Bictegravir

HIV-1 Treatment

Bictegravir is a prescription medication used to manage HIV-1 infection. It belongs to a class of drugs called integrase strand transfer inhibitors (INSTIs). It is not used alone; instead, it is part of a complete treatment regimen combined with other antiretroviral medicines. The medication works by preventing the virus from multiplying, which helps to decrease the amount of HIV in the body and allows the immune system to function more effectively.

Indications for Use

Healthcare providers prescribe this medication for several groups of patients, including:

• Adults and children who meet specific weight requirements (typically at least 14 kilograms).
• Individuals who have never taken HIV medications before (treatment-naïve).
• Individuals who are switching from a different stable HIV treatment regimen, provided they have a suppressed viral load and no history of treatment failure or resistance to the components of the medication.

Goals of Therapy

The primary purpose of bictegravir is to reduce the viral load to very low levels and increase the count of CD4 cells, which are vital for the immune system. While the medication helps control the infection and may reduce the risk of developing HIV-related complications, it is not a cure for HIV or AIDS. It must be taken consistently as directed to prevent the virus from becoming resistant to treatment.

Mechanism of Action

Bictegravir belongs to a group of medicines called integrase strand transfer inhibitors (INSTIs). It works by targeting a specific enzyme that the human immunodeficiency virus (HIV) needs to reproduce.

The medication works through the following process:

• Blocking the integrase enzyme: HIV uses an enzyme called integrase to insert its own genetic material into the DNA of healthy human immune cells.
• Preventing replication: By blocking this enzyme, bictegravir prevents the virus from completing its life cycle. This stops the virus from making new copies of itself.
• Reducing viral load: As the virus is unable to multiply, the total amount of HIV in the blood (known as the viral load) decreases.

By keeping the viral load low, the medication helps the immune system stay stronger and reduces the risk of HIV-related illnesses. However, bictegravir does not cure HIV; it is used as part of a long-term treatment plan to manage the condition.

Common Side Effects

The most frequently reported side effects are usually mild and may include:

• Diarrhea
• Nausea
• Headache
• Fatigue
• Trouble sleeping (insomnia) or abnormal dreams
• Dizziness

Some individuals may also experience weight gain while taking medications containing bictegravir.

Serious Side Effects

While rare, some side effects require immediate medical attention. Contact a healthcare provider right away if you experience:

• Liver problems: Symptoms include yellowing of the skin or eyes (jaundice), dark-colored urine, light-colored stools, loss of appetite, or pain in the upper right side of the stomach area.
• Kidney problems: This may include new or worsening kidney impairment. Signs can include changes in the frequency or amount of urination.
• Lactic acidosis: A dangerous buildup of acid in the blood. Symptoms include unusual muscle pain, feeling cold in the arms and legs, trouble breathing, dizziness, or a fast or irregular heartbeat.
• Immune system changes: Also called immune reconstitution syndrome, this happens when the immune system becomes more active and begins to fight infections that were previously hidden in the body.
• Severe allergic reactions: Symptoms include rash, hives, swelling of the face, lips, or tongue, and difficulty breathing.

Hepatitis B Virus Warning

Patients with both HIV-1 and hepatitis B virus (HBV) may experience a severe worsening of their hepatitis B infection if they stop taking medications containing bictegravir. Healthcare providers typically monitor liver function closely for several months in patients who discontinue this treatment. It is important not to stop the medication without consulting a medical professional.

Drug Interactions and Contraindications

Bictegravir should not be taken with certain medications, such as dofetilide or rifampin. Using these drugs together can cause dangerous heart rhythm issues or significantly reduce the effectiveness of the HIV treatment. Additionally, supplements or antacids containing magnesium, aluminum, or iron can interfere with how the body absorbs bictegravir. These products generally need to be taken at least two hours before or after bictegravir.

Kidney Function

There is a risk of developing new or worsening kidney problems while taking this medication. Healthcare providers usually perform blood and urine tests to check kidney health before starting treatment and continue to monitor these levels periodically.

Immune System Changes

Some patients may experience immune reconstitution syndrome after starting treatment. This occurs when the immune system becomes more active and begins to fight hidden or previous infections, which can lead to new symptoms or the worsening of an existing condition.

