Biktarvy

Summary

Biktarvy contains three medicines—bictegravir, tenofovir alafenamide (TAF) and FTC. Bictegravir belongs to the class of drugs called integrase inhibitors. TAF and FTC belong to the class of drugs called nucleoside reverse transcriptase inhibitors (“nukes”). Biktarvy is taken at a dose of one pill once daily with or without food. Overall, Biktarvy was well-tolerated in clinical trials. General side effects were uncommon and included headache and diarrhea; these were usually mild and temporary.

What is Biktarvy?

Biktarvy contains three medicines—bictegravir, TAF and FTC. Bictegravir belongs to the class of drugs called integrase inhibitors. TAF and FTC belong to the class of drugs called nucleoside reverse transcriptase inhibitors (“nukes”). Biktarvy was approved in Canada in 2018. The combination of TAF and FTC was approved in 2016. What is new is that Biktarvy combines TAF, FTC and bictegravir in one pill.

How does Biktarvy work?

The drugs in Biktarvy work by interfering with enzymes needed by HIV called integrase and reverse transcriptase. Using Biktarvy greatly reduces HIV’s ability to infect cells and make copies of itself.

How do people with HIV use Biktarvy?

Biktarvy is meant for use by adults. Gilead, the manufacturer of Biktarvy recommends that the following be done prior to initiating treatment with Biktarvy:

• testing for hepatitis B virus infection
• assessing levels of creatinine in the blood, as well as levels of glucose and protein in the urine; assessing estimated glomerular filtration rate (eGFR). Also, in patients with chronic kidney disease, Gilead advises to assess the level of phosphorus in the blood.

For more information about HIV treatment, see CATIE’s Your Guide to HIV Treatment.

For many people with HIV, the use of ART (HIV treatment or antiretroviral therapy) has increased their CD4+ cell counts and decreased the amount of HIV in their blood (viral load). These beneficial effects help to greatly reduce the risk of developing a life-threatening infection or an AIDS-related cancer. Neither Biktarvy nor any other treatment regimen (ART) is a cure for HIV. It is therefore important that you see your doctor for checkups and lab tests on a regular basis.

Evidence shows that HIV-positive people who are on ART, engaged in care, and have an ongoing undetectable viral load are substantially less likely to transmit HIV to others, be it through sex, when sharing equipment to use drugs or during pregnancy and birth. In fact, the evidence for sexual transmission shows that people on ART who maintain an undetectable viral load do not pass HIV to their sexual partners. For further information see the CATIE fact sheet HIV treatment and an undetectable viral load to prevent HIV transmission. However, it is still a good idea to use condoms because they can reduce your risk for getting and passing on other sexually transmitted infections.

Warnings

Pregnancy

Biktarvy (and bictegravir inside Biktarvy) are new and there is no information about the safety of Biktarvy in pregnancy. Gilead recommends “Biktarvy should not be used during pregnancy unless the potential benefits outweigh the potential risks to the fetus.”

If you are taking Biktarvy and are pregnant or want to have a baby, speak to your doctor right away.

Liver health

Caution with Biktarvy cessation

TAF and FTC (both of which are inside Biktarvy) have activity against hepatitis B virus (HBV). In people who are co-infected with HIV and HBV, if you change your regimen from Biktarvy to something else that does not have TAF or FTC, you can develop worsening HBV infection. This flaring up of HBV may be symptom-free or it may be associated with a wide range of symptoms, including the following:

• yellowing of the skin and the whites of the eye
• loss of appetite
• feeling tired
• muscle, joint, or stomach pain
• upset stomach, nausea, diarrhea, or vomiting
• Blood tests may find that levels of liver enzymes are higher than normal.

Gilead recommends that if Biktarvy is discontinued and your new regimen does not contain tenofovir and/or FTC that the health and functioning of your liver “should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are co-infected with HIV and HBV.”

Liver injury or dysfunction

Gilead recommends that Biktarvy not be used in people who have severe liver injury (graded as “Child-Pugh C”). Gilead notes that no adjustment of Biktarvy is needed for people who have mild or moderate liver injury or dysfuction.

Kidney health

Another, older formulation of tenofovir (tenofovir disoproxil fumarate or TDF) has been associated with cases of kidney injury and kidney failure. However, in clinical trials of Biktarvy, such problems have not been reported. Still, Gilead recommends that Biktarvy not be used in people whose eGFR (estimated glomerular filtration rate) is 30 mL/minute or lower.

Gilead cautions that people who take Biktarvy (and other drugs containing tenofovir) and who also take medicines that can injure the kidneys (such as non-steriodal anti-inflammatory drugs) “are at increased risk” for developing kidney injury.

The following drugs and substances have the potential to weaken the health of the kidneys (this list is not exhaustive):

• antibiotics – gentamicin, amikacin, vancomycin, rifampin
• anti-cancer drugs – Cisplatin (cis-platinum), carboplatin, Avastin (bevacizumab), gemcitabine
• anti-fungal drugs – amphotericin B, pentamidine
• anti-viral drugs – foscarnet (Foscavir), cidofovir (Vistide), acyclovir, valacyclovir
• non-steroidal anti-inflammatory drugs (NSAIDs) – Aspirin (acetylsalicylic acid), celecoxib (Celebrex), diclofenac (Voltaren), ibuprofen (Advil, Motrin); indomethacin, naproxen, ketorolac (Acular),
• street drugs – cocaine, heroin

Your doctor, nurse or pharmacist may recommend the temporary use of one of these medicines because they are medically necessary. However, chronic use of some of these medicines, such as NSAIDS, may increase your risk for kidney injury.

