Pharm to Exam Table: Clinical Pharmacology/Antimicrobial Updates – Biktarvy, a new co-formulated integrase inhibitor-based treatment approved for HIV
On February 7th 2018, the Food and Drug Administration approved a new combination antiretroviral drug called Biktarvy®(1). Biktarvy® (B/F/TAF) is a single-tablet, once daily regimen containing the novel integrase strand transfer inhibitor bictegravir coformulated with emtricitabine and tenofovir alafenamide (1). Current HIV guidelines recommend integrase strand transfer inhibitor (INSTI)-based regimens as initial therapy for HIV patients due to their high potency and a favorable side effect profile. Consequently, the introduction of a new integrase inhibitor underscores the importance of integrase strand transfer inhibitors in treating HIV infections.
B/F/TAF is a small, once-daily, single tablet regimen that offers several advantages over existing antiretroviral regimens. No HLA-B*5701 testing (abacavir hypersensitivity) is required prior to initiation, no food intake requirements, and it has a lower potential for drug-drug interactions with its lack of a pharmacokinetic booster within the formulation1. A number of randomized controlled phase III trials were instrumental in assessing the efficacy and safety of B/F/TAF. Study 1489 was a randomized, non-inferiority, trial comparing B/F/TAF to dolutegravir, abacavir, and lamivudine (3). 92·4% of treatment naive subjects in the B/F/TAF arm achieved viral suppression at 48 weeks compared to 93% in the dolutegravir, abacavir, and lamivudine arm (3).
Study 1490 was a randomized, non-inferiority, phase III trial comparing B/F/TAF to dolutegravir, emtricitabine and tenofovir alafenamide. 89.4% of treatment naive subjects in the B/F/TAF arm achieved viral suppression at 48 weeks compared to 92.9% in the dolutegravir, emtricitabine and tenofovir alafenamide arm (4). Study 1878 was an open label, randomized study comparing subjects who were virologically suppressed on a boosted protease inhibitor plus a dual nucleoside inhibitor containing regimen and then switched to B/F/TAF2. 92.1% of subjects who switched to B/F/TAF were virologically suppressed after 48 weeks compared to 88.9 % in the boosted protease inhibitor arm (2).
Notably, no treatment-emergent resistance to bictegravir was identified in any of the aforementioned studies. B/F/TAF was well tolerated with nausea, vomiting and diarrhea as the most common side effects reported. Given its unique properties, potency, and tolerable safety profile, B/F/TAF provides offers another viable option as initial therapy or as an alternative antiretroviral therapy for the treatment of HIV infection.
1 Biktarvy® [package insert].Foster City, Gilead Sciences Pharmaceuticals Incorporated; 2018
2 Gilead. Safety and Efficacy of Switching From Regimens Consisting of Boosted Atazanavir or Darunavir Plus Either Emtricitabine/Tenofovir or Abacavir/Lamivudine to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Infected Adults. Available from: https://clinicaltrials.gov/ct2/show/NCT02603107
3 Gallant J et al. (2017). Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 390(10107); 2063-2072
4 Sax PE et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017; 390(10107):2073-2082.