Lipid profile after switching from TDF (tenofovir disoproxil)-containing to TAF (tenofovir alafenamide)-containing regimen in virologically suppressed people living with HIV
Keywords:antiretroviral therapy, tenofovir disoproxil fumarate, tenofovir alafenamide, lipids, cholesterol, low-density lipoproteins
Background. Tenofovir disoproxil fumarate (TDF) or its prodrug tenofovir alafenamide fumarate (TAF) are currently being recommended in treatment of HIV infection. Distinct pharmacological properties of these two forms of a this drug make TAF treatment less nephrotoxic and lead to better impact on bone density. Nevertheless, there is a rising concern about possible metabolic adverse effects of TAF. The purpose of this study was to evaluate the effects on the lipid profile among ART (antiretroviral therapy)-experienced patients switching from TDF‑containing to TAF‑containing regimen in the first year after the switch.
Methods. Demographic and clinical data of HIV‑positive ART‑experienced patients treated in infectious diseases department was retrospectively collected. Changes of lipid profile with regards to baseline BMI, age and time of ART duration were analyzed.
Results. In the group of 36 patients there was a significant increase in total cholesterol levels (+18.43 mg/dl, SD = 23.86 mg/dl, p < 0.0001) and LDL levels (+13.75 mg/dl SD = 23.05 mg/dl, p = 0.001) in first 12 months after switching from TDF‑containing to TAF‑containing regimen. There were no statistically significant changes in both HDL and TG levels observed. Analysis of total cholesterol and LDL levels in certain subpopulations revealed a significant increase within first year after the switch in patients younger than 40 years old and in those whose BMI was within normal range.
Conclusions. Presented data suggests that switching from TDF to TAF in ART‑experienced patients may be associated with worsening lipid parameters. Early detection and management of dyslipidemias among HIV‑positive patients are needed.
Davenport MP, Khoury DS, Cromer D, Lewin SR, Kelleher AD, Kent SJ. Functional cure of HIV: the scale of the challenge. Nat Rev Immunol. 2019;19(1):45-54.
Marcus JL, Leyden WA, Alexeeff SE, Anderson AN, Hechter RC, Hu H, et al. Comparison of Overall and Comorbidity-Free Life Expectancy Between Insured Adults With and Without HIV Infection, 2000-2016. JAMA Netw Open. 2020;3(6):e207954.
Teeraananchai S, Kerr SJ, Amin J, Ruxrungtham K, Law MG. Life expectancy of HIV-positive people after starting combination antiretroviral therapy: a meta-analysis. HIV Med. 2017;18(4):256-66.
Atta MG, De Seigneux S, Lucas GM. Clinical Pharmacology in HIV Therapy. Clin J Am Soc Nephrol. 2019;14(3):435-44.
Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007;92(7):2506-12.
Jachymek M, Braksator M, Parczewski M, Peregud-Pogorzelska M, Kaźmierczak J. Cardiovascular disease and HIV infection. HIV & AIDS Review International Journal of HIV-Related Problems. 2021;20(2):85-9.
European AIDS Clinical Society Guidelines. October 2021;version 11.0
Sax PE, Wohl D, Yin MT, Post F, DeJesus E, Saag M, 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(9987):2606-15.
Mayer KH, Molina JM, Thompson MA, Anderson PL, Mounzer KC, De Wet JJ, et al. Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet. 2020;396(10246):239-54.
Ruane PJ, DeJesus E, Berger D, Markowitz M, Bredeek UF, Callebaut C, et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of tenofovir alafenamide as 10-day monotherapy in HIV-1-positive adults. J Acquir Immune Defic Syndr. 2013;63(4):449-55.
Lee WA, He GX, Eisenberg E, Cihlar T, Swaminathan S, Mulato A, 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(5):1898-906.
Di Perri G. Tenofovir alafenamide (TAF) clinical pharmacology. Infez Med. 2021;29(4):526-9.
Di Perri G. Tenofovir alafenamide revisited. Infez Med. 2020;28(4):525-33.
