Biktarvy - Drug Monograph

Of course. Here is a comprehensive, evidence-based drug monograph for Biktarvy, formatted as a complete blog post.

Introduction

Biktarvy is a modern, fixed-dose combination antiretroviral medication used for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection. It is classified as a complete, single-tablet regimen (STR), meaning it contains all the necessary components for a full HIV treatment regimen in one pill taken once daily. Since its approval by the FDA in 2018, Biktarvy has become a cornerstone of HIV therapy due to its high efficacy, favorable safety profile, and high barrier to resistance.

Mechanism of Action

Biktarvy combines three antiretroviral agents with distinct mechanisms of action that target different stages of the HIV replication cycle:

1. Bictegravir (50 mg): An integrase strand transfer inhibitor (INSTI). It inhibits the HIV integrase enzyme, which is responsible for inserting (strand transfer) the viral DNA into the host cell's DNA. This step is essential for the creation of the provirus and subsequent viral replication. 2. Emtricitabine (200 mg): A nucleoside reverse transcriptase inhibitor (NRTI). It is a cytosine analog that is phosphorylated intracellularly to its active form, emtricitabine 5'-triphosphate. This active form competes with the natural substrate deoxycytidine 5'-triphosphate and incorporates into nascent viral DNA, leading to chain termination and halting DNA synthesis. 3. Tenofovir Alafenamide (25 mg): A nucleotide reverse transcriptase inhibitor (NtRTI). It is a prodrug of tenofovir that is preferentially metabolized intracellularly by cathepsin A to tenofovir, which is then phosphorylated to the active metabolite tenofovir diphosphate. Tenofovir diphosphate inhibits HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5'-triphosphate and, after incorporation into DNA, causes chain termination.

The synergistic action of these three components potently suppresses viral replication, reducing the viral load in the blood and allowing for immune reconstitution.

Indications

Biktarvy is indicated for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 25 kg who are either: * Antiretroviral-naïve: Starting HIV treatment for the first time. * Virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for at least 3 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy.

It is not indicated for use as pre-exposure prophylaxis (PrEP).

Dosage and Administration

* Standard Adult Dosage: One tablet taken orally once daily, with or without food. * Pediatric Dosage: For patients weighing ≥25 kg, the recommended dosage is one tablet taken orally once daily, with or without food. * Missed Dose: If a dose is missed, the patient should take it as soon as they remember, unless it is closer to the time of the next dose. They should not double the next dose. * Renal Impairment: * Not recommended in patients with estimated creatinine clearance (CrCl) <30 mL/min. * Not recommended in patients who are receiving dialysis. * Hepatic Impairment: No dosage adjustment is required in patients with mild to moderate hepatic impairment (Child-Pugh Class A or B). Not recommended in patients with severe hepatic impairment (Child-Pugh Class C).

Pharmacokinetics

* Absorption: The bioavailability of bictegravir, emtricitabine, and tenofovir alafenamide is unaffected by food. The median time to maximum plasma concentration (Tmax) is 2.0 hours for bictegravir, 2.0 hours for emtricitabine, and 1.0 hour for tenofovir alafenamide. * Distribution: Bictegravir is >99% protein-bound. Emtricitabine and tenofovir have low protein binding (<4% and ~0.7%, respectively). * Metabolism: Bictegravir is metabolized primarily via CYP3A4 and UGT1A1. Emtricitabine is minimally metabolized. Tenofovir alafenamide is metabolized intracellularly to tenofovir. * Elimination: The mean terminal plasma half-life is ~18 hours for bictegravir, ~10 hours for emtricitabine, and ~0.5 hours for tenofovir alafenamide. Bictegravir and emtricitabine are excreted via multiple pathways (feces and urine). Tenofovir is primarily excreted renally by glomerular filtration and active tubular secretion.

Contraindications

Biktarvy is contraindicated: * In patients with a previous hypersensitivity reaction to any of its components. * When co-administered with rifampin, a potent CYP3A inducer, as it significantly decreases bictegravir plasma concentrations, leading to potential loss of virologic response and development of resistance.

Warnings and Precautions

* Exacerbations of Hepatitis B: WARNING: Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine and/or tenofovir disoproxil fumarate (TDF). Monitor hepatic function closely in these patients for several months after stopping Biktarvy. Biktarvy is not approved for the treatment of HBV. * Drug Interactions with Bictegravir: Bictegravir is a substrate of CYP3A and UGT1A1. Co-administration with strong inducers of these enzymes (e.g., rifampin, St. John's Wort) is contraindicated or not recommended, as it may decrease bictegravir levels. Co-administration with strong inhibitors of CYP3A (e.g., ketoconazole) may increase bictegravir levels, but no dosage adjustment is needed. * Renal Impairment: Biktarvy contains tenofovir alafenamide, which has a more favorable renal profile than tenofovir disoproxil fumarate (TDF). However, it is not recommended in patients with CrCl <30 mL/min due to a lack of data. Assess CrCl, urine glucose, and urine protein before initiating and during therapy. * Lactic Acidosis/Severe Hepatomegaly with Steatosis: Rare but serious events have been reported with nucleoside analogs. Discontinue use if clinical or laboratory findings suggest this diagnosis.

