Bictegravir-Emtricitabine-Tenofovir

• HIV-1 Infection
• Antiretroviral Therapy
• HIV Treatment
• Single-Tablet HIV Regimen

Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is a fixed-dose combination antiretroviral medication used for the treatment of HIV-1 infection. This single-tablet regimen combines an integrase strand transfer inhibitor (INSTI) with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) to provide a complete HIV treatment regimen.

Mechanism of Action

This combination contains three antiretroviral agents with distinct mechanisms. Bictegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of HIV DNA integration, which is essential for the HIV replication cycle. Emtricitabine is a nucleoside analog of cytidine that is phosphorylated to its active metabolite, emtricitabine triphosphate, which competes with deoxycytidine triphosphate and inhibits HIV reverse transcriptase by terminating the DNA chain. Tenofovir alafenamide is a prodrug of tenofovir that is converted intracellularly to the active metabolite tenofovir diphosphate, which inhibits HIV reverse transcriptase through DNA chain termination.

Available Formulations

The medication is available as fixed-dose combination tablets containing bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg. A lower strength tablet (bictegravir 30 mg/emtricitabine 120 mg/tenofovir alafenamide 15 mg) is available for pediatric patients weighing 14 to less than 25 kg. The tablet can be taken with or without food.

Medical Uses

BIC/FTC/TAF is FDA-approved for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 14 kg who have no antiretroviral treatment history or who are virologically suppressed on a stable antiretroviral regimen with no history of treatment failure and no known resistance to the individual components. Clinical trials demonstrated non-inferiority or superiority compared to other guideline-recommended regimens, with high rates of viral suppression.

Dosing Guidelines

For adults and pediatric patients weighing at least 25 kg, the dose is one tablet (50/200/25 mg) taken orally once daily with or without food. For patients weighing 14 to less than 25 kg, one low-dose tablet (30/120/15 mg) once daily is recommended. If taken with rifabutin, an additional 50 mg dose of bictegravir should be taken with the combination tablet. The medication should not be used with other antiretroviral drugs unless treating hepatitis B coinfection.

Important Safety Information

Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HIV and HBV who discontinued this medication. All patients should be tested for HBV before initiating therapy, and those with HBV coinfection should be monitored closely if therapy is discontinued. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with nucleoside analogs. Immune reconstitution syndrome may occur during initial HIV treatment. New onset or worsening renal impairment has been observed.

Drug Interactions

Bictegravir is a substrate of CYP3A and UGT1A1. Strong CYP3A inducers (rifampin, St. John's Wort) significantly decrease bictegravir levels and are contraindicated. Dofetilide is contraindicated due to potential increased dofetilide concentrations. Polyvalent cation-containing products (antacids, iron supplements) should be taken at least 2 hours before or after BIC/FTC/TAF. Metformin dose should be limited when taken with this medication. The medication interacts with other antiretrovirals and should not be coadministered unless managing HBV coinfection.

Special Populations

There are insufficient human data on use during pregnancy. The Antiretroviral Pregnancy Registry monitors outcomes in pregnant women. Emtricitabine and tenofovir are excreted in breast milk; HIV-infected mothers should not breastfeed due to the risk of HIV transmission. Safety and efficacy have been established in pediatric patients weighing at least 14 kg. No dose adjustment is needed for elderly patients. The medication is not recommended for patients with CrCl below 30 mL/min or on dialysis. No dose adjustment is needed for hepatic impairment.