Reviewed by: HU Medical Review Board | Last reviewed: March 2023
Genvoya is a combination medication that contains elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide. It is used as a standalone antiretroviral therapy (ART) regimen for HIV-1 in adults and children who weigh at least 55 pounds (25 kg) who have never taken HIV medications before.
Individuals who have previously taken HIV medications can still take Genvoya, as long as they have no drug resistance mutations to any of the ingredients in Genvoya and have had a viral load (amount of HIV in the blood) of 50 copies per mL or less on a stable ART regimen for at least six months.
Although it is not a cure for HIV, when taken as directed, it allows for the virus to be suppressed. This prevents further transmission of HIV and allows an individual’s immune system to improve through increasing CD4 cell counts and decreasing the amount of active virus in the blood (viral load).
What are the ingredients in Genvoya?
The main ingredients in Genvoya are elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide. Elvitegravir is an integrase strand transfer inhibitor (INSTI, also known as an integrase inhibitor). Cobicistat is a CYP3A inhibitor, also referred to as a pharmacokinetic enhancer. Emtricitabine and tenofovir alafenamide are nucleoside reverse transcriptase inhibitors (NRTIs).
How does Genvoya work?
Genvoya is a combination of two NRTI medications, an integrase inhibitor, and a pharmacokinetic enhancer. NRTIs stop the reverse transcription step of the HIV life cycle. Normally, HIV uses its reverse transcriptase enzyme to build a strand of DNA from its original RNA form. In order to do this, it uses genetic building blocks called nucleosides that come from the host cell. These nucleosides are strung together one at a time, like beads on a string, to create the final DNA product.
How do NRTIs work?
NRTIs act as nucleoside mimics that stop the DNA-building process. NRTIs look like normal nucleosides, except they’re missing a special chemical group on one side. Without this group, the reverse transcriptase enzyme is unable to attach more nucleosides to the chain after them. This prevents the full string of DNA from being formed, preventing HIV RNA from making it all the way through the reverse transcription process and into host DNA for further replication.
How do integrase inhibitors work?
After HIV RNA is reverse transcribed into newly-formed DNA, it gets integrated into the host cell DNA using an enzyme called integrase. This allows HIV to be actively replicated with the rest of our DNA as our cell carries out its normal functions. Integrase inhibitors can be used to block the integrase enzyme and prevent the integration of HIV DNA into our host cells. If HIV’s DNA cannot be inserted into our host cells’ genome, the virus cannot continue to be replicated, assembled into mature virus particles, and released into the blood to continue infecting other cells.
How do pharmacokinetic enhancers work?
Pharmacokinetic enhancers don’t directly target and treat HIV. Instead, they inhibit an enzyme in the human body called cytochrome P450 3A4, also called CYP3A4. Normally, CYP3A4 helps break down drugs and other molecules in the body so that they can be eliminated. Drugs that get broken down, or metabolized, by this enzyme are prevented from staying in the body for too long.
However, when CYP3A4 is inhibited by a pharmacokinetic enhancer, it allows for the normal drug targets of this enzyme to continue to exist and work in the body beyond what’s normal. By preventing the breakdown enzyme from doing its job, the concentration and efficacy of other drugs, like elvitegravir, may be increased. All three medication types work together to prevent the overall progression of HIV through its life cycle.
Possible side effects
The most common side effect of Genvoya is nausea. This is not the only possible side effect of Genvoya. Talk to your doctor about what to expect when taking Genvoya. You also should call your doctor if you have any changes that concern you when taking Genvoya.
Things to note
Genvoya has a boxed warning, the strictest warning from the US Food and Drug Administration (FDA). It has this warning because of the possibility of serious side effects as described below.
As with any medication, there are several very rare but serious risks that need to be considered before taking Genvoya. Your healthcare provider can help determine what issues you may be at risk for and help determine what treatment options are the safest for you. It’s also important to remember that the risk of one or more of these issues occurring is low, and the benefits of treating the virus often greatly outweigh the risks.
Several of these rare but serious side effects of Genvoya include liver issues and an increase of lactic acid in the blood (lactic acidosis). Signs of liver issues include, but are not limited to:
- Dark-colored urine
- Loss of appetite
- Yellowing of the whites of the eyes or skin
- Light-colored bowel movements
- Pain or tenderness on the right side of your stomach
Signs of lactic acidosis include, but are not limited to:
- Trouble breathing
- Feeling cold, especially in the limbs
- Dizziness or lightheadedness
- Feeling tired or weak
- Muscle pain
- Nausea and vomiting
- Irregular or fast heartbeat
If you have hepatitis B virus and start taking Genvoya, your hepatitis B may get worse.
There are many medications that can interact with Genvoya and cause serious issues. It’s important to tell your healthcare provider about any medications you are currently taking, have recently taken, or plan to start taking. Avoid taking antacids, sucralfate, multivitamins, or other products containing calcium, magnesium, aluminum, iron, or zinc 2 hours before or after taking Genvoya.
Rarely, Genvoya may also cause new or worsening kidney issues. This includes an increased risk of kidney failure. Your healthcare provider will need to monitor your kidney function before you start and while taking Genvoya.
Before starting Genvoya, tell your doctor if you:
- Have or previously had hepatitis B virus
- Have a history of liver or kidney problems
- Are pregnant or planning to become pregnant
- Are breastfeeding or planning to breastfeed
- Are taking any over-the-counter vitamins, supplements, medicines, or herbal remedies
- Are on any other medications or are about to start any other medications, including hormonal birth control or medications for hepatitis viruses
Genvoya may cause a condition called IRIS (immune reconstitution inflammatory syndrome). IRIS occurs when an individual’s immune system gets stronger after being weak and responds aggressively to previously hidden infections. This heightened response may make the person fighting the infection feel worse. Alert your healthcare provider immediately if you begin to have new symptoms after taking Genvoya. These are not all the possible side effects of Genvoya. Patients should talk to their doctor about what to expect with treatment with Genvoya.