min. If renal function declines during treatment, the cause should be sought and consideration given to adjusting or discontinuing therapy.

Immune reconstitution syndrome: When initiating antiretroviral therapy, patients whose immune system is severely compromised may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium complex, cytomegalovirus, Pneumocystis jirovecii pneumonia, or tuberculosis). Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barre syndrome) have also been reported in the setting of immune reconstitution, sometimes many months after treatment initiation.

Pregnancy and Breastfeeding

Current international guidelines, including those from the U.S. Department of Health and Human Services (DHHS) and the European AIDS Clinical Society (EACS), generally do not recommend Genvoya as a preferred regimen during pregnancy. This is primarily because cobicistat (the pharmacokinetic enhancer) has been shown to have lower blood levels during the second and third trimesters, which may result in inadequate boosting of elvitegravir and potential loss of virologic suppression.

Alternative regimens with more extensive pharmacokinetic and safety data during pregnancy (such as dolutegravir-based combinations) are generally preferred. If a patient becomes pregnant while taking Genvoya and has stable viral suppression, the decision to continue or switch should be made in close consultation with an HIV specialist, weighing the risks of virologic failure against the risks of changing therapy.

Breastfeeding is not recommended for people living with HIV in settings where safe formula feeding is available, because of the risk of transmitting HIV to the infant through breast milk. Both emtricitabine and tenofovir are known to be excreted in human breast milk.

How Does Genvoya Interact with Other Drugs?

Genvoya has numerous clinically significant drug interactions, primarily due to cobicistat's inhibition of CYP3A and certain drug transporters. Several medications are contraindicated, and many others require dose adjustments or close monitoring. Always inform your healthcare provider about every medication, supplement, and herbal product you take.

Cobicistat, the pharmacokinetic enhancer in Genvoya, is a potent inhibitor of CYP3A4 and also inhibits CYP2D6, as well as drug transporters including P-glycoprotein (P-gp), BCRP, MATE1, OATP1B1, and OATP1B3. These properties, while essential for boosting elvitegravir levels, mean that Genvoya can significantly alter the blood levels of many co-administered drugs, and conversely, strong CYP3A inducers can dramatically reduce the effectiveness of Genvoya.

Major Interactions (Contraindicated)

The following drugs must not be taken with Genvoya due to the risk of serious or life-threatening adverse events or loss of antiviral efficacy:

Interactions Requiring Dose Adjustment or Monitoring

Many additional medications require dose adjustments or enhanced monitoring when co-administered with Genvoya. Key examples include:

• Atorvastatin: Use the lowest effective dose; do not exceed 20 mg/day. Monitor for signs of myopathy.
• Amlodipine and other calcium channel blockers: Plasma levels may be increased; clinical monitoring recommended and dose reduction may be required.
• Clarithromycin: Levels of clarithromycin may be increased; consider alternatives for patients with renal impairment.
• Corticosteroids (inhaled/intranasal fluticasone, budesonide): Risk of Cushing's syndrome and adrenal suppression due to increased corticosteroid levels. Consider alternatives, particularly beclomethasone.
• Hormonal contraceptives: Norgestimate levels may be increased while ethinyl estradiol levels may be decreased. Consider alternative or additional contraceptive methods.
• Metformin: Monitor closely; cobicistat inhibits MATE1, potentially increasing metformin levels.
• Antacids and acid-reducing agents: Separate administration of antacids by at least 2 hours. Proton pump inhibitors and H2 receptor antagonists do not require separation.

What Is the Correct Dosage of Genvoya?

The recommended dose of Genvoya is one tablet taken once daily with food. The tablet contains elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg. The tablet should be swallowed whole and not crushed or split.

Adults

Genvoya should be taken at approximately the same time each day to maintain consistent drug levels. Adherence to the once-daily regimen is critical for maintaining viral suppression and preventing the emergence of drug-resistant mutations. Studies have shown that adherence rates above 95% are associated with optimal virologic outcomes in integrase inhibitor-based regimens.

Children and Adolescents

Elderly

No dose adjustment of Genvoya is required for elderly patients. However, caution is warranted because elderly individuals are more likely to have decreased renal function and may be taking multiple co-medications that could interact with Genvoya. Renal function should be monitored more closely in this population. Limited clinical data are available for patients over 65 years of age.

Renal Impairment

Missed Dose

If you miss a dose of Genvoya:

• Less than 18 hours since usual dosing time: Take the missed dose as soon as you remember, with food. Then take the next dose at the regular time.
• More than 18 hours since usual dosing time: Skip the missed dose entirely. Take the next scheduled dose at the usual time with food.
• Never take two doses at the same time or take extra doses to make up for a missed one.

If you vomit within 1 hour of taking Genvoya, take another tablet with food. If you vomit more than 1 hour after taking the dose, no additional dose is needed.

