Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate

A pooled analysis of 26 clinical trials

Samir Gupta, Frank A. Post, José R. Arribas, Joseph J. Eron, David A. Wohl, Amanda E. Clarke, Paul E. Sax, Hans Jürgen Stellbrink, Stefan Esser, Anton L. Pozniak, Daniel Podzamczer, Laura Waters, Chloe Orkin, Jürgen K. Rockstroh, Tatiana Mudrikova, Eugenia Negredo, Richard A. Elion, Susan Guo, Lijie Zhong, Christoph Carter & 4 others Hal Martin, Diana Brainard, Devi Sengupta, Moupali Das

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1455-1465
Number of pages11
JournalAIDS
Volume33
Issue number9
DOIs
StatePublished - Jul 15 2019

Fingerprint

Tenofovir
Clinical Trials
Kidney
Safety
Creatinine
Incidence
Biomarkers
GS-7340
beta 2-Microglobulin
Retinol-Binding Proteins

Keywords

  • adverse drug event
  • drug safety biomarkers
  • HAART
  • HIV
  • proximal renal tubular dysfunction
  • renal fanconi syndrome
  • tenofovir disoproxil fumarate

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Gupta, S., Post, F. A., Arribas, J. R., Eron, J. J., Wohl, D. A., Clarke, A. E., ... Das, M. (2019). Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: A pooled analysis of 26 clinical trials. AIDS, 33(9), 1455-1465. https://doi.org/10.1097/QAD.0000000000002223

Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate : A pooled analysis of 26 clinical trials. / Gupta, Samir; Post, Frank A.; Arribas, José R.; Eron, Joseph J.; Wohl, David A.; Clarke, Amanda E.; Sax, Paul E.; Stellbrink, Hans Jürgen; Esser, Stefan; Pozniak, Anton L.; Podzamczer, Daniel; Waters, Laura; Orkin, Chloe; Rockstroh, Jürgen K.; Mudrikova, Tatiana; Negredo, Eugenia; Elion, Richard A.; Guo, Susan; Zhong, Lijie; Carter, Christoph; Martin, Hal; Brainard, Diana; Sengupta, Devi; Das, Moupali.

In: AIDS, Vol. 33, No. 9, 15.07.2019, p. 1455-1465.

Research output: Contribution to journalArticle

Gupta, S, Post, FA, Arribas, JR, Eron, JJ, Wohl, DA, Clarke, AE, Sax, PE, Stellbrink, HJ, Esser, S, Pozniak, AL, Podzamczer, D, Waters, L, Orkin, C, Rockstroh, JK, Mudrikova, T, Negredo, E, Elion, RA, Guo, S, Zhong, L, Carter, C, Martin, H, Brainard, D, Sengupta, D & Das, M 2019, 'Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: A pooled analysis of 26 clinical trials', AIDS, vol. 33, no. 9, pp. 1455-1465. https://doi.org/10.1097/QAD.0000000000002223
Gupta, Samir ; Post, Frank A. ; Arribas, José R. ; Eron, Joseph J. ; Wohl, David A. ; Clarke, Amanda E. ; Sax, Paul E. ; Stellbrink, Hans Jürgen ; Esser, Stefan ; Pozniak, Anton L. ; Podzamczer, Daniel ; Waters, Laura ; Orkin, Chloe ; Rockstroh, Jürgen K. ; Mudrikova, Tatiana ; Negredo, Eugenia ; Elion, Richard A. ; Guo, Susan ; Zhong, Lijie ; Carter, Christoph ; Martin, Hal ; Brainard, Diana ; Sengupta, Devi ; Das, Moupali. / Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate : A pooled analysis of 26 clinical trials. In: AIDS. 2019 ; Vol. 33, No. 9. pp. 1455-1465.
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T2 - A pooled analysis of 26 clinical trials

AU - Gupta, Samir

AU - Post, Frank A.

AU - Arribas, José R.

AU - Eron, Joseph J.

AU - Wohl, David A.

AU - Clarke, Amanda E.

AU - Sax, Paul E.

AU - Stellbrink, Hans Jürgen

AU - Esser, Stefan

AU - Pozniak, Anton L.

AU - Podzamczer, Daniel

AU - Waters, Laura

AU - Orkin, Chloe

AU - Rockstroh, Jürgen K.

AU - Mudrikova, Tatiana

AU - Negredo, Eugenia

AU - Elion, Richard A.

AU - Guo, Susan

AU - Zhong, Lijie

AU - Carter, Christoph

AU - Martin, Hal

AU - Brainard, Diana

AU - Sengupta, Devi

AU - Das, Moupali

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N2 - 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.

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KW - drug safety biomarkers

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KW - renal fanconi syndrome

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