Changes in renal function after switching from TDF to TAF in HIV-infected individuals: a prospective cohort study.

BACKGROUND Replacing tenofovir disoproxil fumarate (TDF) with tenofovir alafenamide (TAF) improves renal tubular markers in HIV-infected individuals, but the impact on estimated glomerular filtration rate (eGFR) remains unclear. METHODS We included all participants from the Swiss HIV Cohort Study who switched from a TDF to a TAF-containing antiretroviral regimen or continued TDF. We estimated changes in eGFR and urine protein-to-creatinine ratio (UPCR) after 18 months using mixed-effect models. RESULTS Of 3'520 participants (26.6% women, median age 50 years), 2'404 (68.5%) switched to TAF. Prior to switch, 1'664 (47.3%) had an eGFR <90 mL/min, and 1'087 (30.9%) a UPCR ≥15 mg/mmol. In patients with a baseline eGFR ≥90 mL/min, eGFR decreased with the use of TDF and TAF (-1.7 ml/min). Switching to TAF was associated with increases in eGFR of 1.5 mL/min (95% CI 0.5-2.5) if the baseline eGFR was 60-89 mL/min, and 4.1 mL/min (95% CI 1.6-6.6) if <60 mL/min. In contrast, eGFR decreased by 5.8 mL/min (95% CI 2.3-9.3) with the continued use of TDF in individuals with a baseline eGFR <60 mL/min. UPCR decreased after replacing TDF by TAF, independent of baseline eGFR. CONCLUSIONS Switching from TDF to TAF improves eGFR and proteinuria in patients with renal dysfunction.

[1]  P. Volberding,et al.  Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel. , 2020, JAMA.

[2]  A. Vos,et al.  Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV. , 2019, The New England journal of medicine.

[3]  D. Podzamczer,et al.  Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials , 2019, AIDS.

[4]  Huldrych F. Günthard,et al.  Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2018 Recommendations of the International Antiviral Society–USA Panel , 2018, JAMA.

[5]  A. Hill,et al.  Tenofovir alafenamide versus tenofovir disoproxil fumarate: is there a true difference in efficacy and safety? , 2018, Journal of virus eradication.

[6]  S. Swindells,et al.  Plasma and intracellular pharmacokinetics of tenofovir in patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide , 2018, AIDS.

[7]  A. Hill,et al.  Candidates for inclusion in a universal antiretroviral regimen: tenofovir alafenamide , 2017, Current opinion in HIV and AIDS.

[8]  J. Gallant,et al.  Brief Report: Long-Term (96-Week) Efficacy and Safety After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected, Virologically Suppressed Adults , 2017, Journal of acquired immune deficiency syndromes.

[9]  A. LaMarca,et al.  Switching from tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: a randomised, double-blind, multicentre, phase 3b, non-inferiority study. , 2017, The lancet. HIV.

[10]  D. Ward,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. , 2016, The lancet. HIV.

[11]  K. Lichtenstein,et al.  Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study , 2016, Journal of acquired immune deficiency syndromes.

[12]  N. Ford,et al.  Choice of antiretroviral drugs for continued treatment scale-up in a public health approach: what more do we need to know? , 2016, Journal of the International AIDS Society.

[13]  D. Podzamczer,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 , 2015, The Lancet.

[14]  M. Battegay,et al.  The rate of recovery in renal function when patients with HIV infection discontinue treatment with tenofovir , 2014, HIV medicine.

[15]  C. Leen,et al.  Incomplete Reversibility of Estimated Glomerular Filtration Rate Decline Following Tenofovir Disoproxil Fumarate Exposure , 2014, The Journal of infectious diseases.

[16]  S. Piscitelli,et al.  A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects. , 2013, British journal of clinical pharmacology.

[17]  P. German,et al.  Effect of Cobicistat on Glomerular Filtration Rate in Subjects With Normal and Impaired Renal Function , 2012, Journal of acquired immune deficiency syndromes.

[18]  R. Weber,et al.  Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  F. J. López Hernández,et al.  Etiopathology of chronic tubular, glomerular and renovascular nephropathies: Clinical implications , 2011, Journal of Translational Medicine.

[20]  Amalio Telenti,et al.  Cohort profile: the Swiss HIV Cohort study. , 2010, International journal of epidemiology.

[21]  M. Tonelli,et al.  Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  C. Schmid,et al.  A new equation to estimate glomerular filtration rate. , 2009, Annals of internal medicine.

[23]  H. Furrer,et al.  Effect of tenofovir on renal glomerular and tubular function , 2007, AIDS.

[24]  B. Gazzard,et al.  The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years , 2007, AIDS.

[25]  N W Shock,et al.  Longitudinal Studies on the Rate of Decline in Renal Function with Age , 1985, Journal of the American Geriatrics Society.

[26]  P. Sax,et al.  Brief Report: Randomized, Double-Blind Comparison of Tenofovir Alafenamide (TAF) vs Tenofovir Disoproxil Fumarate (TDF), Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine (E/C/F) for Initial HIV-1 Treatment Week 144 Results , 2017, Journal of acquired immune deficiency syndromes.

[27]  J. van Lunzen,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. , 2016, The Lancet. Infectious diseases.

[28]  R. Haubrich,et al.  Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy. , 2008, The Journal of infectious diseases.

[29]  Guidelines for the treatment of HIV. , 1999, Newsline.

[30]  K. Rootwelt,et al.  Renal effects of trimethoprim in ciclosporin- and azathioprine-treated kidney-allografted patients. , 1989, Nephron.

[31]  M. Das,et al.  Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Adults With Renal Impairment: 96-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study , 2022 .