Lactic Acidosis and Liver Health

Although less common with newer formulations, some components used alongside bictegravir can cause a buildup of lactic acid in the blood (lactic acidosis) or serious liver problems (hepatomegaly with steatosis). Symptoms to watch for include unusual tiredness, persistent nausea, stomach pain, or yellowing of the skin and eyes.

Pregnancy

There is limited data on the use of bictegravir in pregnant individuals. While animal studies have not shown evidence of harm to the fetus at high doses, human clinical data is not yet sufficient to confirm safety. Decisions regarding the use of this medication during pregnancy should be made in consultation with a healthcare provider to balance the importance of maintaining viral suppression with potential risks.

A pregnancy exposure registry exists to monitor the health outcomes of individuals and their infants who are exposed to antiretroviral medications during pregnancy. Healthcare providers can provide information on how to enroll in this registry to help improve the understanding of the drug's effects.

Breastfeeding

Health experts generally recommend that individuals with HIV avoid breastfeeding to prevent the transmission of the virus to the infant through breast milk. Additionally, it is not known if bictegravir passes into human breast milk or what effects it might have on a nursing baby. In regions where safe water and infant formula are available, these are the preferred methods for feeding to ensure the infant's safety.

Available Forms

Bictegravir is not available as a standalone medication. It is only available as a component of a fixed-dose combination tablet intended for oral administration. This combination therapy includes bictegravir along with other antiretroviral drugs.

Administration

• The medication is taken by mouth as a tablet.
• Different tablet sizes are available to accommodate both adult and pediatric patients based on weight.

FDA Approval Status

Bictegravir was first approved by the U.S. Food and Drug Administration (FDA) in February 2018. It is approved for use as a component of a complete, fixed-dose combination tablet for the treatment of human immunodeficiency virus type 1 (HIV-1) infection.

Approved Indications

The medication is indicated for the treatment of HIV-1 infection in the following populations:

• Adults and pediatric patients weighing at least 14 kilograms who have no history of antiretroviral treatment.
• Adults and pediatric patients weighing at least 14 kilograms to replace their current stable antiretroviral regimen, provided they meet specific clinical criteria regarding viral suppression and have no known resistance to the individual components of the therapy.

Boxed Warning

The FDA-approved labeling for the combination product containing bictegravir includes a boxed warning regarding the risk of post-treatment acute exacerbation of hepatitis B (HBV). Patients co-infected with HIV-1 and HBV may experience severe, acute worsening of their hepatitis B condition if they stop taking this medication. Healthcare providers are advised to monitor liver function closely in these patients for several months after treatment is discontinued.

Other Regulatory Information

Bictegravir is available only by prescription. It is not a controlled substance. While it carries a boxed warning, there is no specific Risk Evaluation and Mitigation Strategy (REMS) program required beyond the standard requirement for a patient medication guide to be provided with each prescription.

FDA Approval History

The FDA approved bictegravir on February 7, 2018, as part of a three-drug fixed-dose combination tablet. It was developed as an integrase strand transfer inhibitor (INSTI) to provide a complete treatment regimen in a single pill.

Approved Indications

Bictegravir is FDA-approved for the treatment of HIV-1 infection in the following populations:

• Adults and pediatric patients weighing at least 25 kg who have no history of antiretroviral treatment.
• Adults and pediatric patients weighing at least 25 kg to replace their current antiretroviral regimen if they are virologically suppressed on a stable regimen, have no history of treatment failure, and have no known resistance to the medication's components.
• Pediatric patients weighing at least 14 kg to less than 25 kg for specific low-dose formulations.

FDA Boxed Warning

The FDA-approved labeling for the combination product containing bictegravir includes a boxed warning regarding the risk of post-treatment acute exacerbation of hepatitis B (HBV). Patients co-infected with HIV-1 and HBV may experience severe liver problems if they discontinue the medication. Healthcare providers are required to test patients for HBV infection before initiating treatment.

Regulatory Status

Bictegravir is available only by prescription. It is not approved for use as a standalone medication and must be used as part of the specific combination therapy approved by the FDA.