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Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Research Article

Changes in Leptin to Adiponectin Ratio After Antiretroviral Therapy: A Pilot Observational Study

Author(s): Shinichi Hikasa*, Shota Shimabukuro, Kyoko Hideta, Satoshi Higasa, Akihiro Sawada, Tazuko Tokugawa, Kuniyoshi Tanaka, Mina Yanai and Takeshi Kimura

Volume 21, Issue 3, 2023

Published on: 04 August, 2023

Page: [185 - 191] Pages: 7

DOI: 10.2174/1570162X21666230327165902

Price: $65

Abstract

Aim: Weight gain with the use of dolutegravir, bictegravir, and tenofovir alafenamide for antiretroviral therapy has been reported. However, studies on changes in body composition and the leptin/adiponectin ratio after antiretroviral therapy initiation are limited. These factors are important because they can be used as indicators of metabolic syndrome and cardiovascular disease risk.

Introduction: This study aimed to investigate the changes in waist circumference, body composition, and adipokine levels after the initiation of antiretroviral therapy consisting of dolutegravir, bictegravir, and tenofovir alafenamide and evaluate the relationships between these parameters in Japanese patients living with human immunodeficiency virus.

Methods: This is a single-center, prospective, observational study. Waist circumference, body composition, and adipokine levels were measured at baseline and 12 months after antiretroviral therapy initiation in antiretroviral therapy-naive Japanese patients living with human immunodeficiency virus. Body composition was determined by bioelectrical impedance analysis.

Results: We included 11 patients (10 bictegravir/TAF/emtricitabine, 1 dolutegravir/lamivudine) in this study. The results showed no significant changes in waist circumference and body composition among the patients. The leptin/adiponectin ratio and serum leptin levels significantly increased after antiretroviral therapy initiation. Changes in waist circumference, fat mass, and visceral fat area showed a strong positive correlation.

Conclusion: The leptin/adiponectin ratio increased following antiretroviral therapy initiation. The waist circumference measurement can be a simple, inexpensive, and useful method to identify changes in fat mass and visceral fat area after initiation of antiretroviral therapy.

