What to Know About Genvoya (Elvitegravir, Cobicistat, Emtribitabine, Tenofovir AF)

Genvoya, also referred to as the Quad pill, is an all-in-one tablet used to treat HIV in adults and older children. Taken daily, Genvoya is comprised of four different antiretroviral drugs:

• Elvitegravir, an integrase inhibitor
• Cobicistat, an HIV "booster" drug
• Emtricitabine, a nucleoside reverse transcriptase inhibitor (NRTI)
• Tenofovir alafenamide (TAF), another NRTI

Genvoya is the first combination pill to use TAF, an "improved" version of tenofovir disoproxil fumarate (TDF) found in the drugs Truvada, Atripla, and Complera. As such, Genvoya can be considered an improvement on Stribild, the single-tablet formulation comprised of elvitegravir + cobicistat + emtricitabine + TDF. 

TAF is regarded as superior to TDF as it is a prodrug, meaning a substance that is metabolized in the body to produce a drug. Because of this, TAF requires a far smaller dose and is less likely to cause kidney impairment experienced by some users of TDF.

Antiretroviral drugs do not cure HIV. Instead, the drugs work by blocking a stage in the virus's replication cycle. By doing so, the virus can be suppressed to undetectable levels and prevent disease progression.

With Genvoya, two stages are blocked: reverse transcription, in which viral RNA is converted into DNA, and integration, in which the DNA is integrated into the host cell's nucleus to "hijack" the genetic machinery so that the virus can churn out new copies of itself.

Uses

Genvoya is used to treat HIV infection. The fixed-dose combination tablet was approved by the U.S. Food and Drug Administration in November 2015 for use in adults and children 12 and over who have never been on antiretroviral therapy and weigh over 77 pounds, (35 kilograms).

Genvoya can also be used to replace an antiretroviral drug regimen as long as the person has an undetectable viral load.

There are no off-label uses for Genvoya or generic versions of the drug.

Before Taking

Before taking Genvoya, your doctor will order tests if you have never been on antiretrovirals or are changing treatment. The primary aim of the tests is to ensure you not resistant to any of the drugs in Genvoya (or any other antiretroviral therapy).

Because drug resistance can be transmitted, meaning passed from one person to the next, it is possible for a newly infected person to be resistant to certain antiretroviral drugs. The same can occur in anyone previously exposed to antiretrovirals, during which resistance can develop naturally over time.

The following tests can identify resistant mutations or the virus's susceptibility to various antiretroviral drugs:

• Genetic resistance testing: A blood test that can identify the number and types of mutations that confer resistance
• Phenotypic testing: A blood test used to isolate the virus so that it can be exposed to all available antiretroviral drugs to see which ones work bes

Precautions and Contraindications

Genvoya is contraindicated for use in anyone who has had a prior hypersensitive reaction to any of the drugs contained in the tablet.

Although Genvoya places less stress on the kidneys than TDF-based therapies, it is still used with caution in people with pre-existing kidney problems. Due to the lack of research, the FDA advises against the use of Genvoya in people with an estimated creatinine clearance below 30 milliliters per minute (mL/min).

Genvoya may also cause bone mineral loss. While this is generally not a problem for most people, bone mass density (BMD) tests should be performed in people with osteoporosis or a history of pathologic bone fractures to ensure they are appropriate candidates for the drug.

Other Combination Antiretroviral Drugs

In addition to Genvoya, there are 12 other combination drugs that can be taken in a once-daily dose:

• Atripla (efavirenz + FTC + TDF)
• Biktarvy (bictegravir + FTC + TAF)
• Complera (FTC + rilpivirine + TDF)
• Delstrigo (doravirine + lamivudine + TDF)
• Dovato (dolutegravir + lamivudine)
• Juluca (dolutegravir + rilpivirine)
• Odefsey (emtricitabine + rilpivirine + TAF)
• Stribild (cobicistat + elvitegravir + FTC + TDF)
• Symfi (efavirenz + lamivudine + TDF)
• Symfi Lo (efavirenz + lamivudine + TDF)
• Symtuza (cobicistat + darunavir + FTC + TAF)
• Triumeq (abacavir + dolutegravir + lamivudine

Dosage

Genvoya is manufactured as a green, oblong, film-coated tablet embossed with "GSI" on one side and with a "510" on the other. Each tablet contains 150 milligrams (mg) of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of TAF.

