Indications
Bictegravir, in combination with tenofovir alafenamide and emtricitabine, is indicated for the treatment of human immunodeficiency virus-1 (HIV-1) infection. This regimen is approved for patients weighing at least 14 kg. In the United States, it is suitable for treatment-naive individuals or for those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen without any known or suspected resistance substitutions related to bictegravir or tenofovir. In Europe, it is also approved for patients aged 2 years and older who exhibit viral resistance to the integrase inhibitor class, emtricitabine, or tenofovir.
Pharmacodynamics
Bictegravir functions as an HIV-1 integrase strand transfer inhibitor (INSTI). It works by inhibiting the integration of viral DNA into the host cell genome, thereby hampering the replication of HIV-1. This mechanism of action allows for effective viral suppression when taken once daily without the need for multiple dosing schedules.
Absorption
After administration, Bictegravir is rapidly absorbed in the body, achieving peak concentrations within approximately 2 to 4 hours (Tmax).
Metabolism
The metabolism of Bictegravir occurs primarily in the liver and kidneys, involving the enzymes CYP3A4 and UGT1A. In clinical studies, the median half-life of Bictegravir ranged from 15.9 to 20.9 hours, depending on the dosage administered. It is recommended that Bictegravir should not be prescribed to patients with a renal creatinine clearance of less than 30 mL/min or those with significant hepatic impairment.
Mechanism of Action
Bictegravir functions as a potent inhibitor of the HIV-1 integrase enzyme, thereby blocking the strand transfer of viral DNA into the human genome and preventing the replication and propagation of the HIV-1 virus. In vitro studies indicate that bictegravir exhibits strong antiviral activity against HIV-2 and various HIV-1 subtypes. It has shown synergistic effects when administered with other antiretrovirals, such as tenofovir alafenamide (TAF), emtricitabine (FTC), and darunavir (DRV). Biktarvy, the first medication approved in the USA containing these three components, combines their unique mechanisms of action to combat HIV infection effectively.