Graphical Abstract

[1]
Palella FJ Jr, Baker RK, Moorman AC, et al. Mortality in the highly active antiretroviral therapy era: Changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr 2006; 43(1): 27-34.
[http://dx.doi.org/10.1097/01.qai.0000233310.90484.16] [PMID: 16878047]
[2]
Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338(13): 853-60.
[http://dx.doi.org/10.1056/NEJM199803263381301] [PMID: 9516219]
[3]
Cruciani M, Parisi SG. Dolutegravir based antiretroviral therapy compared to other combined antiretroviral regimens for the treatment of HIV-infected naive patients: A systematic review and meta-analysis. PLoS One 2019; 14(9): e0222229.
[http://dx.doi.org/10.1371/journal.pone.0222229] [PMID: 31504060]
[4]
Nance RM, Vannappagari V, Smith K, et al. Virologic failure among people living with HIV initiating dolutegravir-based versus other recommended regimens in real-world clinical care settings. J Acquir Immune Defic Syndr 2019; 81(5): 572-7.
[http://dx.doi.org/10.1097/QAI.0000000000002075] [PMID: 31107299]
[5]
Calmy A, Tovar ST, Kouanfack C, et al. Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection (NAMSAL): Week 96 results from a two-group, multicentre, randomised, open label, phase 3 non-inferiority trial in Cameroon. Lancet HIV 2020; 7(10): e677-87.
[http://dx.doi.org/10.1016/S2352-3018(20)30238-1] [PMID: 33010241]
[6]
Nickel K, Halfpenny NJA, Snedecor SJ, Punekar YS. Comparative efficacy, safety and durability of dolutegravir relative to common core agents in treatment-naïve patients infected with HIV-1: An update on a systematic review and network meta-analysis. BMC Infect Dis 2021; 21(1): 222.
[http://dx.doi.org/10.1186/s12879-021-05850-0] [PMID: 33637050]
[7]
Kanters S, Vitoria M, Doherty M, et al. Comparative efficacy and safety of first-line antiretroviral therapy for the treatment of HIV infection: A systematic review and network meta-analysis. Lancet HIV 2016; 3(11): e510-20.
[http://dx.doi.org/10.1016/S2352-3018(16)30091-1] [PMID: 27658869]
[8]
Davy-Mendez T, Eron JJ, Zakharova O, Wohl DA, Napravnik S. Increased persistence of initial treatment for HIV infection with modern antiretroviral therapy. J Acquir Immune Defic Syndr 2017; 76(2): 111-5.
[http://dx.doi.org/10.1097/QAI.0000000000001481] [PMID: 28628528]
[9]
Aloy B, Tazi I, Bagnis CI, et al. Is tenofovir alafenamide safer than tenofovir disoproxil fumarate for the kidneys? AIDS Rev 2016; 18(4): 184-92.
[PMID: 27438578]
[10]
Gibson AK, Shah BM, Nambiar PH, Schafer JJ. Tenofovir alafenamide. Ann Pharmacother 2016; 50(11): 942-52.
[http://dx.doi.org/10.1177/1060028016660812] [PMID: 27465879]
[11]
Hikasa S, Shimabukuro S, Hideta K, et al. Decreased levels of urinary liver-type fatty acid-binding protein after switching from tenofovir disoproxil fumarate to tenofovir alafenamide: A prospective observational study. Int J STD AIDS 2019; 30(13): 1311-7.
[http://dx.doi.org/10.1177/0956462419873772] [PMID: 31726929]
[12]
Schwarze-Zander C, Piduhn H, Boesecke C, 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.
[http://dx.doi.org/10.1111/hiv.12840] [PMID: 32065713]
[13]
Tao X, Lu Y, Zhou Y, Zhang L, Chen Y. Efficacy and safety of the regimens containing tenofovir alafenamide versus tenofovir disoproxil fumarate in fixed-dose single-tablet regimens for initial treatment of HIV-1 infection: A meta-analysis of randomized controlled trials. Int J Infect Dis 2020; 93: 108-17.
[http://dx.doi.org/10.1016/j.ijid.2020.01.035] [PMID: 31988012]
[14]
Bailin SS, Gabriel CL, Wanjalla CN, Koethe JR. Obesity and weight gain in persons with HIV. Curr HIV/AIDS Rep 2020; 17(2): 138-50.
[http://dx.doi.org/10.1007/s11904-020-00483-5] [PMID: 32072466]
[15]
Lake JE, Trevillyan J. Impact of integrase inhibitors and tenofovir alafenamide on weight gain in people with HIV. Curr Opin HIV AIDS 2021; 16(3): 148-51.
[http://dx.doi.org/10.1097/COH.0000000000000680] [PMID: 33797433]
[16]
Shah S, Hindley L, Hill A. Are new antiretroviral treatments increasing the risk of weight gain? Drugs 2021; 81(3): 299-315.
[http://dx.doi.org/10.1007/s40265-020-01457-y] [PMID: 33400239]
[17]
Wood BR, Huhn GD. Excess weight gain with integrase inhibitors and tenofovir alafenamide: What is the mechanism and does it matter? Open Forum Infect Dis 2021; 8(12): ofab542.
[http://dx.doi.org/10.1093/ofid/ofab542] [PMID: 34877366]
[18]
