Switching From TDF to TAF in HIV/HBV-Coinfected Individuals With Renal Dysfunction

A Prospective Cohort Study

Bernard Surial, MD; Charles Béguelin, MD; Jean-Philippe Chave, MD; Marcel Stöckle, MD; Noémie Boillat-Blanco, MD; Thanh Doco-Lecompte, MD; Enos Bernasconi, MD; Jan Fehr, MD; Huldrych F. Günthard, MD; Patrick Schmid, MD; Laura N. Walti, MD; Hansjakob Furrer, MD; Andri Rauch, MD; Gilles Wandeler, MD

Disclosures

J Acquir Immune Defic Syndr. 2020;85(2):227-232. 

In This Article

Abstract and Introduction

Abstract

Background: Whereas tenofovir disoproxil fumarate (TDF) can lead to renal adverse events, tenofovir alafenamide (TAF) has a more favorable renal safety profile. However, the impact of replacing TDF with TAF on renal function and liver parameters among HIV/hepatitis B virus (HBV)-coinfected individuals with renal dysfunction remains unclear.

Methods: We included all participants from the Swiss HIV Cohort Study with an HIV/HBV coinfection who switched from TDF to TAF and had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 and a suppressed HIV viral load (<200 cp/mL). We assessed changes in eGFR, urine protein-to-creatinine ratio, and alanine aminotransferase (ALT) after 1 year using mixed-effect models with interrupted time series.

Results: Among 106 participants (15.1% women, median age 53 years), eGFR was 60–89 mL/min/1.73 m2 in 84 (79.2%) and <60 mL/min/1.73 m2 in 22 (20.8%) individuals at the time of switch. One year after the switch from TDF to TAF, individuals with an eGFR between 60 and 89 mL/min/1.73 m2 experienced increases in eGFR of 3.2 mL/min/1.73 m2 (95% confidence interval [CI] 1.2 to 5.2), whereas those with an eGFR <60 mL/min/1.73 m2 experienced improvements of 6.2 mL/min/1.73 m2 (95% CI 2.4 to 10.0). Urine protein-to-creatinine ratio decreased overall (−6.3 mg/mmol, 95% CI −10.0 to −2.7), and ALT levels declined in patients with elevated baseline levels (−11.8 IU/L, 95% CI −17.3 to −6.4) 1 year after replacing TDF with TAF.

Conclusions: Switching from TDF to TAF among HIV/HBV-coinfected individuals with renal impairment led to improvements in eGFR, a decline in proteinuria, and to ALT normalization in those with elevated ALT levels.

Introduction

Tenofovir-based antiretroviral therapy (ART) is the mainstay of treatment for HIV/hepatitis B virus (HBV) coinfection. Whereas resistance to lamivudine develops in a significant proportion of HBV-infected individuals, HBV resistance to tenofovir is rare.[1] In addition, liver fibrosis seems to improve with the use of tenofovir, and its use is associated with a reduced incidence of cirrhosis and hepatocellular carcinoma.[2–4]

However, tenofovir disoproxil fumarate (TDF) has been associated with renal side effects, such as proximal renal tubulopathy.[5] Moreover HBV infection itself can lead to glomerular and tubular renal injury and, rarely, to the development of end-stage renal disease.[6] Tenofovir alafenamide (TAF) is a prodrug with a favorable renal safety profile compared with TDF mainly because tenofovir plasma concentrations are reduced by approximately 90%.[7,8] Because the studies that confirmed the renal safety of TAF in HIV/HBV-infected individuals mainly enrolled individuals without renal impairment,[7,9] we evaluated the impact of replacing TDF with TAF on estimated glomerular filtration rate (eGFR), urine protein-to-creatinine ratio, and alanine aminotransferase (ALT) levels in HIV/HBV-coinfected individuals with renal dysfunction using data from the Swiss HIV Cohort Study (SHCS).

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