Genvoya is taken by mouth once daily with food. It should not be taken with any other antiretroviral drug used to treat HIV.

How to Take and Store

The drug elvitegravir requires food, specifically fats, for the drug to be properly absorbed in the gut. A high-fat meal is preferable to a low-fat meal.

Genvoya can be store at room temperature, ideally at or below 86°F (30°C). It is best to keep the tablets in their original light-resistant container in a dark, cool drawer or cabinet. Avoid storing Genvoya on a sunny windowsill or in your glove compartment. Discard any pills that have expired.

If you miss a dose of Genvoya, take it as soon as you remember. If it is near the time of your next dose, skip the original dose and continue as normal. Do not double up doses.

Side Effects

Genvoya is associated with fewer side effects than many of the earlier generation antiretroviral drugs. When they do occur, they tend to be mild and transient, resolving within one to two weeks of starting treatment.

Common

According to premarket research, the most common side effects of Genvoya use were (by order of frequency):

• Nausea (10% of users)
• Diarrhea (7% of users)
• Headache (6% of users)
• Fatigue (5% of users)

Severe

In rare instances, Genvoya has been known to cause severe side effects, leading to serious and potentially life-threatening complications such as:

• Kidney failure, most commonly in people with pre-existing kidney dysfunction
• Hepatomegaly, the abnormal enlargement of the liver seen associated with NRTIs, most commonly in people with pre-existing liver disease
• Osteomalacia, the softening of bone associated with tenofovir use
• Lactic acidosis, the potentially life-threatening build-up of lactic acid in the bloodstream

Warnings and Interactions

Genvoya carries a black box warning advising consumers and health professionals of the risk of severe hepatitis B exacerbation and hepatomegaly in users of the drug. The advisement is based largely on experience with TDF and NRTIs rather than TAF itself.

Genvoya is a Pregnancy Category B drug, meaning that animal studies have failed to show a risk of fetal harm but that well-controlled studies in humans are lacking.

Drug-Drug Interactions

Genvoya is known to interact with many drugs due to the competition for a liver enzyme called cytochrome P450 (CYP450). This is an enzyme that many drugs, including Genvoya, rely upon for metabolization.

The coadministration of drugs that are strong CYP450 inducers can lead to dramatic drops in drug concentration of Genvoya, reducing its effectiveness and increasing the risk of treatment failure.

Genvoya should not be taken with the following drugs or supplements:

• Antipsychotics: Orap (pimozide)
• Benzodiazepines: Halcion (triazolam), Versed (midazolam)
• Gastrointestinal motility drugs: Propulsid (cisapride)
• Hepatitis B drugs: Hepsera (adefovir)
• Migraine medications: DHE 45 (dihydroergotamine), Ergostat (ergotamine), Migergot (caffeine + ergotamine), Medihaler Ergotamine, Methergine (methylergotamine), and others
• Prostate medications: Uroxatral (alfuzosin)
• Pulmonary hypertension drugs: Revatio (sildenafil)
• St. John's wort
• Statin drugs: Mevacor (lovastatin), Pravachol (pravastatin), Zocor (simvastatin), and others
• Tuberculosis drugs: Mycobutin (rifabutin), Rifater (rifampin + isoniazid + pyrazinamide), Rifamate (rifampin + isoniazid), Rifadin (rifampin), Priftin (rifapentine), and others

Other drugs can interact with Genvoya and may require a drug substitution, dosage reduction, or the separation of doses by several hours.