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The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection

  • Complications of Antiretroviral Therapy (G McComsey, Section Editor)
  • Published:
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Abstract

Purpose of Review

The aim of this review is to summarize knowledge of the prevalence, relevant physiology, and consequences of obesity and visceral adiposity in HIV-infected adults, including highlighting gaps in current knowledge and future research directions.

Recent Findings

Similar to the general population, obesity prevalence is increasing among HIV-infected persons, and obesity and visceral adiposity are associated with numerous metabolic and inflammatory sequelae. However, HIV- and antiretroviral therapy (ART)-specific factors may contribute to fat gain and fat quality in treated HIV infection, particularly to the development of visceral adiposity, and sex differences may exist.

Summary

Obesity and visceral adiposity commonly occur in HIV-infected persons and have significant implications for morbidity and mortality. Future research should aim to better elucidate the HIV- and ART-specific contributors to obesity and visceral adiposity in treated HIV infection, with the goal of developing targeted therapies for the prevention and treatment of obesity and visceral adiposity in the modern ART era.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Hamdy OUG, Oral EA Obesity practice essentials. Medscape. 2016.

  2. Study of Fat Redistribution and Metabolic Change in HIV Infection. Fat distribution in women with HIV infection. J Acquir Immune Defic Syndr. 2006;42(5):562–71. https://doi.org/10.1097/01.qai.0000229996.75116.da.

    Article  Google Scholar 

  3. Brown TT, Xu X, John M, Singh J, Kingsley LA, Palella FJ, et al. Fat distribution and longitudinal anthropometric changes in HIV-infected men with and without clinical evidence of lipodystrophy and HIV-uninfected controls: a substudy of the Multicenter AIDS Cohort Study. AIDS Res Ther. 2009;6:8. https://doi.org/10.1186/1742-6405-6-8.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Joy T, Keogh HM, Hadigan C, Dolan SE, Fitch K, Liebau J, et al. Relation of body composition to body mass index in HIV-infected patients with metabolic abnormalities. J Acquir Immune Defic Syndr. 2008;47(2):174–84. https://doi.org/10.1097/QAI.0b013e31815b0792.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Buchacz K, Baker RK, Palella FJ Jr, Shaw L, Patel P, Lichtenstein KA, et al. Disparities in prevalence of key chronic diseases by gender and race/ethnicity among antiretroviral-treated HIV-infected adults in the US. Antivir Ther. 2013;18(1):65–75. https://doi.org/10.3851/IMP2450.

    Article  PubMed  Google Scholar 

  6. Levy ME, Greenberg AE, Hart R, Powers Happ L, Hadigan C, Castel A, et al. High burden of metabolic comorbidities in a citywide cohort of HIV outpatients: evolving health care needs of people aging with HIV in Washington, DC. HIV Med. 2017; https://doi.org/10.1111/hiv.12516.

  7. Hernandez D, Kalichman S, Cherry C, Kalichman M, Washington C, Grebler T. Dietary intake and overweight and obesity among persons living with HIV in Atlanta Georgia. AIDS Care. 2017;29(6):767–71. https://doi.org/10.1080/09540121.2016.1238441.

    Article  PubMed  Google Scholar 

  8. Erlandson KM, Taejaroenkul S, Smeaton L, Gupta A, Singini IL, Lama JR, et al. A randomized comparison of anthropomorphic changes with preferred and alternative Efavirenz-based antiretroviral regimens in diverse multinational settings. Open Forum Infect Dis. 2015;2(3):ofv095. https://doi.org/10.1093/ofid/ofv095.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Achhra AC, Mocroft A, Reiss P, Sabin C, Ryom L, de Wit S, et al. Short-term weight gain after antiretroviral therapy initiation and subsequent risk of cardiovascular disease and diabetes: the D:A:D study. HIV Med. 2016;17(4):255–68. https://doi.org/10.1111/hiv.12294.

