725. Switching from a Tenofovir Disoproxil Fumarate (TDF) to a Tenofovir Alafenamide (TAF)-Based Single Tablet Regimen (STR): Week 48 Data in HIV-1 Infected Virologically Suppressed Adults
Session: Oral Abstract Session: Antiretroviral Therapy: New Drugs and Treatment Outcomes
Friday, October 9, 2015: 10:30 AM
Room: 25--ABC

Background: TAF is a tenofovir (TFV) prodrug coformulated into a STR containing elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/TAF 10mg (E/C/F/TAF).  . Week 48 data in adults on elvitegravir/cobicistat/emtricitabine/TDF (E/C/F/TDF) randomized to switch to a once-daily E/C/F/TAF regimen or to continue E/C/F/TDF are described.

Methods: GS-US-292-0109 is a study in virologically suppressed (HIV-1 RNA <50 copies/ml) adults on a TDF-containing regimen randomized to take open label E/C/F/TAF or to continue a prior regimen. These data are from a pre-specified sub-analysis of 459 patients on blinded E/C/F/TDF for at least 48 weeks who were randomized 2:1 to open label E/C/F/TAF or E/C/F/TDF.

Results: At Week 48, 301/306 (98.4%) of those switched to E/C/F/TAF and 149/153 (97.4%) of those continuing E/C/F/TDF had HIV-1 RNA <50 c/mL (95% CI: -1.9% - 3.9%). Treatment discontinuation unrelated to AE: 1/306 (0.3%) on E/C/F/TAF and 1/153 (0.7%) on E/C/F/TDF. Bone mineral density (BMD) and serum creatinine both improved significantly in patients on E/C/F/TAF (see table). Likewise, quantitative proteinuria and tubular proteinuria were significantly improved for patients switching to E/C/F/TAF compared to those continuing E/C/F/TDF. Serum creatinine mean change (mg/dL) from baseline: E/C/F/TAF, -0.01; E/C/F/TDF, +0.03 (p<0.001).

 

Median % Change from Baseline to W48

E/C/F/TAF

E/C/F/TDF

Significance

BMD Hip (SD)

+1.15 (2.4)

-0.17 (2.9)

p<0.001

BMD Spine (SD)

+1.33 (3.6)

-0.50 (3.4)

Urine Protein: Creatinine

-16.2

+13.7

Urine Albumin: Creatinine

-17.7

+7.7

Retinol Binding Protein: Creatinine

-28.6

+27.4

Beta-2-Microglobulin: Creatinine

-43.3

+20.8

E/C/F/TAF patients had statistically higher changes from baseline in fasted lipid tests; the total cholesterol: HDL ratio change was: E/C/F/TAF, +0.2; E/C/F/TDF, +0.1 (p=0.48).

 

Conclusion: At Week 48, patients who switched from E/C/F/TDF to E/C/F/TAF remained on treatment and maintained high virologic control, had significantly improved hip/spine BMD, serum creatinine, and had significantly less general proteinuria and specific proximal tubular proteinuria than those remaining on E/C/F/TDF. Longer term data are needed to understand the clinical relevance of lipid changes in the TAF arm.

Melanie Thompson, MD, AIDS Research Consortium of Atlanta, Atlanta, GA, Javier Morales-Ramirez, MD, Clinical Research Puerto Rico, Inc., San Juan, PR, Cheryl Mcdonald, MD, Tarrant County Infection Disease Associates, Fort Worth, TX, Anita Rachlis, MD, Sunnybrook Health Sciences Centre Odette Cancer Centre, Toronto, ON, Canada, Christian Hoffmann, MD, ICH Study Center, Hamburg, Germany, Adriano Lazzarin, MD, University Vita-Salute San Raffaele, Milano, Italy, Gordon Crofoot, MD, Gordon E Crofoot MD PA, Crofoot Research, Houston, TX, Houston, TX, Andrew Plummer, PhD, Gilead Sciences, Foster City, CA, Ya-Pei Liu, PhD, Gilead Sciences, Inc., Foster City, CA, Andrew Cheng, MD PhD, Development Operations, Gilead Sciences, Foster City, CA and Scott Mccallister, MD, Clinical Research, Gilead Sciences, Foster City, CA

Disclosures:

M. Thompson, Gilead Sciences: Investigator , Research support
Bristol Myers Squibb, Inc.: Investigator , Research support
Geo Vax, Inc: Investigator , Research support
Kowa Research Institute: Investigator , Research support
Pfizer Inc: Investigator , Research support
Janssen/Tibotec Therapeutics: Investigator , Research support
Merck & Co: Investigator , Research support
Tobira Therapeutics: Investigator , Research support
ViiV Healthcare: Investigator , Research support

J. Morales-Ramirez, Gilead Sciences: Investigator , Research support

C. Mcdonald, Gilead Sciences: Investigator , Scientific Advisor and Speaker's Bureau , Research support
ViiV: Investigator and Speaker's Bureau , Research support
BMS: Investigator and Speaker's Bureau , Research support
Merck: Investigator , Research support
Janssen: Investigator , Research support

A. Rachlis, Gilead Sciences: Investigator and Scientific Advisor , Research support
Viiv: Investigator and Scientific Advisor , Research support
Merck: Investigator and Scientific Advisor , Research support
Janssen: Speaker's Bureau , Research support

C. Hoffmann, Gilead Sciences: Consultant , Investigator and Speaker's Bureau , Research support
AbbVie: Consultant , Investigator and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
Boehringer Ingelheim: Consultant , Investigator and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
Bristol Myers-Squibb: Consultant , Investigator and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
HEXAL: Consultant , Investigator and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
Janssen-Cilag: Consultant , Investigator and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
Merck Sharp Dohme: Consultant , Investigator and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
ViiV: Consultant , Investigator and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium

A. Lazzarin, Gilead Sciences: Investigator , Research support

G. Crofoot, Gilead Sciences: Investigator and Scientific Advisor , Research support
Glaxo: Investigator , Research support
Pfizer: Investigator , Research support
ViiV: Investigator , Research support
Janssen: Investigator , Research support
Sangamo Biosciences: Investigator , Research support
Merck: Investigator , Research support

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

Y. P. Liu, Gilead Sciences: Employee and Shareholder , Salary

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

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

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