Lipid profile after switching from a TDF (tenofovir disoproxil)-containing to TAF (tenofovir alafenamide)-containing regimen in virologically suppressed people living with HIV
DOI:
https://doi.org/10.20883/medical.e808Keywords:
antiretroviral therapy, tenofovir disoproxil fumarate, tenofovir alafenamide, lipids, cholesterol, low-density lipoproteinsAbstract
Background. Tenofovir disoproxil fumarate (TDF) or its prodrug, tenofovir alafenamide fumarate (TAF), is currently being recommended in treatment of HIV infection. The distinct pharmacological properties of these two forms of this drug make TAF treatment less nephrotoxic and lead to a better impact on bone density. Nevertheless, a rising concern about TAF's possible metabolic adverse effects exists. This study aimed to evaluate the effects on the lipid profile among ART (antiretroviral therapy) patients switching from a TDF-containing to a TAF-containing regimen in the first year after the switch.
Methods. Demographic and clinical data of HIV-positive ART-experienced patients treated in the infectious diseases department was retrospectively collected. Lipid profile change concerning baseline BMI, age, and time of ART duration were analysed.
Results. In the group of 36 patients, there was a significant increase in total cholesterol levels (+18.43mg/dl, SD=23.86mg/dl, p<0.0001) and LDL levels (+13.75mg/dl, SD=23.05mg/dl, p=0.001) in the first 12 months after switching from a TDF-containing to a TAF-containing regimen. There were no statistically significant changes in both HDL and TG levels observed. Analysis of total cholesterol and LDL levels in specific subpopulations revealed a significant increase within the first year after the switch in patients younger than 40 years old and in those whose BMI was within the normal range.
Conclusions. The 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.
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References
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 Jan;19(1):45-54. doi: 10.1038/s41577-018-0085-4.
Marcus JL, Leyden WA, Alexeeff SE, Anderson AN, Hechter RC, Hu H, Lam JO, Towner WJ, Yuan Q, Horberg MA, Silverberg MJ. Comparison of Overall and Comorbidity-Free Life Expectancy Between Insured Adults With and Without HIV Infection, 2000-2016. JAMA Netw Open. 2020 Jun 1;3(6):e207954. doi: 10.1001/jamanetworkopen.2020.7954.
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 Apr;18(4):256-266. doi: 10.1111/hiv.12421. Epub 2016 Aug 31.
Atta MG, De Seigneux S, Lucas GM. Clinical Pharmacology in HIV Therapy. Clin J Am Soc Nephrol. 2019 Mar 7;14(3):435-444. doi: 10.2215/CJN.02240218. Epub 2018 May 29.
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 Jul;92(7):2506-12. doi: 10.1210/jc.2006-2190. Epub 2007 Apr 24.
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):85-89. doi:10.5114/hivar.2021.107234.
Ryom L, De Miguel R, Cotter AG, Podlekareva D, Beguelin C, Waalewijn H, Arribas JR, Mallon PWG, Marzolini C, Kirk O, Bamford A, Rauch A, Molina JM, Kowalska JD, Guaraldi G, Winston A, Boesecke C, Cinque P, Welch S, Collins S, Behrens GMN; EACS Governing Board. Major revision version 11.0 of the European AIDS Clinical Society Guidelines 2021. HIV Med. 2022 Sep;23(8):849-858. doi: 10.1111/hiv.13268. Epub 2022 Mar 25.
Sax PE, Wohl D, Yin MT, Post F, DeJesus E, Saag M, Pozniak A, Thompson M, Podzamczer D, Molina JM, Oka S, Koenig E, Trottier B, Andrade-Villanueva J, Crofoot G, Custodio JM, Plummer A, Zhong L, Cao H, Martin H, Callebaut C, Cheng AK, Fordyce MW, McCallister S; GS-US-292-0104/0111 Study Team. 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 Jun 27;385(9987):2606-15. doi: 10.1016/S0140-6736(15)60616-X. Epub 2015 Apr 15. Erratum in: Lancet. 2016 Apr 30;387(10030):1816.
Mayer KH, Molina JM, Thompson MA, Anderson PL, Mounzer KC, De Wet JJ, DeJesus E, Jessen H, Grant RM, Ruane PJ, Wong P, Ebrahimi R, Zhong L, Mathias A, Callebaut C, Collins SE, Das M, McCallister S, Brainard DM, Brinson C, Clarke A, Coll P, Post FA, Hare CB. 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 Jul 25;396(10246):239-254. doi: 10.1016/S0140-6736(20)31065-5.
Ruane PJ, DeJesus E, Berger D, Markowitz M, Bredeek UF, Callebaut C, Zhong L, Ramanathan S, Rhee MS, Fordyce MW, Yale K. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of tenofovir alafenamide as 10-day monotherapy in HIV-1-positive adults. J Acquir Immune Defic Syndr. 2013 Aug 1;63(4):449-55. doi: 10.1097/QAI.0b013e3182965d45.
