Bictegravir: A Comprehensive Monograph on a Second-Generation Integrase Strand Transfer Inhibitor

Executive Summary

Bictegravir is a potent, second-generation integrase strand transfer inhibitor (INSTI) developed by Gilead Sciences for the treatment of Human Immunodeficiency Virus Type 1 (HIV-1) infection. It represents a significant advancement in antiretroviral therapy, characterized by high efficacy, a high genetic barrier to resistance, and a favorable safety profile. Bictegravir is not available as a standalone agent; it is exclusively formulated as a component of Biktarvy®, a once-daily, single-tablet regimen (STR) that also contains the nucleoside reverse transcriptase inhibitors (NRTIs) emtricitabine (FTC) and tenofovir alafenamide (TAF). This combination provides a complete therapeutic regimen in a single pill.

The molecular mechanism of Bictegravir involves the specific inhibition of the HIV-1 integrase enzyme, a crucial catalyst in the viral replication cycle. By binding to the active site of the integrase-viral DNA complex, Bictegravir blocks the strand transfer step, thereby preventing the integration of the viral genome into the host cell's DNA. This action is highly potent, with in-vitro studies demonstrating nanomolar efficacy against wild-type HIV-1 and, critically, retained activity against many viral strains resistant to first-generation INSTIs.

The pharmacokinetic profile of Bictegravir is well-suited for a once-daily, unboosted regimen. It possesses a long elimination half-life of approximately 17-18 hours and is metabolized through dual pathways—cytochrome P450 3A4 (CYP3A4) and UDP-glucuronosyltransferase 1A1 (UGT1A1)—which provides metabolic redundancy and mitigates the risk of certain drug-drug interactions. Its absorption is minimally affected by food, enhancing patient convenience.