    Article  CAS  PubMed  Google Scholar 

  10. Lakey W, Yang LY, Yancy W, Chow SC, Hicks C. Short communication: from wasting to obesity: initial antiretroviral therapy and weight gain in HIV-infected persons. AIDS Res Hum Retrovir. 2013;29(3):435–40. https://doi.org/10.1089/AID.2012.0234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. • McComsey GA, Moser C, Currier J, Ribaudo HJ, Paczuski P, Dube MP, et al. Body composition changes after initiation of Raltegravir or protease inhibitors: ACTG A5260s. Clin Infect Dis. 2016;62(7):853–62. https://doi.org/10.1093/cid/ciw017. A well-designed, head-to-head comparison of the metabolic effects of modern protease inhibitor- vs integrase strand transfer inhibitor-based ART.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Mave V, Erlandson KM, Gupte N, Balagopal A, Asmuth DM, Campbell TB, et al. Inflammation and change in body weight with antiretroviral therapy initiation in a multinational cohort of HIV-infected adults. J Infect Dis. 2016;214(1):65–72. https://doi.org/10.1093/infdis/jiw096.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Yuh B, Tate J, Butt AA, Crothers K, Freiberg M, Leaf D, et al. Weight change after antiretroviral therapy and mortality. Clin Infect Dis. 2015;60(12):1852–9. https://doi.org/10.1093/cid/civ192.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kim DJ, Westfall AO, Chamot E, Willig AL, Mugavero MJ, Ritchie C, et al. Multimorbidity patterns in HIV-infected patients: the role of obesity in chronic disease clustering. J Acquir Immune Defic Syndr. 2012;61(5):600–5. https://doi.org/10.1097/QAI.0b013e31827303d5.

    Article  PubMed  PubMed Central  Google Scholar 

  15. • Grant PM, Kitch D, McComsey GA, Collier AC, Bartali B, Koletar SL, et al. Long-term body composition changes in antiretroviral-treated HIV-infected individuals. AIDS. 2016;30(18):2805–13. https://doi.org/10.1097/QAD.0000000000001248. The longest published follow-up of body composiiton changes following ART initiation in HIV-infected persons, with comparison to an HIV-uninfected control group.

    Article  CAS  PubMed  Google Scholar 

  16. Bhagwat P, Ofotokun I, McComsey GA, Brown TT, Moser C, Sugar CA, et al. Changes in abdominal fat following antiretroviral therapy initiation in HIV-infected individuals correlate with waist circumference and self-reported changes. Antivir Ther. 2017; https://doi.org/10.3851/IMP3148.

  17. Bhagwat POI, McComsey GA, Brown TT, Moser C, Sugar CA, Currier JS. Raltegravir is associated with greater abdominal fat increases after antiretroviral therapy initiation compared to protease inhibitors. Abstracts from the 18th International Workshop of Co-morbidities and Adverse Drug Reactions in HIV. 2016.

  18. Shah RV, Murthy VL, Abbasi SA, Blankstein R, Kwong RY, Goldfine AB, et al. Visceral adiposity and the risk of metabolic syndrome across body mass index: the MESA Study. JACC Cardiovasc Imaging. 2014;7(12):1221–35. https://doi.org/10.1016/j.jcmg.2014.07.017.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Scherzer R, Heymsfield SB, Lee D, Powderly WG, Tien PC, Bacchetti P, et al. Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection. AIDS. 2011;25(11):1405–14. https://doi.org/10.1097/QAD.0b013e32834884e6.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Lynch LA, O'Connell JM, Kwasnik AK, Cawood TJ, O'Farrelly C, O'Shea DB. Are natural killer cells protecting the metabolically healthy obese patient? Obesity (Silver Spring). 2009;17(3):601–5. https://doi.org/10.1038/oby.2008.565.

    Article  CAS  Google Scholar 

  21. Brochu M, Tchernof A, Dionne IJ, Sites CK, Eltabbakh GH, Sims EA, et al. What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women? J Clin Endocrinol Metab. 2001;86(3):1020–5. https://doi.org/10.1210/jcem.86.3.7365.

    CAS  PubMed  Google Scholar 

  22. Phillips CM, Perry IJ. Does inflammation determine metabolic health status in obese and nonobese adults? J Clin Endocrinol Metab. 2013;98(10):E1610–9. https://doi.org/10.1210/jc.2013-2038.

    Article  CAS  PubMed  Google Scholar 

  23. Pujia A, Gazzaruso C, Ferro Y, Mazza E, Maurotti S, Russo C et al. Individuals with metabolically healthy overweight/obesity have higher fat utilization than metabolically unhealthy individuals. Nutrients. 2016;8(1). doi:https://doi.org/10.3390/nu8010002.

  24. Yoon JW, Jung CH, Kim MK, Park HE, Park KS, Jang HC, et al. Influence of the definition of “metabolically healthy obesity” on the progression of coronary artery calcification. PLoS One. 2017;12(6):e0178741. https://doi.org/10.1371/journal.pone.0178741.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Zheng R, Liu C, Wang C, Zhou B, Liu Y, Pan F, et al. Natural course of metabolically healthy overweight/obese subjects and the impact of weight change. Nutrients. 2016;8(7):430. https://doi.org/10.3390/nu8070430.