Galdamez R, García JA, Fernández M, et al. Short-term increase in risk of overweight and concomitant systolic blood pressure elevation in treatment-naïve persons starting INSTI-based antiretroviral therapy. Open Forum Infect Dis 2019; 6(12): ofz491.
[http://dx.doi.org/10.1093/ofid/ofz491] [PMID: 32128334]
[19]
McCann K, Shah S, Hindley L, et al. Implications of weight gain with newer anti-retrovirals: 10-year predictions of cardiovascular disease and diabetes. AIDS 2021; 35(10): 1657-65.
[PMID: 33927086]
[20]
Nolan NS, Adamson S, Reeds D, O’Halloran JA. Bictegravir-based antiretroviral therapy-associated accelerated hyperglycemia and diabetes mellitus. Open Forum Infect Dis 2021; 8(5): ofab077.
[http://dx.doi.org/10.1093/ofid/ofab077] [PMID: 33981777]
[21]
Rebeiro PF, Jenkins CA, Bian A, et al. Risk of incident diabetes mellitus, weight gain, and their relationships with integrase inhibitor-based initial antiretroviral therapy among persons with human immunodeficiency virus in the United States and Canada. Clin Infect Dis 2021; 73(7): e2234-42.
[http://dx.doi.org/10.1093/cid/ciaa1403] [PMID: 32936919]
[22]
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.
[http://dx.doi.org/10.1093/ofid/ofz414] [PMID: 31660372]
[23]
Venter WDF, Sokhela S, Simmons B, et al. Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): Week 96 results from a randomised, phase 3, non-inferiority trial. Lancet HIV 2020; 7(10): e666-76.
[http://dx.doi.org/10.1016/S2352-3018(20)30241-1] [PMID: 33010240]
[24]
Wan CS, Ward LC, Halim J, et al. Bioelectrical impedance analysis to estimate body composition, and change in adiposity, in overweight and obese adolescents: Comparison with dual-energy x-ray absorptiometry. BMC Pediatr 2014; 14(1): 249.
[http://dx.doi.org/10.1186/1471-2431-14-249] [PMID: 25280868]
[25]
Di Angelantonio E, Bhupathiraju SN, Wormser D, et al. Body-mass index and all-cause mortality: Individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet 2016; 388(10046): 776-86.
[http://dx.doi.org/10.1016/S0140-6736(16)30175-1] [PMID: 27423262]
[26]
Kivimäki M, Kuosma E, Ferrie JE, et al. Overweight, obesity, and risk of cardiometabolic multimorbidity: Pooled analysis of individual-level data for 120 813 adults from 16 cohort studies from the USA and Europe. Lancet Public Health 2017; 2(6): e277-85.
[http://dx.doi.org/10.1016/S2468-2667(17)30074-9] [PMID: 28626830]
[27]
Sahakyan KR, Somers VK, Rodriguez-Escudero JP, et al. Normal-weight central obesity: Implications for total and cardiovascular mortality. Ann Intern Med 2015; 163(11): 827-35.
[http://dx.doi.org/10.7326/M14-2525] [PMID: 26551006]
[28]
Lee DH, Keum N, Hu FB, et al. Predicted lean body mass, fat mass, and all cause and cause specific mortality in men: Prospective US cohort study. BMJ 2018; 362: k2575.
[http://dx.doi.org/10.1136/bmj.k2575] [PMID: 29970408]
[29]
McComsey GA, Moser C, Currier J, et al. Body composition changes after initiation of raltegravir or protease inhibitors: ACTG A5260s. Clin Infect Dis 2016; 62(7): 853-62.
[http://dx.doi.org/10.1093/cid/ciw017] [PMID: 26797215]
[30]
Venter WDF, Moorhouse M, Sokhela S, et al. Dolutegravir plus two different prodrugs of tenofovir to treat HIV. N Engl J Med 2019; 381(9): 803-15.
[http://dx.doi.org/10.1056/NEJMoa1902824] [PMID: 31339677]
[31]
Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334(5): 292-5.
[http://dx.doi.org/10.1056/NEJM199602013340503] [PMID: 8532024]
[32]
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372(6505): 425-32.
[http://dx.doi.org/10.1038/372425a0] [PMID: 7984236]
[33]
Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 2004; 145(5): 2273-82.
[http://dx.doi.org/10.1210/en.2003-1336] [PMID: 14726444]
[34]
Couillard C, Mauriège P, Imbeault P, et al. Hyperleptinemia is more closely associated with adipose cell hypertrophy than with adipose tissue hyperplasia. Int J Obes 2000; 24(6): 782-8.
[http://dx.doi.org/10.1038/sj.ijo.0801227] [PMID: 10878687]
[35]
Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 2007; 92(3): 1023-33.
[http://dx.doi.org/10.1210/jc.2006-1055] [PMID: 17164304]
[36]
Bruun JM, Lihn AS, Verdich C, et al. Regulation of adiponectin by adipose tissue-derived cytokines: In vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab 2003; 285(3): E527-33.
[http://dx.doi.org/10.1152/ajpendo.00110.2003] [PMID: 12736161]
[37]