Age

Biktarvy has not been tested in people younger than 18 years. Biktarvy has also not been tested in large numbers of people who are 65 years or older so its effectiveness and safety in these populations is not known.

Side effects

General

In clinical trials, Biktarvy was well tolerated, generally safe and effective. However, as with any treatment, there were side effects but these were uncommon and usually temporary and included the following:

• headache
• nausea
• diarrhea

Note that the HIV-positive people who are typically enrolled in pivotal clinical trials of HIV treatments, including Biktarvy, are generally young and healthy. Once a drug is approved and more widely available, it gets used by populations who are not usually in pivotal clinical trials. These people may be older and may have other health issues—such as cardiovascular disease, liver injury, kidney injury, type 2 diabetes, anxiety, depression, and substance use—that require medications or that cause symptoms. As a result, their experience of side effects may be different from those reported in pivotal clinical trials.

Uncommon symptoms

The following symptoms were uncommon in clinical trials, affecting less than 2% of Biktarvy users; it is not clear if these symptoms were caused by Biktarvy, the underlying disease process or something else:

• lack of energy
• abdominal pain
• nausea
• vomiting
• muscle soreness
• decreased appetite
• feeling sleepy during the daytime

Drug interactions

Some drugs (including prescribed and over-the-counter), herbs and supplements can interfere with the absorption and/or effectiveness of Biktarvy. Such interference is called a drug interaction. Some drugs can reduce the levels of the medicines in Biktarvy in your blood. This can make Biktarvy less effective and lead to treatment failure, reducing your future treatment options. Other drugs can raise the levels of medicines in Biktarvy in your blood, resulting in enhanced side effects or new side effects. Therefore it is important to disclose to your doctor and pharmacist all the supplements, drugs, and herbs you are taking.

This factsheet is not comprehensive and only lists some of the potential and actual drug interactions with Biktarvy. Speak to your pharmacist to find out more about drug interactions with Biktarvy.

Not to be used

Gilead recommends that the following drugs should not be used by people taking Biktarvy:

• for treatment of abnormal heart rhythms – dofetilide (Tikosyn)
• anti-seizure drugs – carbamazepine, oxcarbazepine, phenobarbital and phenytointhe antibiotic – rifampin
• St. John’s Wort or extracts of this herb including hypericin and hyperforin

Acid-reducing agents, laxatives, metal supplements and buffered medicines

Gilead recommends that Biktarvy be taken two hours before or two hours after taking medicines or supplements that contain metals (calcium, iron, magnesium or aluminium). Examples of these include:

• Alka-Seltzer
• Calcium and/or magnesium liquid and tablets
• Gaviscon (tablets and syrup)
• Maalox (liquid and tablets)
• Milk of Magnesia
• Pepto-Bismol and Pepto Bismol Childen’s
• Rolaids
• Tums

As an alternative, people who take supplements or medicines with calcium, magnesium, iron or aluminum, can take them with Biktarvy together with food.

Resistance and cross-resistance

Over time, as new copies of HIV are made in the body, the virus changes its structure. These changes, called mutations, can cause HIV to resist the effects of anti-HIV drugs, which means those drugs will no longer work for you.

To reduce the risk of developing drug resistance, all anti-HIV drugs should be taken every day exactly as prescribed and directed. If doses are delayed, missed or not taken as prescribed, the level of the medicines in Biktarvy in the blood may fall too low. If this happens, the HIV in your body can become resistant to the medication. If you find you are having problems taking your medications as directed, speak to your doctor, nurse or pharmacist about this. They can find ways to help you.

When HIV becomes resistant to one drug in a class, it sometimes becomes resistant to other drugs in that class. This is called cross-resistance. Feel free to talk with your doctor about your current and future treatment options. To help you decide what these future options might be, at some point your doctor can have a small sample of your blood analyzed to test for resistance.

Dosage

Biktarvy is supplied as purplish brown tablets. Each tablet contains 50 mg of bictegravir, 25 mg of TAF and 200 mg of FTC. Biktarvy is taken once daily with or without food.

• If you forget to take a dose, Gilead recommends the following:
• If you miss a dose of Biktarvy and you notice within 18 hours of the time you usually take Biktarvy, take the tablet as soon as you can. Then take the next dose as usual.
• If you miss a dose of Biktarvy and you notice after 18 hours, wait and take the next dose at your usual time.
• Do NOT take a double dose (two doses close together).

Availability

Biktarvy is licensed in Canada for the treatment of HIV infection in adults. Your doctor or pharmacist can tell you more about the availability and coverage of Biktarvy in your region. CATIE’s online module Federal, Provincial and Territorial Drug Access Programs also contains information about Canadian drug coverage.

References

1. Gilead Sciences Canada. Biktarvy. Product Monograph. 10 July, 2018.
2. Waikar SS and Bonventre JV. Chapter 334. Acute kidney injury. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill.