Bictegravir, a novel integrase inhibitor for the treatment of HIV infection

Bictegravir (BIC), a second-generation integrase strand transfer inhibitor (INSTI) approved for HIV treatment in fixed-dose combination with emtricitabine and tenofovir alafenamide, has potent antiviral activity in vitro to wild-type virus and strains with resistance to first-generation INSTIs. As part of combination therapy, BIC's virologic suppression rates in clinical trials are comparable to those of first-line combination antiretroviral drug regimens. BIC has demonstrated a high genetic barrier to resistance development in vitro, can be administered with or without food, and has a bioavailability of > 70%. A median plasma half-life of 18 hours allows once-daily dosing. Clearance is primarily hepatic through cytochrome P450 3A4 (CYP3A4) oxidation and UDP-glucuronosyltransferase 1A1 (UGT1A1) glucuronidation. Thus, potent inducers of UGT1A1 and CYP3A4 (e.g., rifamycins/anticonvulsants) should be avoided due to significantly decreased BIC serum exposure. Chelation with polyvalent cations can decrease absorption; otherwise, drug-drug interactions are few. BIC is well tolerated; diarrhea, nausea and headache are the main adverse effects associated with its use.