Kappelle PJWH, Dullaart RPF, van Beek AP, Hillege HL, Wolffenbuttel BHR. The plasma leptin/adiponectin ratio predicts first cardiovascular event in men: A prospective nested case–control study. Eur J Intern Med 2012; 23(8): 755-9.
[http://dx.doi.org/10.1016/j.ejim.2012.06.013] [PMID: 22819464]
[38]
Kotani K, Sakane N, Saiga K, Kurozawa Y. Leptin: Adiponectin ratio as an atherosclerotic index in patients with type 2 diabetes: Relationship of the index to carotid intima–media thickness. Diabetologia 2005; 48(12): 2684-6.
[http://dx.doi.org/10.1007/s00125-005-0015-4] [PMID: 16261311]
[39]
Nguyen PAH, Heggermont WA, Vanhaverbeke M, et al. Leptin-adiponectin ratio in pre-diabetic patients undergoing percutaneous coronary intervention. Acta Cardiol 2015; 70(6): 640-6.
[http://dx.doi.org/10.1080/AC.70.6.3120175] [PMID: 26717211]
[40]
Norata GD, Raselli S, Grigore L, et al. Leptin:Adiponectin ratio is an independent predictor of intima media thickness of the common carotid artery. Stroke 2007; 38(10): 2844-6.
[http://dx.doi.org/10.1161/STROKEAHA.107.485540] [PMID: 17823381]
[41]
Satoh N, Naruse M, Usui T, et al. Leptin-to-adiponectin ratio as a potential atherogenic index in obese type 2 diabetic patients. Diabetes Care 2004; 27(10): 2488-90.
[http://dx.doi.org/10.2337/diacare.27.10.2488] [PMID: 15451921]
[42]
Takamura N, Hayashida N, Hagane K, et al. Leptin to high-molecular-weight adiponectin ratio is independently correlated with carotid intima-media thickness in men, but not in women. Biomarkers 2010; 15(4): 340-4.
[http://dx.doi.org/10.3109/13547501003735532] [PMID: 20345321]
[43]
Koethe JR, Moser C, Brown TT, et al. Adipokines, weight gain and metabolic and inflammatory markers after antiretroviral therapy initiation: AIDS Clinical Trials Group (ACTG) A5260s. Clin Infect Dis 2022; 74(5): 857-64.
[http://dx.doi.org/10.1093/cid/ciab542] [PMID: 34117756]
[44]
Sinha MK, Ohannesian JP, Heiman ML, et al. Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest 1996; 97(5): 1344-7.
[http://dx.doi.org/10.1172/JCI118551] [PMID: 8636448]
[45]
Gavrila A, Peng CK, Chan JL, Mietus JE, Goldberger AL, Mantzoros CS. Diurnal and ultradian dynamics of serum adiponectin in healthy men: Comparison with leptin, circulating soluble leptin receptor, and cortisol patterns. J Clin Endocrinol Metab 2003; 88(6): 2838-43.
[http://dx.doi.org/10.1210/jc.2002-021721] [PMID: 12788897]
[46]
Ashwell M, Hsieh SD. Six reasons why the waist-to-height ratio is a rapid and effective global indicator for health risks of obesity and how its use could simplify the international public health message on obesity. Int J Food Sci Nutr 2005; 56(5): 303-7.
[http://dx.doi.org/10.1080/09637480500195066] [PMID: 16236591]
[47]
Craig CL, Marshall AL, Sjöström M, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 2003; 35(8): 1381-95.
[http://dx.doi.org/10.1249/01.MSS.0000078924.61453.FB] [PMID: 12900694]
[48]
Murase N. Validity and reliability of japanese version of international physical activity questionnaire. J Health Welfare Stat 2002; 49(11): 1-9.
[49]
Van Harmelen V, Reynisdottir S, Eriksson P, et al. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes 1998; 47(6): 913-7.
[http://dx.doi.org/10.2337/diabetes.47.6.913] [PMID: 9604868]
[50]
Park KG, Park KS, Kim MJ, et al. Relationship between serum adiponectin and leptin concentrations and body fat distribution. Diabetes Res Clin Pract 2004; 63(2): 135-42.
[http://dx.doi.org/10.1016/j.diabres.2003.09.010] [PMID: 14739054]
[51]
Shrivastav S, Kino T, Cunningham T, et al. Human immunodeficiency virus (HIV)-1 viral protein R suppresses transcriptional activity of peroxisome proliferator-activated receptor γ and inhibits adipocyte differentiation: Implications for HIV-associated lipodystrophy. Mol Endocrinol 2008; 22(2): 234-47.
[http://dx.doi.org/10.1210/me.2007-0124] [PMID: 17932108]
[52]
Díaz-Delfín J, Domingo P, Mateo MG, et al. Effects of rilpivirine on human adipocyte differentiation, gene expression, and release of adipokines and cytokines. Antimicrob Agents Chemother 2012; 56(6): 3369-75.
[http://dx.doi.org/10.1128/AAC.00104-12] [PMID: 22430974]
[53]
Domingo P, Quesada-López T, Villarroya J, et al. Differential effects of dolutegravir, bictegravir and raltegravir in adipokines and inflammation markers on human adipocytes. Life Sci 2022; 308(120948): 120948.
[http://dx.doi.org/10.1016/j.lfs.2022.120948] [PMID: 36096241]

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