    Article  PubMed Central  Google Scholar 

  26. Lake JE LX, Palella FJ, Erlandson K, Wiley D, Kingsley L, Jacobson LP, Brown TT. Metabolic health across the body mass index spectrum in HIV-infected and HIV-uninfected men. Abstracts from the 17th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV. 2015.

  27. Bourlier V, Sengenes C, Zakaroff-Girard A, Decaunes P, Wdziekonski B, Galitzky J, et al. TGFbeta family members are key mediators in the induction of myofibroblast phenotype of human adipose tissue progenitor cells by macrophages. PLoS One. 2012;7(2):e31274. https://doi.org/10.1371/journal.pone.0031274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Haase J, Weyer U, Immig K, Kloting N, Bluher M, Eilers J, et al. Local proliferation of macrophages in adipose tissue during obesity-induced inflammation. Diabetologia. 2014;57(3):562–71. https://doi.org/10.1007/s00125-013-3139-y.

    Article  CAS  PubMed  Google Scholar 

  29. Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011;17(2):179–88. https://doi.org/10.1038/nm.2279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Brestoff JR, Artis D. Immune regulation of metabolic homeostasis in health and disease. Cell. 2015;161(1):146–60. https://doi.org/10.1016/j.cell.2015.02.022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hong KM, Burdick MD, Phillips RJ, Heber D, Strieter RM. Characterization of human fibrocytes as circulating adipocyte progenitors and the formation of human adipose tissue in SCID mice. FASEB J. 2005;19(14):2029–31. https://doi.org/10.1096/fj.05-4295fje.

    CAS  PubMed  Google Scholar 

  32. Divoux A, Tordjman J, Lacasa D, Veyrie N, Hugol D, Aissat A, et al. Fibrosis in human adipose tissue: composition, distribution, and link with lipid metabolism and fat mass loss. Diabetes. 2010;59(11):2817–25. https://doi.org/10.2337/db10-0585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gaggini M, Saponaro C, Gastaldelli A. Not all fats are created equal: adipose vs. ectopic fat, implication in cardiometabolic diseases. Horm Mol Biol Clin Investig. 2015;22(1):7–18. https://doi.org/10.1515/hmbci-2015-0006.

    CAS  PubMed  Google Scholar 

  34. Giralt M, Domingo P, Villarroya F. Adipose tissue biology and HIV-infection. Best Pract Res Clin Endocrinol Metab. 2011;25(3):487–99. https://doi.org/10.1016/j.beem.2010.12.001.

    Article  CAS  PubMed  Google Scholar 

  35. Lim S, Meigs JB. Links between ectopic fat and vascular disease in humans. Arterioscler Thromb Vasc Biol. 2014;34(9):1820–6. https://doi.org/10.1161/ATVBAHA.114.303035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Orlando G, Guaraldi G, Zona S, Carli F, Bagni P, Menozzi M, et al. Ectopic fat is linked to prior cardiovascular events in men with HIV. J Acquir Immune Defic Syndr. 2012;59(5):494–7. https://doi.org/10.1097/QAI.0b013e31824c8397.

    Article  PubMed  Google Scholar 

  37. Koethe JR, Hulgan T, Niswender K. Adipose tissue and immune function: a review of evidence relevant to HIV infection. J Infect Dis. 2013;208(8):1194–201. https://doi.org/10.1093/infdis/jit324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. de Souza Dantas Oliveira SH, de Souza Aarao TL, da Silva Barbosa L, Souza Lisboa PG, Tavares Dutra CD, Margalho Sousa L, et al. Immunohistochemical analysis of the expression of TNF-alpha, TGF-beta, and caspase-3 in subcutaneous tissue of patients with HIV lipodystrophy syndrome. Microb Pathog. 2014;67-68:41–7. https://doi.org/10.1016/j.micpath.2014.02.004.

    Article  PubMed  Google Scholar 

  39. Utay NS KD, Fichtenbaum C, Lederman MM, Estes JD, Magyar C, Klingman KL, Currier JS, Lake JE. Telmisartan does not improve lymph node or fat fibrosis in treated HIV infection. Abstracts from the 2017 Conference on Retroviruses and Opportunistic Infections. 2017.

  40. •• Damouche A, Lazure T, Avettand-Fenoel V, Huot N, Dejucq-Rainsford N, Satie AP, et al. Adipose tissue is a neglected viral reservoir and an inflammatory site during chronic HIV and SIV infection. PLoS Pathog. 2015;11(9):e1005153. https://doi.org/10.1371/journal.ppat.1005153. A landmark paper identifying adipose tisue as a potential reservoir for HIV infection.