Schafer JJ, Sassa KN, O’Connor JR, Shimada A, Keith SW, DeSimone JA. Changes in Body Mass Index and Atherosclerotic Disease Risk Score After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide. Open Forum Infect Dis. 2019;6(10):ofz414.
So-Armah K, Benjamin LA, Bloomfield GS, Feinstein MJ, Hsue P, Njuguna B, et al. HIV and cardiovascular disease. Lancet HIV. 2020;7(4):e279-e93.
Shah ASV, Stelzle D, Lee KK, Beck EJ, Alam S, Clifford S, et al. Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV: Systematic Review and Meta-Analysis. Circulation. 2018;138(11):1100-12.
Łomiak M, Stępnicki J, Mikuła T, Wiercińska-Drapało A. Weight and body mass index increase after switch from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate-containing treatment in an antiretroviral therapy-experienced group. Int J STD AIDS. 2021;32(6):570-7.
Shah S, Hill A. Risks of metabolic syndrome and diabetes with integrase inhibitor-based therapy. Curr Opin Infect Dis. 2021;34(1):16-24.
Ammirati E, Moroni F, Magnoni M, Camici PG. The role of T and B cells in human atherosclerosis and atherothrombosis. Clin Exp Immunol. 2015;179(2):173-87.
Abdullah SM, Defina LF, Leonard D, Barlow CE, Radford NB, Willis BL, et al. Long-Term Association of Low-Density Lipoprotein Cholesterol With Cardiovascular Mortality in Individuals at Low 10-Year Risk of Atherosclerotic Cardiovascular Disease. Circulation. 2018;138(21):2315-25.
Cid-Silva P, Fernández-Bargiela N, Margusino-Framiñán L, Balboa-Barreiro V, Mena-De-Cea Á, López-Calvo S, et al. Treatment with tenofovir alafenamide fumarate worsens the lipid profile of HIV-infected patients versus treatment with tenofovir disoproxil fumarate, each coformulated with elvitegravir, cobicistat, and emtricitabine. Basic Clin Pharmacol Toxicol. 2019;124(4):479-90.
Hagins D, Orkin C, Daar ES, Mills A, Brinson C, DeJesus E, et al. Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96-week results from two randomized clinical trials. HIV Med. 2018;19(10):724-33.
Kauppinen KJ, Kivelä P, Sutinen J. Switching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide Significantly Worsens the Lipid Profile in a Real-World Setting. AIDS Patient Care STDS. 2019;33(12):500-6.
Lacey A, Savinelli S, Barco EA, Macken A, Cotter AG, Sheehan G, et al. Investigating the effect of antiretroviral switch to tenofovir alafenamide on lipid profiles in people living with HIV. Aids. 2020;34(8):1161-70.
Schwarze-Zander C, Piduhn H, Boesecke C, Schlabe S, Stoffel-Wagner B, Wasmuth JC, et al. Switching tenofovir disoproxil fumarate to tenofovir alafenamide in a real life setting: what are the implications? HIV Med. 2020;21(6):378-85.
Huhn GD, Shamblaw DJ, Baril JG, Hsue PY, Mills BL, Nguyen-Cleary T, et al. Atherosclerotic Cardiovascular Disease Risk Profile of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate. Open Forum Infect Dis. 2020;7(1):ofz472.
Taramasso L, Di Biagio A, Riccardi N, Briano F, Di Filippo E, Comi L, et al. Lipid profile changings after switching from rilpivirine/tenofovir disoproxil fumarate/emtricitabine to rilpivirine/tenofovir alafenamide/emtricitabine: Different effects in patients with or without baseline hypercholesterolemia. PLoS One. 2019;14(10):e0223181.
Lemieux I, Lamarche B, Couillard C, Pascot A, Cantin B, Bergeron J, et al. Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study. Arch Intern Med. 2001;161(22):2685-92.
Milinkovic A, Berger F, Arenas-Pinto A, Mauss S. Reversible effect on lipids by switching from tenofovir disoproxil fumarate to tenofovir alafenamide and back. Aids. 2019;33(15):2387-91.
