LB-4. 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
Session: Oral Abstract Session: Late Breaker Oral Abstracts
Saturday, October 7, 2017: 11:00 AM
Room: 02
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 <50 c/mL and safety measures at W48.

Results: 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 yrs. 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 <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.

Eric Daar, MD1, Edwin DeJesus, MD2, Peter Ruane, MD3, Gordon Crofoot, MD4, Godson Oguchi, MD5, Catherine Creticos, MD6, Jurgen K Rockstroh, MD7, Jean-Michel Molina, MD, PhD8, Ellen Koenig, MD9, Ya-Pei Liu, PhD10, Kristen Andreatta, PhD10, Hiba Graham, Pharm D10, Andrew Cheng, MD PhD10, Hal Martin, MD, MPH10 and Erin Quirk, MD10, (1)1124 W. Carson St,, Harbor-UCLA Medical Center, Torrance, CA, (2)Orlando Immunology Center, Orlando, FL, (3)Ruane Clinical Research Group, Inc., Los Angeles, CA, (4)The Crofoot Research Center, Houston, TX, (5)Midland Florida Clinical Research Center, LLC, Deland, FL, (6)Howard Brown Health Center, Chicago, IL, (7)Department of Medicine I, Bonn University Hospital, Venusburg, Germany, (8)Department of Infectious Diseases, Saint-Louis Hospital,, Paris, France, (9)Medicine, Inst.Domin Estudio Virologicos, Santo Domingo, Dominican Republic, (10)Gilead Sciences, Foster City, CA

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

G. Oguchi, None

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

E. Koenig, None

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

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 4th with the exception of research findings presented at the IDWeek press conferences.