    Article  PubMed  PubMed Central  Google Scholar 

  41. • Agarwal N, Balasubramanyam A. Viral mechanisms of adipose dysfunction: lessons from HIV-1 Vpr. Adipocyte. 2015;4(1):55–9. https://doi.org/10.4161/adip.29852. Outlines an animal model important to our understanding of HIV-specific effects on adipose tissue.

    Article  CAS  PubMed  Google Scholar 

  42. •• Couturier J, Suliburk JW, Brown JM, Luke DJ, Agarwal N, Yu X, et al. Human adipose tissue as a reservoir for memory CD4+ T cells and HIV. AIDS. 2015;29(6):667–74. https://doi.org/10.1097/QAD.0000000000000599. The second landmark paper identifying adipose tisue as a potential reservoir for HIV infection.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Balagopal A, Philp FH, Astemborski J, Block TM, Mehta A, Long R, et al. Human immunodeficiency virus-related microbial translocation and progression of hepatitis C. Gastroenterology. 2008;135(1):226–33. https://doi.org/10.1053/j.gastro.2008.03.022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Arslan N. Obesity, fatty liver disease and intestinal microbiota. World J Gastroenterol. 2014;20(44):16452–63. https://doi.org/10.3748/wjg.v20.i44.16452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Masia M, Padilla S, Alvarez D, Lopez JC, Santos I, Soriano V, et al. Risk, predictors, and mortality associated with non-AIDS events in newly diagnosed HIV-infected patients: role of antiretroviral therapy. AIDS. 2013;27(2):181–9. https://doi.org/10.1097/QAD.0b013e32835a1156.

    Article  CAS  PubMed  Google Scholar 

  46. Weber R, Ruppik M, Rickenbach M, Spoerri A, Furrer H, Battegay M, et al. Decreasing mortality and changing patterns of causes of death in the Swiss HIV Cohort Study. HIV Med. 2013;14(4):195–207. https://doi.org/10.1111/j.1468-1293.2012.01051.x.

    Article  CAS  PubMed  Google Scholar 

  47. Conley LJ, Bush TJ, Rupert AW, Sereti I, Patel P, Brooks JT, et al. Obesity is associated with greater inflammation and monocyte activation among HIV-infected adults receiving antiretroviral therapy. AIDS. 2015;29(16):2201–7. https://doi.org/10.1097/QAD.0000000000000817.

    Article  CAS  PubMed  Google Scholar 

  48. Bonamichi B, Lee J. Unusual suspects in the development of obesity-induced inflammation and insulin resistance: NK cells, iNKT cells, and ILCs. Diabetes Metab J. 2017;

  49. Stambullian M, Feliu MS, Cassetti LI, Slobodianik NH. Nutritional status and lipid profile in HIV-infected adults. Endocr Metab Immune Disord Drug Targets. 2015;15(4):302–7.

    Article  CAS  PubMed  Google Scholar 

  50. Hulgan T, Boger MS, Liao DH, McComsey GA, Wanke CA, Mangili A, et al. Urinary eicosanoid metabolites in HIV-infected women with central obesity switching to raltegravir: an analysis from the women, integrase, and fat accumulation trial. Mediat Inflamm. 2014;2014:803095. https://doi.org/10.1155/2014/803095.

    Article  Google Scholar 

  51. Vidal F, Domingo P, Villarroya F, Giralt M, Lopez-Dupla M, Gutierrez M, et al. Adipogenic/lipid, inflammatory, and mitochondrial parameters in subcutaneous adipose tissue of untreated HIV-1-infected long-term nonprogressors: significant alterations despite low viral burden. J Acquir Immune Defic Syndr. 2012;61(2):131–7. https://doi.org/10.1097/QAI.0b013e31825c3a68.

    Article  CAS  PubMed  Google Scholar 

  52. Diaz-Delfin J, Domingo P, Wabitsch M, Giralt M, Villarroya F. HIV-1 Tat protein impairs adipogenesis and induces the expression and secretion of proinflammatory cytokines in human SGBS adipocytes. Antivir Ther. 2012;17(3):529–40. https://doi.org/10.3851/IMP2021.

    Article  CAS  PubMed  Google Scholar 

  53. Guaraldi G, Luzi K, Bellistri GM, Zona S, Domingues da Silva AR, Bai F, et al. CD8 T-cell activation is associated with lipodystrophy and visceral fat accumulation in antiretroviral therapy-treated virologically suppressed HIV-infected patients. J Acquir Immune Defic Syndr. 2013;64(4):360–6. https://doi.org/10.1097/QAI.0000000000000001.

