General Information

Biktarvy is a once daily single tablet containing a three-drug combination of bictegravir (BIC), a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI), and emtricitabine (FTC) and tenofovir alafenamide (TAF), both HIV-1 nucleoside analog reverse transcriptase inhibitors (NRTIs).

Biktarvy is specifically indicated as a complete regimen for the treatment of HIV-1 infection in adults who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 c/mL) on a stable antiretroviral regimen for at least three months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy.

Biktarvy is supplied as a tablet for oral administration. The recommended dose is one tablet once daily with or without food. 

Mechanism of Action

Bictegravir: BIC inhibits the strand transfer activity of HIV-1 integrase (integrase strand transfer inhibitor; INSTI), an HIV-1 encoded enzyme that is required for viral replication. Inhibition of integrase prevents the integration of linear HIV-1 DNA into host genomic DNA, blocking the formation of the HIV-1 provirus and propagation of the virus.

Emtricitabine: FTC, a synthetic nucleoside analog of cytidine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of the HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA which results in chain termination.

Tenofovir Alafenamide: TAF is a phosphonamidate prodrug of tenofovir (2′-deoxyadenosine monophosphate analog). Plasma exposure to TAF allows for permeation into cells and then TAF is intracellularly converted to tenofovir through hydrolysis by cathepsin A. Tenofovir is subsequently phosphorylated by cellular kinases to the active metabolite tenofovir diphosphate. Tenofovir diphosphate inhibits HIV-1 replication through incorporation into viral DNA by the HIV reverse transcriptase, which results in DNA chain-termination.

Side Effects

Adverse events associated with the use of Biktarvy may include, but are not limited to, the following:

• diarrhea
• nausea
• headache

The Biktarvy drug label comes with the following Black Box Warning: Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of Biktarvy. Closely monitor hepatic function in these patients. If appropriate, anti-hepatitis B therapy may be warranted.

Clinical Trial Results

The FDA approval of Biktarvy was based on four Phase III studies: Studies 1489 and 1490 in treatment-naïve HIV-1 infected adults, and Studies 1844 and 1878 in virologically suppressed adults. 

In Study 1489: a total of 629 treatment-naïve adults with HIV were randomized 1:1 to receive Biktarvy or abacavir/dolutegravir/lamivudine (600/50/300mg) (ABC/DTG/3TC). At Week 48, 92.4% (n=290/314) of patients taking Biktarvy and 93% of patients taking ABC/DTG/3TC achieved the primary endpoint of HIV-1 RNA <50 c/mL. In Study 1490, a total of 645 treatment-naïve adults with HIV were randomized 1:1 to receive Biktarvy or DTG+FTC/TAF. At Week 48, 89.4% n=286/320) of patients taking Biktarvy and 92.9% (n=302/325) of patients taking DTG+FTC/TAF achieved the primary endpoint of HIV-1 RNA <50 c/mL.

In Study 1878, a total of 577 virologically suppressed (HIV-1 RNA <50 c/mL) adults with HIV taking regimens of a boosted protease inhibitor (bPI; atazanavir or darunavir) plus a dual-NRTI backbone (ABC/3TC or FTC/tenofovir disoproxil fumarate) were randomized 1:1 to continue their bPI regimen or to switch to open-label coformulated Biktarvy once daily. At the primary endpoint of Week 48, switching to Biktarvy was non-inferior to continuing on a bPI regimen with 1.7 percent of patients in each group having HIV-1 RNA ≥50 c/mL; the proportion of patients with HIV-1 RNA <50 c/mL was 92.1% in the Biktarvy arm and 88.9% in the bPI arm, according to FDA snapshot algorithm.