Drug Interactions

Biktarvy has several clinically significant drug interactions, primarily due to bictegravir's metabolism.

| Interacting Drug Class | Example Drugs | Effect & Recommendation | | :--- | :--- | :--- | | Strong CYP3A Inducers | Rifampin, Rifapentine, St. John's Wort, Carbamazepine, Phenytoin | Contraindicated. Significantly decreases bictegravir plasma concentration. | | Polyvalent Cation Containing Antacids or Laxatives | Aluminum/Magnesium hydroxide, Calcium carbonate, Succalfate | Decreases bictegravir absorption. Administer Biktarvy 2 hours before or 6 hours after these products. | | Other Antiretrovirals | Didanosine (buffered formulation) | Separate administration by 2 hours. | | Nephrotoxic Drugs | Acyclovir, Cidofovir, Ganciclovir, Vancomycin, Aminoglycosides, High-dose NSAIDs | May compete for active tubular secretion or increase risk of renal impairment. Monitor renal function. |

Adverse Effects

* Common Adverse Reactions (≥5%, all grades): In clinical trials, the most common adverse reactions were diarrhea (6%), nausea (5%), and headache (5%). * Serious Adverse Reactions: Include the warnings listed above (hepatitis B exacerbation, lactic acidosis). Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. * Laboratory Abnormalities: * Increases in serum creatinine (due to inhibition of tubular secretion of creatinine by tenofovir, not indicative of renal injury) * Increases in total bilirubin (associated with UGT1A1 inhibition by bictegravir, not indicative of hepatic injury)

Monitoring Parameters

* Virologic Efficacy: HIV-1 RNA viral load at baseline and regularly until suppressed, then every 3-6 months. * Immunologic Efficacy: CD4+ T-cell count at baseline and regularly. * Renal Function: Serum creatinine, estimated CrCl, urinalysis (for glucose and protein) at baseline and during therapy. * Hepatitis B & C Coinfection: Test for HBV and HCV at baseline. In HBV coinfected patients, monitor hepatic function (ALT, AST, bilirubin) closely, especially if discontinuing Biktarvy. * Adherence: Regular assessment of adherence to therapy is critical to ensure virologic suppression and prevent resistance.

Patient Education

* Adherence is Critical: Emphasize the importance of taking Biktarvy exactly as prescribed, every day, to maintain viral suppression, improve health, and reduce the risk of developing drug resistance. * Do Not Stop: Instruct patients not to run out of medication or stop taking Biktarvy without first talking to their healthcare provider, especially if they have hepatitis B. * Timing of Dose: Biktarvy can be taken with or without food. If taking antacids, take Biktarvy 2 hours before or 6 hours after. * Side Effects: Inform patients of common side effects like diarrhea, nausea, and headache, which are often transient. Instruct them to report any severe symptoms, especially signs of new infection or persistent nausea/vomiting/abdominal pain. * Drug Interactions: Advise patients to inform all healthcare providers of all medications they are taking, including over-the-counter drugs, herbal supplements (especially St. John's Wort), and vitamins. * Pregnancy Registry: Inform patients that there is an Antiretroviral Pregnancy Registry to monitor outcomes in individuals exposed to Biktarvy during pregnancy.

References

1. Gilead Sciences, Inc. (2023). Biktarvy® (bictegravir, emtricitabine, and tenofovir alafenamide) tablets, for oral use [Prescribing Information]. Foster City, CA. 2. Sax, P. E., Pozniak, A., Montes, M. L., et al. (2017). Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir plus emtricitabine and tenofovir alafenamide in initial treatment for HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. The Lancet HIV, 7(6), e389-e400. 3. Gallant, J., Lazzarin, A., Mills, A., et al. (2017). Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. The Lancet, 390(10107), 2063-2072. 4. Panel on Antiretroviral Guidelines for Adults and Adolescents. (2023). Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. Available at: [https://clinicalinfo.hiv.gov/en/guidelines](https://clinicalinfo.hiv.gov/en/guidelines) 5. Post, F. A., Tebas, P., & Feinberg, J. (2021). Understanding the role of Biktarvy® in the management of HIV-1 infection: a review of the evidence. HIV Research & Clinical Practice, 22(1), 1-13.