Bictegravir/emtricitabine/tenofovir alafenamide

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Bictegravir/emtricitabine/tenofovir alafenamide
Combination of
Bictegravirintegrase inhibitor
Emtricitabinenucleoside reverse transcriptase inhibitor
Tenofovir alafenamidenucleotide reverse transcriptase inhibitor
Clinical data
Trade namesBiktarvy
ATC code
Legal status
Legal status
Identifiers
KEGG

Bictegravir/emtricitabine/tenofovir alafenamide (brand name Biktarvy) is a fixed dose combination drug for the treatment of HIV-1 infection. It contains 50 mg bictegravir, 200 mg emtricitabine, and 25 mg tenofovir alafenamide.[1] It was approved for use in the United States in 2018.[2]

Combination therapy[edit]

Biktarvy 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.[4]

Components[edit]

2D chemical structure of bictegravir

Bictegravir 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.[5]

2D chemical structure of emtricitabine

Emtricitabine 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.[6] 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.[7]

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.[8] Thus, TAF has higher active metabolite concentrations and lower plasma TFV than other Tenovir prodrugs.[9] 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.[8]

Indications and dosage[edit]

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 the components of Biktarvy.

Biktarvy is taken as a single tablet once per day and can be taken with or without food. Patients must be tested for hepatitis B virus infection prior to prescription. Patients must also be continually tested for serum creatinine, estimated creatinine clearance, urine glucose, and urine protein levels. Patients with a creatinine clearance of less than 30 mL per minute or patients with hepatic impairment should not be prescribed this medication.

Adverse drug reactions[edit]

This drug should not be co-administered with dofetilide or rifampin. Dofetilide when taken with Biktarvy can cause an increase in dofetilide plasma concentrations, which can lead to death. Rifampin and Biktarvy when taken together can decrease bictegravir plasma concentrations and cause resistance to Biktarvy. 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 Biktarvy 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[edit]

  1. ^ "Prescribing Information for Biktarvy" (PDF). Food and Drug Administration.
  2. ^ "U.S. Food and Drug Administration Approves Gilead's Biktarvy (Bictegravir, Emtricitabine, Tenofovir Alafenamide) for Treatment of HIV-1 Infection" (Press release). Gilead. February 7, 2018.
  3. ^ a b "BIKTARVY" (PDF). Gilead.
  4. ^ "FDA-Approved HIV Medicines Understanding HIV/AIDS". AIDSinfo. Retrieved 2018-05-22.
  5. ^ Tsiang, Manuel; Jones, Gregg S.; Goldsmith, Joshua; Mulato, Andrew; Hansen, Derek; Kan, Elaine; Tsai, Luong; Bam, Rujuta A.; Stepan, George (2016-12-01). "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. ISSN 0066-4804. PMC 5118987. PMID 27645238.
  6. ^ Pubchem. "Emtricitabine". pubchem.ncbi.nlm.nih.gov. Retrieved 2018-05-22.
  7. ^ "Emtricitabine Dosage, Side Effects". AIDSinfo. Retrieved 2018-05-22.
  8. ^ a b Ray, Adrian S.; Fordyce, Marshall W.; Hitchcock, Michael J.M. (2016-01-01). "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. ISSN 0166-3542. PMID 26640223.
  9. ^ "Tenofovir Alafenamide Information for Providers". AIDSinfo. Retrieved 2018-05-22.