    Article  CAS  PubMed  Google Scholar 

  54. Srinivasa S, Fitch KV, Wong K, Torriani M, Mayhew C, Stanley T, et al. RAAS activation is associated with visceral adiposity and insulin resistance among HIV-infected patients. J Clin Endocrinol Metab. 2015;100(8):2873–82. https://doi.org/10.1210/jc.2015-1461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Boccara F, Auclair M, Cohen A, Lefevre C, Prot M, Bastard JP, et al. HIV protease inhibitors activate the adipocyte renin angiotensin system. Antivir Ther. 2010;15(3):363–75. https://doi.org/10.3851/IMP1533.

    Article  CAS  PubMed  Google Scholar 

  56. • Srinivasa S, Fitch KV, Wong K, Torriani M, Mayhew C, Stanley T et al. RAAS activation is associated with visceral adiposity and insulin resistance among HIV-infected patients. J Clin Endocrinol Metab. 2015:jc20151461. doi:https://doi.org/10.1210/jc.2015-1461. This study represents an important step in our understanding of the relationship between renin-angiotensin system activation, visceral adiposity and its sequelae in HIV infection.

  57. Gerard P. Gut microbiota and obesity. Cell Mol Life Sci. 2016;73(1):147–62. https://doi.org/10.1007/s00018-015-2061-5.

    Article  CAS  PubMed  Google Scholar 

  58. Rietschel P, Hadigan C, Corcoran C, Stanley T, Neubauer G, Gertner J, et al. Assessment of growth hormone dynamics in human immunodeficiency virus-related lipodystrophy. J Clin Endocrinol Metab. 2001;86(2):504–10. https://doi.org/10.1210/jcem.86.2.7175.

    CAS  PubMed  Google Scholar 

  59. Tchkonia T, Morbeck DE, Von Zglinicki T, Van Deursen J, Lustgarten J, Scrable H, et al. Fat tissue, aging, and cellular senescence. Aging Cell. 2010;9(5):667–84. https://doi.org/10.1111/j.1474-9726.2010.00608.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Freitas P, Carvalho D, Santos AC, Madureira AJ, Martinez E, Pereira J, et al. Adipokines, hormones related to body composition, and insulin resistance in HIV fat redistribution syndrome. BMC Infect Dis. 2014;14:347. https://doi.org/10.1186/1471-2334-14-347.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Palella FJ Jr, McKibben R, Post WS, Li X, Budoff M, Kingsley L, et al. Anatomic fat depots and coronary plaque among human immunodeficiency virus-infected and uninfected men in the Multicenter AIDS Cohort Study. Open Forum Infect Dis. 2016;3(2):ofw098. https://doi.org/10.1093/ofid/ofw098.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Samaras K. The burden of diabetes and hyperlipidemia in treated HIV infection and approaches for cardiometabolic care. Curr HIV/AIDS Rep. 2012;9(3):206–17. https://doi.org/10.1007/s11904-012-0124-x.

    Article  PubMed  Google Scholar 

  63. Durand M, Sheehy O, Baril JG, Lelorier J, Tremblay CL. Association between HIV infection, antiretroviral therapy, and risk of acute myocardial infarction: a cohort and nested case-control study using Quebec’s public health insurance database. J Acquir Immune Defic Syndr. 2011;57(3):245–53. https://doi.org/10.1097/QAI.0b013e31821d33a5.

    Article  PubMed  Google Scholar 

  64. Islam FM, Wu J, Jansson J, Wilson DP. Relative risk of cardiovascular disease among people living with HIV: a systematic review and meta-analysis. HIV Med. 2012;13(8):453–68. https://doi.org/10.1111/j.1468-1293.2012.00996.x.

    CAS  PubMed  Google Scholar 

  65. Koethe JR, Grome H, Jenkins CA, Kalams SA, Sterling TR. The metabolic and cardiovascular consequences of obesity in persons with HIV on long-term antiretroviral therapy. AIDS. 2016;30(1):83–91. https://doi.org/10.1097/QAD.0000000000000893.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Seang SKT, Currier JS, Lake JE. Endothelial progenitor cell production is suppressed and associated with systemic inflammation and monocyte activation in older HIV-infected men. Abstracts from IDWeek 2016. 2016.

  67. Guaraldi G, Squillace N, Stentarelli C, Orlando G, D'Amico R, Ligabue G, et al. Nonalcoholic fatty liver disease in HIV-infected patients referred to a metabolic clinic: prevalence, characteristics, and predictors. Clin Infect Dis. 2008;47(2):250–7. https://doi.org/10.1086/589294.

