Progress in HIV treatment involves offering options that can be tailored to the unmet needs, and preferences of people with HIV. As HIV care increasingly spans decades, the continuous development of novel therapeutic agents remains essential to expanding treatment options and supporting the evolving journey of people living with HIV.
This video explores the synergistic mechanism of action of BIXLENVO (bictegravir/lenacapavir), a novel combination therapy designed to target multiple stages of the HIV-1 lifecycle. BIXLENVO offers a novel option that is built on the well-studied and established clinical profile of bictegravir and the breakthrough science of lenacapavir, a first-in-class HIV-1 capsid inhibitor.
HIV infects immune cells through a multistep process and is critically dependent on the function of the viral capsid. Following HIV attachment and fusion to the host cell, the viral capsid core, a protein shell that contains and protects the viral RNA and all the enzymes required for HIV replication, is released into the cytoplasm, where the capsid-enclosed reverse transcriptase initiates transcription of viral RNA into viral DNA.
The capsid is transported inside the nucleus where it disassembles, releasing the viral enzymes and fully transcribed viral DNA. The viral integrase enzyme mediates the incorporation of the viral genome into the host cell DNA, resulting in an integrated genome that enables the synthesis of new HIV polyproteins, including capsid precursor polyproteins, that assemble on the host cell membrane and bud off in an immature, noninfectious state.
Cleavage of precursor polyproteins by the viral protease triggers maturation and the formation of the capsid core around the viral genome and enzymes producing new, infectious HIV virions.
Let’s learn about the mechanism of action of BIXLENVO, a novel combination of an integrase strand transfer inhibitor and a capsid inhibitor.
Indication:
BIXLENVO is indicated as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no known or suspected resistance to the individual components of BIXLENVO.
Important safety information.
Contraindications
Coadministration:
Concomitant administration of BIC-LEN is contraindicated with dofetilide and strong CYP3A inducers.
Please see additional important Safety information for BIXLENVO later in the video and full prescribing information for BIXLENVO available at bixlenvoHCP.com.
BIXLENVO components, bictegravir or BIC and lenacapavir or LEN, have been formulated as an intentional combination that synergizes to target HIV-1 replication at multiple stages.
BIC is a second-generation integrase strand transfer inhibitor or INSTI. BIC binds to the HIV-1 integrase enzyme inside the host cell nucleus, disrupting the strand transfer of HIV-1 DNA into the host DNA, preventing genome integration and halting HIV-1 replication. BIC demonstrated no cross-resistance in-vitro to mutants associated with resistance to NRTIs, NNRTIs, or PIs.
LEN is a first-in-class HIV-1 capsid inhibitor that targets multiple stages of the HIV-1 lifecycle. Directly binding to the interface between capsid protein subunits, LEN disrupts capsid-mediated nuclear uptake of HIV-1 proviral DNA, inhibits virus assembly and release from the host cell by binding to and destabilizing the capsid precursor proteins that assemble at the plasma membrane, and disrupts capsid core assembly during maturation, targeting multiple stages of the HIV-1 lifecycle. LEN targets the HIV-1 capsid, a distinct protein from those targeted by other antiretroviral classes. LEN demonstrated no overlapping resistance in vitro to any currently approved antiretroviral therapy.
Paired with purpose, BIXLENVO is a single-tablet regimen with a unique mechanism of action to treat HIV-1. Through inhibition of the HIV-1 integrase enzyme and capsid disruption at multiple stages of the HIV-1 lifecycle, BIXLENVO offers a novel, once-daily, oral combination treatment that pairs the well-established clinical profile of bictegravir with lenacapavir, a first-in-class HIV-1 capsid inhibitor. With its synergistic mechanism of action, BIXLENVO offers a novel treatment option for people living with HIV.
IMPORTANT SAFETY INFORMATION
Contraindications
Coadministration: Concomitant administration of BIXLENVO is contraindicated with dofetilide and strong CYP3A inducers.
Warnings and precautions
See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during BIXLENVO therapy and monitor for adverse reactions.
Adverse reactions
Most common adverse reactions (≥2%) reported in clinical trials were headache (4%), nausea (3%), and diarrhea (2%).
Drug interactions
Prescribing Information: Consult the full Prescribing Information for BIXLENVO for more information on contraindications, warnings, and potentially significant drug interactions, including clinical comments.
Enzymes/transporters: Drugs that are both a strong inducer of CYP3A and induce UGT1A1 can substantially decrease the concentration of components of BIXLENVO. Drugs that are strong or moderate inducers of CYP3A may significantly decrease the concentrations of components of BIXLENVO. Drugs that are both a strong CYP3A inhibitor and a UGT1A1 inhibitor, or combined P-gp, UGT1A1, and strong CYP3A inhibitors can significantly increase concentrations of components of BIXLENVO.
Dosage and administration
Dosage: Two-day initiation regimen of BIXLENVO 1 tablet plus SUNLENCA 2 tablets taken orally daily, followed by a maintenance regimen of BIXLENVO 1 tablet orally once daily. Tablets may be taken with or without food.
Day 1: BIXLENVO 1 tablet of 75 mg/50 mg orally AND SUNLENCA 2 tablets of 300 mg orally (600 mg dose)
Day 2: BIXLENVO 1 tablet of 75 mg/50 mg orally AND SUNLENCA 2 tablets of 300 mg orally (600 mg dose)
Day 3 and once daily thereafter: BIXLENVO 1 tablet of 75 mg/50 mg orally once daily
Missed dose: If the initiation doses of BIXLENVO or SUNLENCA are missed, patients should take them as soon as possible. Patients should not take both Day 1 and Day 2 doses of SUNLENCA on the same day. Patients should take missed maintenance doses as soon as possible. If more than 7 days have elapsed since the last maintenance dose, restart initiation dosage regimen from Day 1, if clinically appropriate to continue treatment.
Pregnancy and lactation
Pregnancy: Lower exposures of bictegravir were observed in clinical studies with a bictegravir-containing regimen; therefore, viral load should be monitored closely in pregnant individuals. An Antiretroviral Pregnancy Registry (APR) has been established.
Lactation: Individuals with HIV-1 should be informed of the potential risks of breastfeeding.
INDICATION:
BIXLENVO is indicated as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no known or suspected resistance to the individual components of BIXLENVO.
Please see full Prescribing Information for BIXLENVO available at BixlenvoHCP.com.
For more information about BIXLENVO, please visit BixlenvoHCP.com. Thank you.
