Format

Send to

Choose Destination
AIDS. 2019 Jul 15;33(9):1455-1465. doi: 10.1097/QAD.0000000000002223.

Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials.

Author information

1
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
2
King's College Hospital NHS Foundation Trust, London, UK.
3
Instituto de Investigación Hospital Universitario La Paz, Hospital Universitario La Paz, Madrid, Spain.
4
Division of Infectious Diseases, Department of Medicine, UNC School of Medicine.
5
Division of Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
6
Sexual Health and Clinical Trials, Royal Sussex County Hospital, Brighton, UK.
7
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
8
Infectious Disease Medical Center, Hamburg.
9
Universitatsklinikum, Essen, Germany.
10
Chelsea and Westminster Hospital and St Stephens AIDS Trust, London, UK.
11
Infectious Diseases Service, Hospital Universitario de Bellvitge, Barcelona, Spain.
12
Mortimer Market Centre.
13
Barts Health NHS Trust, Ambrose King Centre, Royal London Hospital, London, UK.
14
University Hospital Bonn, Bonn, Germany.
15
Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands.
16
Universitat de Vic-Universitat Central de Catalunya, Barcelona, Spain.
17
Department of Clinical Investigations, Whitman-Walker Health, Washington, District of Columbia.
18
Departments of Biometrics and HIV & Emerging Viral Infections Clinical Research, Gilead Sciences, Inc., Foster City, California, USA.

Abstract

OBJECTIVE:

Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has been associated with improvement in markers of renal dysfunction in individual randomized 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-naive and antiretroviral switch studies to compare the incidence of proximal renal tubulopathy and discontinuation due to renal adverse events between participants taking TAF-containing regimens vs. those taking TDF-containing regimens. We performed secondary analyses from seven large randomized studies (two treatment-naive and five switch studies) to compare incidence of renal adverse events, 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 9322 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 proximal renal tubulopathy in participants receiving TAF vs. 10 cases in those receiving TDF (P < 0.001), and fewer individuals on TAF (3/6360) vs. TDF (14/2962) (P < 0.001) discontinued due to a renal adverse event. Participants initiating TAF-based 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.

Supplemental Content

Full text links

Icon for Wolters Kluwer
Loading ...
Support Center