    Article  PubMed  Google Scholar 

  68. Crum-Cianflone N, Dilay A, Collins G, Asher D, Campin R, Medina S, et al. Nonalcoholic fatty liver disease among HIV-infected persons. J Acquir Immune Defic Syndr. 2009;50(5):464–73. https://doi.org/10.1097/QAI.0b013e318198a88a.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Hadigan C, Liebau J, Andersen R, Holalkere NS, Sahani DV. Magnetic resonance spectroscopy of hepatic lipid content and associated risk factors in HIV infection. J Acquir Immune Defic Syndr. 2007;46(3):312–7. https://doi.org/10.1097/QAI.0b013e3181568cc2.

    Article  PubMed  Google Scholar 

  70. Morse CG, McLaughlin M, Matthews L, Proschan M, Thomas F, Gharib AM, et al. Nonalcoholic steatohepatitis and hepatic fibrosis in HIV-1-monoinfected adults with elevated aminotransferase levels on antiretroviral therapy. Clin Infect Dis. 2015;60(10):1569–78. https://doi.org/10.1093/cid/civ101.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Schuppan D, Schattenberg JM. Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches. J Gastroenterol Hepatol. 2013;28(Suppl 1):68–76. https://doi.org/10.1111/jgh.12212.

    Article  CAS  PubMed  Google Scholar 

  72. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010;363(14):1341–50. https://doi.org/10.1056/NEJMra0912063.

    Article  CAS  PubMed  Google Scholar 

  73. Lonardo A, Ballestri S, Guaraldi G, Nascimbeni F, Romagnoli D, Zona S, et al. Fatty liver is associated with an increased risk of diabetes and cardiovascular disease - evidence from three different disease models: NAFLD, HCV and HIV. World J Gastroenterol. 2016;22(44):9674–93. https://doi.org/10.3748/wjg.v22.i44.9674.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Oni ET, Agatston AS, Blaha MJ, Fialkow J, Cury R, Sposito A, et al. A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care? Atherosclerosis. 2013;230(2):258–67. https://doi.org/10.1016/j.atherosclerosis.2013.07.052.

    Article  CAS  PubMed  Google Scholar 

  75. Fabbrini E, Magkos F, Mohammed BS, Pietka T, Abumrad NA, Patterson BW, et al. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc Natl Acad Sci U S A. 2009;106(36):15430–5. https://doi.org/10.1073/pnas.0904944106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Korenblat KM, Fabbrini E, Mohammed BS, Klein S. Liver, muscle, and adipose tissue insulin action is directly related to intrahepatic triglyceride content in obese subjects. Gastroenterology. 2008;134(5):1369–75. https://doi.org/10.1053/j.gastro.2008.01.075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Vallet-Pichard A, Mallet V, Pol S. Nonalcoholic fatty liver disease and HIV infection. Semin Liver Dis. 2012;32(2):158–66. https://doi.org/10.1055/s-0032-1316471.

    Article  CAS  PubMed  Google Scholar 

  78. Vodkin I, Valasek MA, Bettencourt R, Cachay E, Loomba R. Clinical, biochemical and histological differences between HIV-associated NAFLD and primary NAFLD: a case-control study. Aliment Pharmacol Ther. 2015;41(4):368–78. https://doi.org/10.1111/apt.13052.

    Article  CAS  PubMed  Google Scholar 

  79. Ghazarian M, Revelo XS, Nohr MK, Luck H, Zeng K, Lei H et al. Type I interferon responses drive intrahepatic T cells to promote metabolic syndrome. Sci Immunol. 2017;2(10). doi:https://doi.org/10.1126/sciimmunol.aai7616.

  80. Ray I, Mahata SK, De RK. Obesity: an immunometabolic perspective. Front Endocrinol (Lausanne). 2016;7:157. https://doi.org/10.3389/fendo.2016.00157.

    Google Scholar 

  81. Zanni MV, Schouten J, Grinspoon SK, Reiss P. Risk of coronary heart disease in patients with HIV infection. Nat Rev Cardiol. 2014;11(12):728–41. https://doi.org/10.1038/nrcardio.2014.167.

    Article  CAS  PubMed  Google Scholar 

  82. Matthews L, Kleiner DE, Chairez C, McManus M, Nettles MJ, Zemanick K, et al. Pioglitazone for hepatic steatosis in HIV/hepatitis C virus coinfection. AIDS Res Hum Retrovir. 2015;31(10):961–6. https://doi.org/10.1089/AID.2015.0093.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, et al. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014;312(4):380–9. https://doi.org/10.1001/jama.2014.8334.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Tafesh ZH, Verna EC. Managing nonalcoholic fatty liver disease in patients living with HIV. Curr Opin Infect Dis. 2017;30(1):12–20. https://doi.org/10.1097/QCO.0000000000000344.

