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Renal safety of tenofovir alafenamide vs tenofovir disoproxil fumarate

A pooled analysis of 26 clinical trials

Gupta, Samir K.a; Post, Frank A.b; Arribas, José R.c; Jr, Joseph J. Erond; Wohl, David A.e; Clarke, Amanda E.f; Sax, Paul E.g; Stellbrink, Hans-Jürgenh; Esser, Stefani; Pozniak, Anton L.j; Podzamczer, Danielk; Waters, Laural; Orkin, Chloem; Rockstroh, Jürgen K.n; Mudrikova, Tatianao; Negredo, Eugeniap; Elion, Richard A.q; Guo, Susanr; Zhong, Lijier; Carter, Christophr; Martin, Halr; Brainard, Dianar; Sengupta, Devir; Das, Moupalir

doi: 10.1097/QAD.0000000000002223
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Objective: Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has been associated with improvement in markers of renal dysfunction in individual randomised trials; however the comparative incidence of clinically significant renal events remains unclear.

Design: We used a pooled data approach to increase the person-years of drug exposure analysed, maximizing our ability to detect differences in clinically significant outcomes.

Methods: We pooled clinical renal safety data across 26 treatment naïve and antiretroviral switch studies in order to compare the incidence of proximal renal tubulopathy (PRT) and discontinuation due to renal adverse events (AEs) between participants taking TAF-containing regimens versus those taking TDF-containing regimens. We performed secondary analyses from seven large randomised studies (two treatment-naïve and five switch studies) to compare incidence of renal AEs, treatment-emergent proteinuria, changes in serum creatinine, creatinine clearance, and urinary biomarkers (albumin, beta-2-microglobulin, and retinol binding protein to creatinine ratios).

Results: Our integrated analysis included 9,322 adults and children with HIV (n = 6360 TAF, n = 2962 TDF) with exposure of 12,519 person-years to TAF and 5947 to TDF. There were no cases of PRT in participants receiving TAF versus 10 cases in those receiving TDF (p < 0.001), and fewer individuals on TAF (3/6360) versus TDF (14/2962) (p < 0.001) discontinued due to a renal AE. Participants initiating TAF- vs. TDF-based regimens had more favourable changes in renal biomarkers through 96 weeks of therapy.

Conclusion: These pooled data from 26 studies, with over 12,500 person-years of follow-up in children and adults, support the comparative renal safety of TAF over TDF.

This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

aDepartment of Medicine at the Indiana University School of Medicine, Indianapolis, IN, USA

bKing's College Hospital NHS Foundation Trust, London, UK

cHospital Universitario La Paz, Instituto de Investigación Hospital La Paz, Madrid, ES

dDepartment of Medicine, Division of Infectious Diseases, UNC School of Medicine, Chapel Hill, NC, USA

eDivision of Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

fSexual Health and Clinical Trials, Royal Sussex County Hospital, Brighton, UK

gBrigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

hInfectious Disease Medical Center, Hamburg, DE

iUniversitatsklinikum, Essen, DE

jChelsea and Westminster Hospital and St Stephens AIDS Trust, London, UK

kInfectious Diseases Service of the Hospital Universitario de Bellvitge, Barcelona, ES

lMortimer Market Center, London, UK

mBarts Health NHS Trust, Royal London Hospital, Ambrose King Centre, London, UK

nUniversity Hospital Bonn, Bonn, DE

oDepartment of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, NL

pUniversitat de Vic-Universitat Central de Catalunya, Barcelona, ES

qDepartment of Clinical Investigations, Whitman Walker Health, Washington, DC, USA

rGilead Sciences, Inc., Foster City, CA, USA.

Correspondence to Samir K. Gupta, MD, MS, Indiana University School of Medicine, Division of Infectious Diseases, Emerson Hall, Suite 421, 545 Barnhill Drive, Indianapolis, IN 46202, USA, Tel+: 317-274-7926; Fax+: 317-274-1587; e-mail: sgupta1@iu.edu; Moupali Das, MD, MPH, Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94494 USA; Tel+: 650-522-4511; e-mail: Moupali.Das@gilead.com.

Received 20 December, 2018

Revised 15 February, 2019

Accepted 18 February, 2019

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