Lee WA, He GX, Eisenberg E, Cihlar T, Swaminathan S, Mulato A, Cundy KC. 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 May;49(5):1898-906. doi: 10.1128/AAC.49.5.1898-1906.2005.
Di Perri G. Tenofovir alafenamide (TAF) clinical pharmacology. Infez Med. 2021 Dec 10;29(4):526-529. doi: 10.53854/liim-2904-4.
Di Perri G. Tenofovir alafenamide revisited. Infez Med. 2020 Dec 1;28(4):525-533. PMID: 33257626.
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 Oct 4;6(10):ofz414. doi: 10.1093/ofid/ofz414.
So-Armah K, Benjamin LA, Bloomfield GS, Feinstein MJ, Hsue P, Njuguna B, Freiberg MS. HIV and cardiovascular disease. Lancet HIV. 2020 Apr;7(4):e279-e293. doi: 10.1016/S2352-3018(20)30036-9.
Shah ASV, Stelzle D, Lee KK, Beck EJ, Alam S, Clifford S, Longenecker CT, Strachan F, Bagchi S, Whiteley W, Rajagopalan S, Kottilil S, Nair H, Newby DE, McAllister DA, Mills NL. Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV: Systematic Review and Meta-Analysis. Circulation. 2018 Sep 11;138(11):1100-1112. doi: 10.1161/CIRCULATIONAHA.117.033369.
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 May;32(6):570-577. doi: 10.1177/0956462420983699.
Shah S, Hill A. Risks of metabolic syndrome and diabetes with integrase inhibitor-based therapy. Curr Opin Infect Dis. 2021 Feb 1;34(1):16-24. doi: 10.1097/QCO.0000000000000695.
Ammirati E, Moroni F, Magnoni M, Camici PG. The role of T and B cells in human atherosclerosis and atherothrombosis. Clin Exp Immunol. 2015 Feb;179(2):173-87. doi: 10.1111/cei.12477.
Abdullah SM, Defina LF, Leonard D, Barlow CE, Radford NB, Willis BL, Rohatgi A, McGuire DK, de Lemos JA, Grundy SM, Berry JD, Khera A. Long-Term Association of Low-Density Lipoprotein Cholesterol With Cardiovascular Mortality in Individuals at Low 10-Year Risk of Atherosclerotic Cardiovascular Disease. Circulation. 2018 Nov 20;138(21):2315-2325. doi: 10.1161/CIRCULATIONAHA.118.034273.
Cid-Silva P, Fernández-Bargiela N, Margusino-Framiñán L, Balboa-Barreiro V, Mena-De-Cea Á, López-Calvo S, Vázquez-Rodríguez P, Martín-Herranz I, Míguez-Rey E, Poveda E, Castro-Iglesias Á. 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 Apr;124(4):479-490. doi: 10.1111/bcpt.13161.
Hagins D, Orkin C, Daar ES, Mills A, Brinson C, DeJesus E, Post FA, Morales-Ramirez J, Thompson M, Osiyemi O, Rashbaum B, Stellbrink HJ, Martorell C, Liu H, Liu YP, Porter D, Collins SE, SenGupta D, Das M. 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 Nov;19(10):724-733. doi: 10.1111/hiv.12664. Epub 2018 Aug 12.
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 Dec;33(12):500-506. doi: 10.1089/apc.2019.0236. Epub 2019 Nov 19.
Lacey A, Savinelli S, Barco EA, Macken A, Cotter AG, Sheehan G, Lambert JS, Muldoon E, Feeney E, Mallon PW, Tinago W; UCD ID Cohort Study. Investigating the effect of antiretroviral switch to tenofovir alafenamide on lipid profiles in people living with HIV. AIDS. 2020 Jul 1;34(8):1161-1170. doi: 10.1097/QAD.0000000000002541.
Schwarze-Zander C, Piduhn H, Boesecke C, Schlabe S, Stoffel-Wagner B, Wasmuth JC, Strassburg CP, Rockstroh JK. Switching tenofovir disoproxil fumarate to tenofovir alafenamide in a real life setting: what are the implications? HIV Med. 2020 Jul;21(6):378-385. doi: 10.1111/hiv.12840. Epub 2020 Feb 17.
Huhn GD, Shamblaw DJ, Baril JG, Hsue PY, Mills BL, Nguyen-Cleary T, McCallister S, Das M. Atherosclerotic Cardiovascular Disease Risk Profile of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate. Open Forum Infect Dis. 2019 Nov 11;7(1):ofz472. doi: 10.1093/ofid/ofz472.
Taramasso L, Di Biagio A, Riccardi N, Briano F, Di Filippo E, Comi L, Mora S, Giacomini M, Gori A, Maggiolo F. 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 Oct 11;14(10):e0223181. doi: 10.1371/journal.pone.0223181.
Lemieux I, Lamarche B, Couillard C, Pascot A, Cantin B, Bergeron J, Dagenais GR, Després JP. 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 Dec 10-24;161(22):2685-92. doi: 10.1001/archinte.161.22.2685.
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 Dec 1;33(15):2387-2391. doi: 10.1097/QAD.0000000000002350.