    PubMed  Google Scholar 

  85. Lemieux S, Prud'homme D, Bouchard C, Tremblay A, Despres JP. A single threshold value of waist girth identifies normal-weight and overweight subjects with excess visceral adipose tissue. Am J Clin Nutr. 1996;64(5):685–93.

    CAS  PubMed  Google Scholar 

  86. Sattler FR, He J, Letendre S, Wilson C, Sanders C, Heaton R, et al. Abdominal obesity contributes to neurocognitive impairment in HIV-infected patients with increased inflammation and immune activation. J Acquir Immune Defic Syndr. 2015;68(3):281–8. https://doi.org/10.1097/QAI.0000000000000458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Okafor CN, Kelso NE, Bryant V, Burrell LE 2nd, Miguez MJ, Gongvatana A, et al. Body mass index, inflammatory biomarkers and neurocognitive impairment in HIV-infected persons. Psychol Health Med. 2017;22(3):289–302. https://doi.org/10.1080/13548506.2016.1199887.

    Article  PubMed  Google Scholar 

  88. Gustafson DR, Mielke MM, Keating SA, Holman S, Minkoff H, Crystal HA. Leptin, adiponectin and cognition in middle-aged HIV-infected and uninfected women. The Brooklyn women’s interagency HIV study. J Gerontol Geriatr Res. 2015;4(5) https://doi.org/10.4172/2167-7182.1000240.

  89. • Lake JE, Popov M, Post WS, Palella FJ Jr, Sacktor N, Miller EN, et al. Visceral fat is associated with brain structure independent of human immunodeficiency virus infection status. J Neuro-Oncol. 2017;23(3):385–93. https://doi.org/10.1007/s13365-016-0507-7. This analysis of Multicenter AIDS Cohort participants documents increased VAT quantity as the clinical factor most strongly associated with brain atrophy, irrespective of HIV infection status.

    CAS  Google Scholar 

  90. Erlandson KM, Wu K, Koletar SL, Kalayjian RC, Ellis RJ, Taiwo B, et al. Association between frailty and components of the frailty phenotype with modifiable risk factors and antiretroviral therapy. J Infect Dis. 2017;215(6):933–7. https://doi.org/10.1093/infdis/jix063.

    Article  PubMed  Google Scholar 

  91. Shah K, Hilton TN, Myers L, Pinto JF, Luque AE, Hall WJ. A new frailty syndrome: central obesity and frailty in older adults with the human immunodeficiency virus. J Am Geriatr Soc. 2012;60(3):545–9. https://doi.org/10.1111/j.1532-5415.2011.03819.x.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Young P, Shah J, Zhang C, Ferris DC, Colon I, Bucovsky M, et al. Frailty in postmenopausal African American and Hispanic HIV-infected women. J Frailty Aging. 2016;5(4):242–6. 10.14283/jfa.2016.104.

    CAS  PubMed  Google Scholar 

  93. Bauer LO, Wu Z, Wolfson LI. An obese body mass increases the adverse effects of HIV/AIDS on balance and gait. Phys Ther. 2011;91(7):1063–71. https://doi.org/10.2522/ptj.20100292.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Sharma A, Hoover DR, Shi Q, Holman S, Plankey MW, Wheeler AL, et al. Falls among middle-aged women in the Women’s Interagency HIV Study. Antivir Ther. 2016;21(8):697–706. https://doi.org/10.3851/IMP3070.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Shah KN, Majeed Z, Yang H, Guido JJ, Hilton TN, Polesskaya O, et al. Functional limitations and adipokines in Hiv-infected older adults. J Frailty Aging. 2015;4(1):41–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Margolick JB, Bream JH, Martinez-Maza O, Lopez J, Li X, Phair JP, et al. Frailty and circulating markers of inflammation in HIV+ and HIV- men in the Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr. 2017;74(4):407–17. https://doi.org/10.1097/QAI.0000000000001261.

    Article  PubMed  Google Scholar 

  97. Erlandson KM, Ng DK, Jacobson LP, Margolick JB, Dobs AS, Palella FJ Jr, et al. Inflammation, immune activation, Immunosenescence, and hormonal biomarkers in the frailty-related phenotype of men with or at risk for HIV infection. J Infect Dis. 2017;215(2):228–37. https://doi.org/10.1093/infdis/jiw523.

