Switching tenofovir disoproxil fumarate to tenofovir alafenamide in a real life setting: what are the implications?


Journal

HIV medicine
ISSN: 1468-1293
Titre abrégé: HIV Med
Pays: England
ID NLM: 100897392

Informations de publication

Date de publication:
07 2020
Historique:
received: 19 05 2019
revised: 10 12 2019
accepted: 19 12 2019
pubmed: 18 2 2020
medline: 29 9 2021
entrez: 18 2 2020
Statut: ppublish

Résumé

Development of novel antiretrovirals aims at reducing long-term toxicities. Tenofovir disoproxil fumarate (TDF) has been associated with potential nephrotoxicity. The aim of our study was to assess the impact of switching from TDF to tenofovir alafenamide (TAF) on functional nephropathy and lipid parameters in a real-life setting. We retrospectively analysed data from 347 HIV-infected patients switching from a TDF- to a TAF-containing regimen between April and December 2016. Sociodemographic, clinical and laboratory data were collected at TDF-to-TAF switch, and at 3 and 6 months thereafter. Proteinuria and albuminuria were classified according to Kidney Diseases Improving Global Outcomes (KDIGO) guidelines. At time of switch, moderately and severely increased proteinuria was detected in 32% and 8% of patients, respectively; however, urine dipstick analysis was negative in 84% and 42%, respectively. Moderately and severely increased albuminuria was found in 17% and 3% of patients, respectively. In patients with a urinary protein-to-creatinine ratio (UPCR) ≥ 150 mg/g, the mean value declined from 416 mg/g at baseline to 272 mg/g (P < 0.001) and 242 mg/g (P < 0.001) after 3 and 6 months, respectively. Patients with an albumin-to-creatinine ratio (UACR) ≥ 30 mg/g showed no significant decrease of albuminuria. Mean total cholesterol increased from 187 mg/dL at baseline to 202 (P < 0.001) and 208 mg/dL (P < 0.001) at 3 and 6 months, respectively, and mean low-density lipoprotein (LDL) cholesterol increased from 114 mg/dL at baseline to 124 (P < 0.001) and 128 mg/dL (P < 0.001), respectively. As mean high-density lipoprotein (HDL) cholesterol increased from 50 mg/dL at baseline to 54 (P < 0.001) and 57 mg/dL (P < 0.001) at 3 and 6 months, respectively, the LDL:HDL ratio remained stable. In an aging HIV-infected cohort, proteinuria and albuminuria were common findings and were underdiagnosed via urine dipstick. Our real-life data suggest that laboratory markers of moderately/severely increased proteinuria improved after TDF-to-TAF-switch. Lipid profiles were not aggravated. Long-term follow-up is needed to determine the clinical benefit of the TDF-to-TAF switch.

Identifiants

pubmed: 32065713
doi: 10.1111/hiv.12840
doi:

Substances chimiques

Cholesterol, LDL 0
Tenofovir 99YXE507IL
tenofovir alafenamide EL9943AG5J
Alanine OF5P57N2ZX

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

378-385

Informations de copyright

© 2019 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

Références

Wyatt CM, Hoover DR, Shi Q et al. Pre-existing albuminuria predicts AIDS and non-AIDS mortality in women initiating antiretroviral therapy. Antivir Ther (Lond.) 2011; 16: 591-596.
Choi AI, Li Y, Deeks SG, Grunfeld C, Volberding PA, Shlipak MG. Association between kidney function and albuminuria with cardiovascular events in HIV-infected persons. Circulation 2010; 121: 651-658.
Jafari A, Khalili H, Dashti-Khavidaki S. Tenofovir-induced nephrotoxicity: incidence, mechanism, risk factors, prognosis and proposed agents for prevention. Eur J Clin Pharmacol 2014; 70: 1029-1040.
Lee WA, He G-X, Eisenberg E et al. Selective intracellular activation of a novel prodrug of the human immunodeficiency virus reverse transcriptase inhibitor tenofovir leads to preferential distribution and accumulation in lymphatic tissue. Antimicrob Agents Chemother 2005; 49: 1898-1906.
Sax PE, Zolopa A, Brar I et al. Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. J Acquir Immune Defic Syndr 2014; 67: 52-58.
Sax PE, Wohl D, Yin MT et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet 2015; 385: 2606-2615.
Eron JJ, Orkin C, Gallant J et al. A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. AIDS 2018; 32: 1431-1442.
Gallant JE, Daar ES, Raffi F et al. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial. Lancet HIV 2016; 3: e158-e165.
Orkin C, Molina JM, Negredo E et al. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial. Lancet HIV 2018; 5: e23-e34.
Mills A, Arribas JR, Andrade-Villanueva J et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study. Lancet Infect Dis 2016; 16: 43-52.
Mills A, Crofoot G, McDonald C et al. Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease Inhibitor-Based Single-Tablet Regimen for Initial HIV-1 Therapy: A Randomized Phase 2 Study. J Acquir Immune Defic Syndr 2015; 69: 439-445.
Members KB KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3: 19-62.
Shafran SD, Di Perri G, Esser S, Lelièvre J-D, Parczewski M. Planning HIV therapy to prevent future comorbidities: patient years for tenofovir alafenamide. HIV Med 2019; 20 (Suppl 7): 1-16.
EACS Governing Board. EACS Guidelines, Version 10.0, 2019.
Gravemann S, Brinkkoetter PT, Vehreschild JJ et al. Low-grade proteinuria is highly prevalent in HIV-positive patients on antiretroviral treatment. AIDS 2014; 28: 1783-1789.
Zeder AJ, Hilge R, Schrader S, Bogner JR, Seybold U. Medium-grade tubular proteinuria is common in HIV-positive patients and specifically associated with exposure to tenofovir disoproxil Fumarate. Infection 2016; 44: 641-649.
Gupta SK, Post FA, Arribas JR et al. Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials. AIDS 2019; 33: 1455-1465.
Santos JR, Saumoy M, Curran A et al. The lipid-lowering effect of tenofovir/emtricitabine: a randomized, crossover, double-blind, placebo-controlled trial. Clin Infect Dis 2015; 61: 403-408.
Tungsiripat M, Kitch D, Glesby MJ et al. A pilot study to determine the impact on dyslipidemia of adding tenofovir to stable background antiretroviral therapy: ACTG 5206. AIDS 2010; 24: 1781-1784.
Crane HM, Grunfeld C, Willig JH et al. Impact of NRTIs on lipid levels among a large HIV-infected cohort initiating antiretroviral therapy in clinical care. AIDS 2011; 25: 185-195.
Millán J, Pintó X, Muñoz A et al. Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention. Vasc Health Risk Manag 2009; 5: 757-765.

Auteurs

C Schwarze-Zander (C)

Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.

H Piduhn (H)

Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.

C Boesecke (C)

Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.

S Schlabe (S)

Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.

B Stoffel-Wagner (B)

Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.

J C Wasmuth (JC)

Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.

C P Strassburg (CP)

Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.

J K Rockstroh (JK)

Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH