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

Samir K Gupta, Frank A Post, José R Arribas, Joseph J Eron Jr, 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, Hal Martin, Diana Brainard, Devi SenGupta, Moupali Das, Samir K Gupta, Frank A Post, José R Arribas, Joseph J Eron Jr, 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, Hal Martin, Diana Brainard, Devi SenGupta, Moupali Das

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.

Figures

Fig. 1
Fig. 1
Characteristics of studies included in the integrated analysis.
Fig. 2
Fig. 2
Cases of proximal renal tubulopathy and renal adverse events leading to study drug discontinuation across 26 clinical studies.
Fig. 3
Fig. 3
Longitudinal changes in renal laboratory parameters.
Fig. 4
Fig. 4
Longitudinal changes in renal biomarkers.

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