    PubMed  Google Scholar 

  98. Schrack JA, Althoff KN, Jacobson LP, Erlandson KM, Jamieson BD, Koletar SL, et al. Accelerated longitudinal gait speed decline in HIV-infected older men. J Acquir Immune Defic Syndr. 2015;70(4):370–6. https://doi.org/10.1097/QAI.0000000000000731.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Schrack JA, Jacobson LP, Althoff KN, Erlandson KM, Jamieson BD, Koletar SL, et al. Effect of HIV-infection and cumulative viral load on age-related decline in grip strength. AIDS. 2016;30(17):2645–52. https://doi.org/10.1097/QAD.0000000000001245.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Erlandson KM, Allshouse AA, Jankowski CM, MaWhinney S, Kohrt WM, Campbell TB. Functional impairment is associated with low bone and muscle mass among persons aging with HIV infection. J Acquir Immune Defic Syndr. 2013;63(2):209–15. https://doi.org/10.1097/QAI.0b013e318289bb7e.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Pinto Neto LF, Sales MC, Scaramussa ES, da Paz CJ, Morelato RL. Human immunodeficiency virus infection and its association with sarcopenia. The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases. 2016;20(1):99–102. https://doi.org/10.1016/j.bjid.2015.10.003.

    Article  Google Scholar 

  102. •• Lake JE, Stanley TL, Apovian CM, Bhasin S, Brown TT, Capeau J, et al. Practical review of recognition and management of obesity and lipohypertrophy in human immunodeficiency virus infection. Clin Infect Dis. 2017;64(10):1422–9. https://doi.org/10.1093/cid/cix178. This article provides a concise, up-to-date consensus statement for the clinician on the diagnosis, pathophysiology, clinical assessment and treatment of obesity and lipohypertrophy in treated HIV infection.

    Article  PubMed  Google Scholar 

  103. Engelson ES, Agin D, Kenya S, Werber-Zion G, Luty B, Albu JB, et al. Body composition and metabolic effects of a diet and exercise weight loss regimen on obese, HIV-infected women. Metabolism. 2006;55(10):1327–36. https://doi.org/10.1016/j.metabol.2006.05.018.

    Article  CAS  PubMed  Google Scholar 

  104. Terry L, Sprinz E, Stein R, Medeiros NB, Oliveira J, Ribeiro JP. Exercise training in HIV-1-infected individuals with dyslipidemia and lipodystrophy. Med Sci Sports Exerc. 2006;38(3):411–7. https://doi.org/10.1249/01.mss.0000191347.73848.80.

    Article  CAS  PubMed  Google Scholar 

  105. Mutimura E, Crowther NJ, Cade TW, Yarasheski KE, Stewart A. Exercise training reduces central adiposity and improves metabolic indices in HAART-treated HIV-positive subjects in Rwanda: a randomized controlled trial. AIDS Res Hum Retrovir. 2008;24(1):15–23. https://doi.org/10.1089/aid.2007.0023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Becofsky K, Wing EJ, McCaffery J, Bodreau M, Wing RR. A randomized, controlled trial of a behavioral weight loss program for HIV-infected patients. Clin Infect Dis. 2017; https://doi.org/10.1093/cid/cix238.

  107. Reeds DN, Pietka TA, Yarasheski KE, Cade WT, Patterson BW, Okunade A, et al. HIV infection does not prevent the metabolic benefits of diet-induced weight loss in women with obesity. Obesity (Silver Spring). 2017;25(4):682–8. https://doi.org/10.1002/oby.21793.

    Article  CAS  PubMed Central  Google Scholar 

  108. Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014;129(25 Suppl 2):S102–38. https://doi.org/10.1161/01.cir.0000437739.71477.ee.

    Article  PubMed  Google Scholar 

  109. Munro S, Dinatale E, Hartley S, St Jacques M, Oursler KA. Barriers and health beliefs related to weight management among veterans with human immunodeficiency virus. Mil Med. 2017;182(1):e1596–e602. https://doi.org/10.7205/MILMED-D-16-00086.

    Article  PubMed  Google Scholar 

  110. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, et al. Association of Pharmacological Treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA. 2016;315(22):2424–34. https://doi.org/10.1001/jama.2016.76022528211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by National Institutes of Health grants K23 AI110532 to JEL.

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  1. University of Texas Health Science Center at Houston, 6431 Fannin St., MSB 2.112, Houston, TX, 77030, USA

    Jordan E. Lake

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Jordan E. Lake has received research funding through her institution from Gilead Sciences and GSK, and has served as a consultant to Merck, Sharp and Dohme, Gilead Sciences and GSK.

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All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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This article is part of the Topical Collection on Complications of Antiretroviral Therapy

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Lake, J.E. The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection. Curr HIV/AIDS Rep 14, 211–219 (2017). https://doi.org/10.1007/s11904-017-0368-6

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