Bictegravir is an investigational integrase inhibitor that is dosed once daily, unboosted. It is active in vitro against many viruses with integrase resistance mutations. A Phase 2 double-blind placebo-controlled study randomized treatment-naive patients (n = 98) 2:1 to bictegravir + TAF/FTC or dolutegravir + TAF/FTC. Results from this study were presented at CROI and concurrently published in Lancet HIV. At 48 weeks, HIV suppression to <50 copies/mL was seen in 97% of the bictegravir group and 91% of the dolutegravir group by snapshot analysis; the study was not powered for statistical comparisons. In the few patients with virologic failure, no integrase or NRTI resistance was seen in the bictegravir group, while 1 patient in the dolutegravir group developed an integrase mutation (T97A). Adverse effects were similar overall, but more patients in the bictegravir group developed elevations in AST, ALT, and CPK.
Clinical Bottom Line
In this small study, bictegravir compared very favorably with our current gold standard anchor drug, dolutegravir. Bictegravir has yet to be studied in patients with advanced disease, chronic kidney disease, or viral hepatitis, and it has not been given with NRTI backbones other than TAF/FTC. We will need more data on efficacy, safety, and resistance from future studies to better understand its strengths and weaknesses. We also will need to learn more about drug-drug interactions involving bictegravir--researchers reported that bictegravir is metabolized by both CYP P450 and UGT 1A1 but did not present enough data to clarify the potential impact of this process. Phase 3 trials evaluating a coformulation of bictegravir/TAF/FTC are under way both in ARV-naive individuals and in patients switching from other regimens. It should be noted that the dose of bictegravir selected for the coformulation (50 mg) is less than that studied in the Phase 2 study (75 mg).
- Sax PE, DeJesus E, Crofoot G, et al. Randomized trial of bictegravir or dolutegravir with FTC/TAF for initial HIV therapy. In: Program and abstracts of the 2017 Conference on Retroviruses and Opportunistic Infections; February 13-16, 2017; Seattle. Abstract 41.
- Sax PE, DeJesus E, Crofoot G, et al. Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection: a randomised, double-blind, phase 2 trial. Lancet HIV. 2017 Apr;4(4):e154-e160.