Santos JR, Saumoy M, Curran A, Bravo I, Llibre JM, Navarro J, Estany C, Podzamczer D, Ribera E, Negredo E, Clotet B, Paredes R; Tenofovir/emtricitabine inflUence on LIPid metabolism (TULIP) Study Group. The lipid-lowering effect of tenofovir/emtricitabine: a randomized, crossover, double-blind, placebo-controlled trial. Clin Infect Dis. 2015 Aug 1;61(3):403-8. doi: 10.1093/cid/civ296. Epub 2015 Apr 13.
Orkaby AR, Driver JA, Ho YL, Lu B, Costa L, Honerlaw J, Galloway A, Vassy JL, Forman DE, Gaziano JM, Gagnon DR, Wilson PWF, Cho K, Djousse L. Association of Statin Use With All-Cause and Cardiovascular Mortality in US Veterans 75 Years and Older. JAMA. 2020 Jul 7;324(1):68-78. doi: 10.1001/jama.2020.7848. Erratum in: JAMA. 2020 Oct 13;324(14):1468.
Lim J, Choi WM, Shim JH, Lee D, Kim KM, Lim YS, Lee HC, Choi J. Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in treatment-naïve chronic hepatitis B. Liver Int. 2022 Jul;42(7):1517-1527. doi: 10.1111/liv.15261. Epub 2022 Apr 3.
Glidden DV, Mulligan K, McMahan V, Anderson PL, Guanira J, Chariyalertsak S, Buchbinder SP, Bekker LG, Schechter M, Grinsztejn B, Grant RM. Metabolic Effects of Preexposure Prophylaxis With Coformulated Tenofovir Disoproxil Fumarate and Emtricitabine. Clin Infect Dis. 2018 Jul 18;67(3):411-419. doi: 10.1093/cid/ciy083.
Blackman AL, Pandit NS, Pincus KJ. Comparing rates of statin therapy in eligible patients living with HIV versus uninfected patients. HIV Med. 2020 Mar;21(3):135-141. doi: 10.1111/hiv.12794. Epub 2019 Dec 25.
Pincus KJ, Blackman AL, Suen SY, Devabhakthuni S, Gale S, Noel ZR, Seung H, Pandit NS. Statin gap in patients living with HIV: assessing dose appropriateness. HIV Med. 2021 Nov;22(10):917-923. doi: 10.1111/hiv.13150. Epub 2021 Aug 8.
Gallegos Aragon K, Ray G, Conklin J, Stever E, Marquez C, Magallanes A, Anderson J, Jakeman B. Underprescribing of statin therapy in people with HIV at risk for atherosclerotic cardiovascular disease. Am J Health Syst Pharm. 2022 Nov 7;79(22):2026-2031. doi: 10.1093/ajhp/zxac224.
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 Apr;7(4):457-77. doi: 10.1517/17425255.2011.558839. Epub 2011 Feb 23.
Maggi P, Di Biagio A, Rusconi S, Cicalini S, D'Abbraccio M, d'Ettorre G, Martinelli C, Nunnari G, Sighinolfi L, Spagnuolo V, Squillace N. Cardiovascular risk and dyslipidemia among persons living with HIV: a review. BMC Infect Dis. 2017 Aug 9;17(1):551. doi: 10.1186/s12879-017-2626-z.
Gazzola L, Tagliaferri G, De Bona A, Mondatore D, Borsino C, Bini T, Marchetti G, d'Arminio Monforte A. Dyslipidaemia after switch to tenofovir alafenamide (TAF)-based cART regimens in a cohort of HIV-positive patients: what clinical relevance? HIV Med. 2021 Feb;22(2):140-145. doi: 10.1111/hiv.12984. Epub 2020 Oct 21.
Squillace N, Ricci E, Menzaghi B, De Socio GV, Passerini S, Martinelli C, Mameli MS, Maggi P, Falasca K, Cordier L, Celesia BM, Salomoni E, Di Biagio A, Pellicanò GF, Bonfanti P; CISAI Study Group. 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 Dec 15;14:5515-5520. doi: 10.2147/DDDT.S274307.
Brunet L, Mallon P, Fusco JS, Wohlfeiler MB, Prajapati G, Beyer A, Fusco GP. Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living with HIV: Lipid Changes and Statin Underutilization. Clin Drug Investig. 2021 Nov;41(11):955-965. doi: 10.1007/s40261-021-01081-y. Epub 2021 Sep 21.
Plum PE, Maes N, Sauvage AS, Frippiat F, Meuris C, Uurlings F, Lecomte M, Léonard P, Paquot N, Fombellida K, Vaira D, Moutschen M, Darcis G. 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 Sep 6;21(1):910. doi: 10.1186/s12879-021-06479-9.
Kanda N, Okamoto K, Okumura H, Mieno M, Sakashita K, Sasahara T, Hatakeyama S. 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 Jul;22(6):457-466. doi: 10.1111/hiv.13061. Epub 2021 Mar 15.
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Accepted 2023-07-19
Published 2023-09-26