Bictegravir/emtricitabine/tenofovir alafenamide

Bictegravir/emtricitabine/tenofovir alafenamide, sold under the brand name Biktarvy, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It contains 50 mg bictegravir, 200 mg emtricitabine, and 25 mg tenofovir alafenamide.[3] It was approved for use in the United States in February 2018,[4][5] and for use in the European Union in June 2018.[6]

Bictegravir/emtricitabine/tenofovir alafenamide
Combination of
Bictegravirintegrase inhibitor
Emtricitabinenucleoside reverse transcriptase inhibitor
Tenofovir alafenamidenucleotide reverse transcriptase inhibitor
Clinical data
Trade namesBiktarvy
AHFS/Drugs.comMonograph
MedlinePlusa618012
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only) [2]
  • US: ℞-only [3]
  • EU: Rx-only
  • In general: ℞ (Prescription only)
Identifiers
KEGG

Combination therapy

Bictegravir/emtricitabine/tenofovir alafenamide is an example of a combination drug that can be taken as a complete regimen for treatment of the human immunodeficiency virus.[3]

Combination therapy for HIV, often called highly active antiretroviral therapy (HAART), is composed of two or more types of antiretroviral drugs. Combination therapy decreases the likelihood that drug resistance will occur, because it is unlikely that the HIV-1 strains will be able to mutate enough to become resistant to all drugs being used in the combination. Combination therapy increases the length of lives of patients with HIV-1, and can greatly reduce the possibility for transmission of the virus.[7]

Components
2D chemical structure of bictegravir

Bictegravir (BIC) is an integrase strand transfer inhibitor (INSTI). Bictegravir is different from other INSTIs because it contains a bridged bicyclic ring and a distinct benzyl tail with a 2,4,6-trifluorobenzyl group. This contributes to an increase in plasma protein binding and a reduction of activation of the pregnane X receptor (PXR). These changes minimize interactions between drugs, lower clearance, and increase solubility. Bictegravir was found to be less drug resistant than other drugs in the same class.[8]

2D chemical structure of emtricitabine

Emtricitabine (FTC) is a nucleoside reverse transcriptase inhibitor (NRTI) that is a synthetic fluoro derivative of thiacytidine. Within the cell, emtricitabine becomes phosphorylated, which forms emitricitabine 5'-triphosphate within the cell. This allows for the drug to compete with the viral and host substrate and ultimately causes a termination of DNA chain elongation.[9] Underlying hepatitis B virus (HBV) can interact with emtricitabine to cause significant liver damage, but it does not have a significant detrimental effect on the liver when given to patients without HBV.[10]

2D chemical structure of tenofovir alafenamide

Tenofovir alafenamide (TAF) is a prodrug of tenofovir that functions as a nucleotide reverse transcriptase inhibitor (NRTI). Other prodrugs for tenofovir have been tested, but TAF is more efficient at refining HIV-1 therapy. It converts intracellularly to TFV diphosphate, which is a metabolite in HIV target cells.[11] Thus, TAF has higher active metabolite concentrations and lower plasma TFV than other Tenovir prodrugs.[12] TAF is metabolized primarily with the kidneys, and has a lower dosage than other prodrugs, so it is less detrimental to the renal elimination system.[11]

Medical uses

This drug regimen is intended and approved for adults with HIV-1 infection who have had no previous antiretroviral treatment or for those with less than 50 copies of HIV-1 RNA per mL. Patients with HIV-1 should not have previously had any adverse reactions or resistance to bictegravir, emtricitabine, or tenofovir alafenamide.

Side effects

This drug should not be co-administered with dofetilide or rifampin. Dofetilide when taken with bictegravir/emtricitabine/tenofovir alafenamide can cause an increase in dofetilide plasma concentrations, which can lead to death. Rifampin and bictegravir/emtricitabine/tenofovir alafenamide when taken together can decrease bictegravir plasma concentrations and cause resistance to bictegravir/emtricitabine/tenofovir alafenamide. Other HIV-1 antiretroviral drugs should not be taken with this therapy.

If kidney disease or development of renal impairment is seen, the drug should be discontinued. Discontinuation of bictegravir/emtricitabine/tenofovir alafenamide in patients with hepatitis B and HIV-1 has been shown to increase the prevalence of hepatitis B, causing liver decompensation and liver failure.

Adverse drug reactions include, but are not limited to, diarrhea, nausea, and headache.[3]

References
  1. "Bictegravir / emtricitabine / tenofovir alafenamide (Biktarvy) Use During Pregnancy". Drugs.com. 16 September 2019. Retrieved 7 March 2020.
  2. "Biktarvy 50 mg/200 mg/25 mg film-coated tablets - Summary of Product Characteristics (SmPC)". (emc). 25 August 2020. Retrieved 26 August 2020.
  3. "Biktarvy- bictegravir sodium, emtricitabine, and tenofovir alafenamide fumarate tablet". DailyMed. 8 August 2019. Retrieved 7 March 2020.
  4. "Drug Approval Package: Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide) Tablets". U.S. Food and Drug Administration (FDA). 19 March 2018. Retrieved 7 March 2020.
  5. "U.S. Food and Drug Administration Approves Gilead's Biktarvy (Bictegravir, Emtricitabine, Tenofovir Alafenamide) for Treatment of HIV-1 Infection" (Press release). Gilead. 7 February 2018.
  6. "Biktarvy EPAR". European Medicines Agency (EMA). 21 January 2020. Retrieved 7 March 2020.
  7. "FDA-Approved HIV Medicines Understanding HIV/AIDS". AIDSinfo. Retrieved 22 May 2018.
  8. Tsiang M, Jones GS, Goldsmith J, Mulato A, Hansen D, Kan E, et al. (December 2016). "Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile". Antimicrobial Agents and Chemotherapy. 60 (12): 7086–7097. doi:10.1128/AAC.01474-16. PMC 5118987. PMID 27645238.
  9. "Emtricitabine". Pubchem. U.S. National Library of Medicine. Retrieved 22 May 2018.
  10. "Emtricitabine Dosage, Side Effects". AIDSinfo. Retrieved 22 May 2018.
  11. Ray AS, Fordyce MW, Hitchcock MJ (January 2016). "Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus". Antiviral Research. 125: 63–70. doi:10.1016/j.antiviral.2015.11.009. PMID 26640223.
  12. "Tenofovir Alafenamide Information for Providers". AIDSinfo. Retrieved 22 May 2018.
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