Reviewed by: HU Medical Review Board | Last reviewed: 5/31/22 | Last updated: October 2022
Symtuza is a combination medication that contains darunavir, cobicistat, emtricitabine and tenofovir alafenamide. It is used as a standalone antiretroviral therapy (ART) regimen for HIV-1 in patients who have never taken HIV medications before; it is also approved pediatric patients over 40kg.1,2
Patients who have previously taken HIV medications can still take Symtuza, as long as they have no drug resistance mutations to darunavir or tenofovir alafenamide (two of the ingredients in Symtuza) 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 Symtuza?
The main ingredients in Symtuza are darunavir, cobicistat, emtricitabine and tenofovir alafenamide. Darunavir is a protease inhibitor (PI). Cobicistat is a CYP3A inhibitor, also referred to as a pharmacokinetic enhancer. Emtricitabine and tenofovir alafenamide are nucleoside reverse transcriptase inhibitors (NRTIs).
How does Symtuza work for HIV?
Symtuza is a combination of two NRTI medications, a protease 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.
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 protease inhibitors work?
If the virus is able to make it through the reverse transcription and get inserted into host DNA, it can be made into a type of genetic material called messenger RNA (mRNA). mRNA is used to create proteins, including the enzymes HIV virions carry around with them in order to live. During the process of converting mRNA into these proteins, the virus uses its protease enzyme. The protease enzyme cuts the mRNA into sections that will eventually be turned into the different proteins required for new, mature viruses to form.
PIs inhibit this protease enzyme and prevent it from cutting the mRNA into its different parts. Without this cutting, or cleavage, of the mRNA, the final protein products aren’t able to be made and a mature virus cannot be formed and released into the blood to infect 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 darunavir, 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 effects of Symtuza include, but are not limited to:
- Abdominal discomfort
Things to be aware of
As with any medication, there are several very rare but serious risks that need to be considered before taking Symtuza. 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 Symtuza include liver issues, skin reactions, 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 a serious skin reaction include the following:
- Skin blisters or peeling
- Mouth sores
- Swelling of the lips, mouth, face, or throat
- Redness or swelling of the eyes
- Muscles or joint aches
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
These are not all the possible side effects of Symtuza. Patients should talk to their doctor about what to expect with treatment with Symtuza.
If you have hepatitis B virus and start taking Symtuza, your hepatitis B may get worse. There are many medications that can interact with Symtuza 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.
Symtuza 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 Symtuza. New or worsening diabetes and high blood sugar may also occur while taking Symtuza. Individuals with hemophilia who take Symtuza may experience increased bleeding.
Before starting Symtuza, tell your doctor if you:
- Have or previously had hepatitis B virus
- Have or previously had hepatitis C virus
- Have a history of liver or kidney problems
- Have diabetes
- Have hemophilia
- Are allergic to drugs called sulfa drugs (sulfonamide-containing medications)
- 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
Symtuza 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 Symtuza. Symtuza may also cause changes in body fat, especially around the breast, trunk, upper back, and neck regions.