726. Strategic Simplification: The Efficacy and Safety of Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) plus Darunavir (DRV) in Treatment-Experienced HIV-1 infected Adults (NCT01968551)
Session: Oral Abstract Session: Antiretroviral Therapy: New Drugs and Treatment Outcomes
Friday, October 9, 2015: 10:45 AM
Room: 25--ABC
Background:

Strategic simplification of an antiretroviral regimen with high pill burden and dosing frequency is a priority for treatment-experienced patients with multi-drug resistance. A single tablet with co-formulated E/C/F/TAF has demonstrated high efficacy and improved renal and bone safety compared to E/C/F/TDF in Phase 3 clinical trials. This study evaluated the efficacy and safety of switching to E/C/F/TAF +DRV in patients with ≥ 2-class resistance, including TDF resistance mutations (K65R, ≤3 TAMs). 

Methods:

Virologically suppressed adults (N=135) on a DRV-containing regimen for ≥ 4months, with two prior failed regimens, and no history of Q151M, T69ins, or DRV RAMs, were randomized 2:1 to open-label E/C/F/TAF +DRV or to continue baseline regimen (BR). Week (W) 24 viral suppression (HIV-1 RNA <50c/mL) by FDA snapshot analysis and safety data are reported. 

Results:

Participants were older (median age 49), 25% female, 45% black, and 14% Hispanic. At entry, the median pills/regimen was 5, with 65% taking a twice-daily regimen, and a majority (58%) on a TDF-containing regimen. Viral suppression was maintained in 96.6% (86/89) in the E/C/F/TAF +DRV arm and 91.3% (42/46) in the BR arm (95%CI: -3.4%, 17.4%). In the E/C/F/TAF +DRV arm, 2 patients had viremia at W24 but were suppressed at W36 and W48; 1 and 4 persons were missing data in the E/C/F/TAF +DRV and BR arms, respectively. There was no emergence of resistance. There were no differences in the median change in eGFR [2.5 in the E/C/F/TAF+DRV vs. -0.1mL/min in the BR arm (p=0.62)] or urine protein/creatinine (Cr) ratio [-14% in the E/C/F/TAF +DRV arm vs. -4% in BR arm (p=0.21)]. Specific markers of proximal tubular proteinuria improved with E/C/F/TAF +DRV: median urine beta-2M/Cr decreased 35% (p<.001) and median urine RBP/Cr decreased 17% (p=.019), compared to increases of 11% and 13% respectively in the BR arm. There were no drug-related SAEs and no AEs leading to treatment discontinuation. 

Conclusion:

Through W24, strategic simplification to E/C/F/TAF + DRV (two pills once daily) maintained viral suppression, and the switch to TAF was associated with significant improvement in proximal tubular proteinuria. E/C/F/TAF +DRV may offer an attractive option for treatment-experienced patients on complex multi-tablet regimens.

Gregory Huhn, MD, MPHTM1, Pablo Tebas, MD, FIDSA2, Joel Gallant, MD, MPH, FIDSA3, Timothy Wilkin, MD/MPH, FIDSA4, Andrew Cheng, MD PhD5, Mingjin Yan, PhD6, Christian Callebaut, PhD7, Marshall Fordyce, MD8, Moupali Das, MD, MPH9 and Scott Mccallister, MD8, (1)Infectious Diseases, Ruth M Rothstein CORE Center, Chicago, IL, (2)Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, (3)Southwest CARE Center, Santa Fe, NM, (4)Division of Infectious Diseases, Weill Medical College of Cornell University, New York, NY, (5)Development Operations, Gilead Sciences, Foster City, CA, (6)Biostatistics, Gilead Sciences, Inc., Foster City, CA, (7)Biology, Gilead Sciences, Inc., Foster City, CA, (8)HIV Clinical Research, Gilead Sciences, Foster City, CA, (9)Gilead Sciences, Inc., Foster City, CA

Disclosures:

G. Huhn, Gilead: Consultant and Investigator , Consulting fee and Research support
Merck: Grant Investigator , Grant recipient
GSK/Viiv: Consultant and Investigator , Consulting fee and Research support
Janssen: Grant Investigator , Grant recipient

P. Tebas, Merck: Consultant , Consulting fee
Glaxo: Consultant , Consulting fee

J. Gallant, AbbVie: Investigator , Research support
Bristol-Myers Squibb: Investigator and Scientific Advisor , Consulting fee and Research support
Gilead Sciences: Investigator and Scientific Advisor , Consulting fee and Research support
Janssen Therapeutics: Investigator and Scientific Advisor , Consulting fee and Research support
Merck & Co.: Investigator and Scientific Advisor , Consulting fee and Research support
Sangamo BioSciences: Investigator , Research support
ViiV Healthcare: Investigator and Scientific Advisor , Consulting fee and Research support

T. Wilkin, GSK/Viiv: Consultant , Consulting fee
BMS: Investigator , Grant recipient
Gilead: Investigator , Grant recipient

A. Cheng, Gilead Sciences: Employee and Shareholder , Salary

M. Yan, Gilead Sciences, Inc: Employee and Shareholder , Salary

C. Callebaut, Gilead Sciences, Inc.: Employee and Shareholder , Salary

M. Fordyce, Gilead Sciences, Inc.: Employee and Shareholder , Salary

M. Das, Gilead Sciences, Inc.: Employee and Shareholder , Salary

S. Mccallister, Gilead Sciences, Inc.: Employee and Shareholder , Salary

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.