Santos JR, Saumoy M, Curran A, Bravo I, Llibre JM, Navarro J, et al. The lipid-lowering effect of tenofovir/emtricitabine: a randomized, crossover, double-blind, placebo-controlled trial. Clin Infect Dis. 2015;61(3):403-8.
Orkaby AR, Driver JA, Ho YL, Lu B, Costa L, Honerlaw J, et al. Association of Statin Use With All-Cause and Cardiovascular Mortality in US Veterans 75 Years and Older. Jama. 2020;324(1):68-78.
Lim J, Choi WM, Shim JH, Lee D, Kim KM, Lim YS, et al. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in treatment-naïve chronic hepatitis B. Liver international : official journal of the International Association for the Study of the Liver. 2022;42(7):1517-27.
Glidden DV, Mulligan K, McMahan V, Anderson PL, Guanira J, Chariyalertsak S, et al. Metabolic Effects of Preexposure Prophylaxis With Coformulated Tenofovir Disoproxil Fumarate and Emtricitabine. Clin Infect Dis. 2018;67(3):411-9.
Blackman AL, Pandit NS, Pincus KJ. Comparing rates of statin therapy in eligible patients living with HIV versus uninfected patients. HIV Med. 2020;21(3):135-41.
Pincus KJ, Blackman AL, Suen SY, Devabhakthuni S, Gale S, Noel ZR, et al. Statin gap in patients living with HIV: assessing dose appropriateness. HIV Med. 2021;22(10):917-23.
Aragon KG, Ray G, Conklin J, Stever E, Marquez C, Magallanes A, et al. Underprescribing of statin therapy in people with HIV at risk for atherosclerotic cardiovascular disease. Am J Health Syst Pharm. 2022.
Jiménez-Nácher I, Alvarez E, Morello J, Rodriguez-Nóvoa S, de Andrés S, Soriano V. Approaches for understanding and predicting drug interactions in human immunodeficiency virus-infected patients. Expert Opin Drug Metab Toxicol. 2011;7(4):457-77.
Maggi P, Di Biagio A, Rusconi S, Cicalini S, D’Abbraccio M, d’Ettorre G, et al. Cardiovascular risk and dyslipidemia among persons living with HIV: a review. BMC Infect Dis. 2017;17(1):551.
Gazzola L, Tagliaferri G, De Bona A, Mondatore D, Borsino C, Bini T, et al. Dyslipidaemia after switch to tenofovir alafenamide (TAF)-based cART regimens in a cohort of HIV-positive patients: what clinical relevance? HIV Med. 2021;22(2):140-5.
Squillace N, Ricci E, Menzaghi B, De Socio GV, Passerini S, Martinelli C, et al. The Effect of Switching from Tenofovir Disoproxil Fumarate (TDF) to Tenofovir Alafenamide (TAF) on Liver Enzymes, Glucose, and Lipid Profile. Drug Des Devel Ther. 2020;14:5515-20.
Brunet L, Mallon P, Fusco JS, Wohlfeiler MB, Prajapati G, Beyer A, et al. Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living with HIV: Lipid Changes and Statin Underutilization. Clin Drug Investig. 2021;41(11):955-65.
Plum PE, Maes N, Sauvage AS, Frippiat F, Meuris C, Uurlings F, et al. Impact of switch from tenofovir disoproxil fumarate-based regimens to tenofovir alafenamide-based regimens on lipid profile, weight gain and cardiovascular risk score in people living with HIV. BMC Infect Dis. 2021;21(1):910.
Kanda N, Okamoto K, Okumura H, Mieno M, Sakashita K, Sasahara T, et al. Outcomes associated with treatment change from tenofovir disoproxil fumarate to tenofovir alafenamide in HIV-1-infected patients: a real-world study in Japan. HIV Med. 2021;22(6):457-66.
How to Cite
Copyright (c) 2023 The copyright to the submitted manuscript is held by the Author, who grants the Journal of Medical Science (JMS) a nonexclusive licence to use, reproduce, and distribute the work, including for commercial purposes.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.