Phase 3 Randomized, Controlled Trial of Switching to Fixed-dose Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) from Boosted Protease Inhibitor-based Regimens in Virologically Suppressed Adults: Week 48 Results
Authors: Daar Eric , DeJesus Edwin , Ruane Peter , Crofoot Gordon , Oguchi Godson , Creticos Catherine , Rockstroh Jurgen K , Molina Jean-Michel , Koenig Ellen , Liu Ya-Pei , Andreatta Kristen , Graham Hiba , Cheng Andrew , Martin Hal , Quirk Erin 
Published: October 2017

Abstract

Background
Boosted protease inhibitor regimens (bPIs) are effective and often used in HIV-infected individuals with difficulties with adherence, but they can have drug–drug interactions and GI adverse effects. Bictegravir (B), a novel, potent integrase strand transfer inhibitor with a high barrier to resistance and low potential for drug–drug interactions, was coformulated with the recommended nucleoside reverse transcriptase inhibitor backbone emtricitabine (FTC)/tenofovir alafenamide (F/TAF) and demonstrated high efficacy and tolerability in randomized studies in treatment-naïve adults. This randomized Phase 3 study assesses efficacy and safety of switching to B/F/TAF from a multi-tablet regimen containing a bPI.

Methods
HIV-infected adults suppressed on regimens of boosted atazanavir (ATV) or darunavir (DRV) + abacavir/lamivudine (ABC/3TC) or FTC/tenofovir disoproxil fumarate (TDF) were randomized 1:1 to continue their current bPI regimen or switch to open-label coformulated B/F/TAF (50/200/25 mg) once daily. Primary endpoint was proportion with HIV-1 RNA ≥50 copies/mL (c/mL) at W48 (FDA snapshot). Noninferiority was assessed through 95.002% confidence intervals (CI) using a margin of 4%. Secondary endpoints included proportion with HIV-1 RNA &lt;50 c/mL and safety measures at W48.

Results
A total of 577 participants were randomized and treated with B/F/TAF (n = 290) or current bPI regimens (n = 287): 17% women, 26% Black, median age 48 years. Most were receiving a bPI with FTC/TDF (85%) at screening. At W48, switching to B/F/TAF was noninferior to continuing bPI with 1.7% in each group having HIV-1 RNA ≥50 c/mL (difference −0.0%; 95.002% CI −2.5% to 2.5%, P = 1.00); the proportion with HIV-1 RNA &lt;50 c/mL was 92.1% in B/F/TAF vs. 88.9% in bPI. No participant on B/F/TAF developed resistance to study drugs. One participant on DRV/ritonavir + ABC/3TC developed a treatment-emergent L74V mutation. Incidence of grade 3 or 4 AEs was similar (B/F/TAF 4%, bPI regimens 6%). No renal discontinuations or tubulopathy cases occurred with B/F/TAF.

Conclusion
Adults switching to B/F/TAF from a boosted PI maintained high rates of virologic suppression without resistance. B/F/TAF was safe and well tolerated.

Disclosures
E. Daar, Bristol-Myers Squibb: Consultant, Consulting fee. Gilead Sciences, Inc.: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support. Janssen: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support. Merck: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support. Teva Pharmaceuticals: Consultant and Scientific Advisor, Consulting fee. ViiV: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research support. E. DeJesus, Abbott Laboratories; Achillion Pharmaceuticals, Avexa, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Hoffmann LaRoche, Idenix, Janssen, Merck, Pfizer, Sangamo, Taimed, Tobira, and Vertex: Grant Investigator, Research grant. Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and Vertex: Scientific Advisor, Consulting fee. P. Ruane, Gilead: Investigator, Scientific Advisor and Shareholder, Consulting fee and Research support. Merck: Speaker’s Bureau, Speaker honorarium. Boehringer: Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium. Janssen: Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium. Abbott: Investigator, Scientific Advisor and Speaker’s Bureau, Research support and Speaker honorarium. Idenix: Investigator, Research support. ViiV: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium. BMS: Consultant, Investigator and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium. G. Crofoot, Gilead: Investigator and Scientific Advisor, Advisory honorarium and Research grant. ViiV: Investigator and Scientific Advisor, Advisory honorarium, Research grant and Research support. C. Creticos, Thera Technologies and ViiV Healthcare: Scientific Advisor, Consulting fee. Gilead sciences, Merck, and ViiV Healthcare: Investigator, Research support. Pfizer: Speaker’s Bureau, Speaker honorarium. J. K. Rockstroh, Abbvie: Consultant and Investigator, Consulting fee and Speaker honorarium. Gilead: Consultant, Investigator and Scientific Advisor, Consulting fee and Speaker honorarium. ViiV: Scientific Advisor, Consulting fee. Janssen: Investigator and Speaker at educational event, Speaker honorarium. J. M. Molina, Gilead, ViiV, Merck, Janssen, BMS and TEVA: Scientific Advisor, Speaker honorarium. Y. P. Liu, Gilead: Employee and Shareholder, Salary and Shareholder. K. Andreatta, Gilead: Employee and Shareholder, Salary and Shareholder. H. Graham, Gilead Sciences: Employee and Shareholder, Salary. A. Cheng, Gilead: Employee and Shareholder, Salary. H. Martin, Gilead Sciences: Employee, Salary. E. Quirk, Gilead: Employee and Shareholder, Salary