Overdose

There is limited clinical experience with overdose of Genvoya. If an overdose occurs, the patient should be monitored for signs of toxicity and standard supportive treatment applied. There is no specific antidote for Genvoya. Emtricitabine can be partially removed by hemodialysis (approximately 30% of the dose is removed over a 3-hour dialysis session). Elvitegravir is highly protein-bound and is unlikely to be significantly removed by hemodialysis. Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%.

What Are the Side Effects of Genvoya?

The most common side effects of Genvoya are nausea (affecting more than 1 in 10 patients), followed by diarrhea, headache, fatigue, and abnormal dreams. Most side effects are mild and tend to improve after the first few weeks. Serious but rare side effects include kidney problems, lactic acidosis, and liver toxicity.

Like all medicines, Genvoya can cause side effects, although not everybody gets them. Understanding which side effects are common and which are rare can help you recognise when to contact your healthcare provider. The following classification is based on clinical trial data and post-marketing surveillance reported in the EMA Summary of Product Characteristics and FDA prescribing information.

Metabolic and Body Composition Changes

Antiretroviral therapy, including Genvoya, may be associated with changes in body fat distribution (lipodystrophy). Patients may experience an increase in abdominal fat, breast enlargement, and wasting of fat in the face, limbs, and buttocks. The long-term health consequences of these changes are not fully understood. Additionally, some patients experience increases in blood cholesterol and triglyceride levels. Your healthcare provider will monitor your lipid profile regularly during treatment.

Weight gain has been observed in patients initiating antiretroviral therapy, particularly with integrase inhibitor-based regimens. In clinical studies, patients taking Genvoya gained an average of 1-3 kg during the first year of treatment. The clinical significance of this weight gain and its long-term implications are subjects of ongoing research.

When to Seek Medical Attention

Contact your healthcare provider immediately if you experience:

• Signs of lactic acidosis: unusual tiredness, muscle pain, difficulty breathing, stomach pain with nausea and vomiting, cold or blue extremities, fast or irregular heartbeat
• Signs of liver problems: yellowing of the skin or eyes (jaundice), dark urine, light-colored stools, loss of appetite, nausea
• Signs of kidney problems: decreased urine output, swelling in ankles or feet, unusual fatigue
• Signs of severe allergic reaction: difficulty breathing, swelling of the face, lips, tongue, or throat
• Signs of immune reconstitution syndrome: new or worsening symptoms shortly after starting treatment

How Should You Store Genvoya?

Store Genvoya in its original container at room temperature below 30°C (86°F). Keep the bottle tightly closed to protect from moisture. Keep a desiccant in the bottle. Do not remove the tablets from the original packaging for use in pill organizers with extended storage times.

Proper storage of Genvoya is essential to ensure the medication remains effective throughout its shelf life. The tablets are sensitive to moisture, and improper storage can compromise drug stability and potency. Follow these storage guidelines:

• Temperature: Store below 30°C (86°F). Do not freeze. Brief exposure to temperatures up to 40°C during transportation is acceptable, but prolonged exposure should be avoided.
• Moisture protection: Keep tablets in the original bottle with the desiccant canister (the small white cylinder inside the bottle). Do not swallow the desiccant. Keep the bottle tightly closed after each use.
• Light: Store in the original container to protect from excessive light exposure.
• Pill organizers: It is acceptable to use weekly pill organizers for short-term use (up to 7 days), but for longer periods, keep tablets in the original bottle.
• Expiration: Do not use Genvoya after the expiration date printed on the bottle. Discard any unused medication properly through your pharmacy's drug take-back program.

Keep Genvoya out of the reach and sight of children. Do not use the medicine if you notice any visible signs of deterioration or if the safety seal has been broken.

What Does Genvoya Contain?

Each Genvoya film-coated tablet contains four active ingredients: elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg (equivalent to tenofovir alafenamide fumarate 11.2 mg). The tablet also contains several inactive excipients.

Active Ingredients

• Elvitegravir 150 mg - an HIV-1 integrase strand transfer inhibitor (INSTI)
• Cobicistat 150 mg - a pharmacokinetic enhancer (CYP3A inhibitor)
• Emtricitabine 200 mg - a nucleoside reverse transcriptase inhibitor (NRTI)
• Tenofovir alafenamide 10 mg (as fumarate 11.2 mg) - a nucleotide reverse transcriptase inhibitor (NtRTI)

Inactive Ingredients (Excipients)

The tablet core contains: croscarmellose sodium, hydroxypropylcellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. The film coating contains: indigo carmine aluminium lake (E132), iron oxide yellow (E172), polyethylene glycol, polyvinyl alcohol (partially hydrolysed), talc, and titanium dioxide (E171).

The film-coated tablet is green, capsule-shaped, debossed with "GSI" on one side and "510" on the other side. It measures approximately 19 mm x 8.5 mm.