Top

Published in:

01-09-2011

Management of Fat Accumulation in Patients with HIV Infection

Author: Julian Falutz

Published in: Current HIV/AIDS Reports | Issue 3/2011

Abstract

The use of antiretroviral therapies has improved survival in people living with HIV to nearly normal rates. However, ongoing low-level HIV replication and incomplete immune recovery are associated with a chronic inflammatory stimulus. This increases several non-typically AIDS-related complications, including fat mass changes and metabolic conditions. Abdominal adiposity occurs as a result of complex interactions involving HIV itself, antiretroviral drug–associated factors, and several intermediary metabolic alterations and abnormal hormone levels. Abdominal adiposity in turn can further the metabolic derangements, and increase the risk of diabetes and cardiovascular disease. Abnormal growth hormone secretion plays a role in development of the fat depot changes. Effective long-term interventions to decrease central adiposity are limited but studies using growth hormone and especially growth hormone–releasing factor have shown encouraging results. Other emerging therapeutic options have been variably successful in the short term and the continuing clinical and therapeutic challenges will require ongoing investigation.

• Hogg R, Lima V, Sterne J, et al. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet. 2008;372:293–9. This is an important large collaborative cohort analysis using careful modelling tools to show that overall survival for treated HIV patients has improved significantly since the introduction of HAART in 1996, but that it remains at about 66% that of the general population. Subgroup differences, especially age, are clearly evident.CrossRef

Kelley CF, Kitchen CM, Hunt PW, et al. Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis. 2009;48:787–94.PubMedCrossRef

Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med. 2011;62:141–55.PubMedCrossRef

Achhra AC, Amin J, Law MG, et al. Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients. AIDS. 2010;24:1877–86.PubMedCrossRef

Baker JV, Peng G, Rapkin J, et al. CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection. AIDS. 2008;22:841–8.PubMedCrossRef

Lichtenstein KA, Armon C, Buchacz K, et al. Low CD4+ T cell count is a risk factor for cardiovascular disease events in the HIV outpatient study. Clin Infect Dis. 2010;51:435–47.PubMedCrossRef

Heaton RK, Clifford DB, Franklin Jr DR, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010;75:2087–96.PubMedCrossRef

McComsey GA, Tebas P, Shane E, et al. Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis. 2010;51:937–46.PubMedCrossRef

Falutz J. HIV infection, body composition changes and related metabolic complications: contributing factors and evolving management strategies. Curr Opin Clin Nutr Metab Care. 2011. doi:10.1097/MCO.0b013e3283457a8f.

10.

Scherzer R, Heymsfield S, Lee D, et al. Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection. Abstract No.76. Presented at the 18th Conference on Retroviruses and Opportunistic Infections. Boston, MA. February, 2011.

11.

Kotler DP, Rosenbaum K, Wang J, et al. Studies of body composition and fat distribution in HIV-infected and control subjects. J Acquir Immune Defic Syndr Hum Retrovirol. 1999;20:228–37.PubMedCrossRef

12.

Decrion AZ, Dichamp I, Varin A, et al. HIV and inflammation. Curr HIV Res. 2005;3:243–59.PubMedCrossRef

13.

• Hsue PY, Hunt PW, Schnell A, et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS. 2009;23:1059–67. This is an important study of ongoing inflammation in patients with controlled HIV replication and its association with clinical sequelae. In this analysis, accelerated atherosclerosis was studied using carotid intima-medial thickening (cIMT) as the surrogate. Both CRP and cIMT were increased in patients with HIV controlled by HAART and in those few patients able to maintain high-level control of HIV without HAART ("elite controllers").PubMedCrossRef

14.

Schaffler A, Muller-Ladner U, Scholmerich J, et al. Role of adipose tissue as an inflammatory organ in human diseases. Endocr Rev. 2006;27:449–67.PubMedCrossRef

15.

Giles JT, Allison M, Blumenthal RS, et al. Abdominal adiposity in rheumatoid arthritis: association with cardiometabolic risk factors and disease characteristics. Arthritis Rheum. 2010;62:3173–82.PubMedCrossRef

16.

Carr A, Samaras K, Burton S, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998;12:F51–8.PubMedCrossRef

17.

Mallon PW, Wand H, Law M, et al. Buffalo hump seen in HIV-associated lipodystrophy is associated with hyperinsulinemia but not dyslipidemia. J Acquir Immune Defic Syndr. 2005;38:156–62.PubMedCrossRef

18.

He Q, Engelson ES, Ionescu G, et al. Insulin resistance, hepatic lipid and adipose tissue distribution in HIV-infected men. Antivir Ther. 2008;13:423–8.PubMed

19.

Lo J, Abbara S, Rocha-Filho JA, et al. Increased epicardial adipose tissue volume in HIV-infected men and relationships to body composition and metabolic parameters. AIDS. 2010;24:2127–30.PubMedCrossRef

20.

Grunfeld C, Rimland D, Gibert CL, et al. Association of upper trunk and visceral adipose tissue volume with insulin resistance in control and HIV-infected subjects in the FRAM study. J Acquir Immune Defic Syndr. 2007;46:283–90.PubMedCrossRef

21.

Albu JB, Kenya S, He Q, et al. Independent associations of insulin resistance with high whole-body intermuscular and low leg subcutaneous adipose tissue distribution in obese HIV-infected women. Am J Clin Nutr. 2007;86:100–6.PubMed

22.

Torriani M, Thomas BJ, Barlow RB, et al. Increased intramyocellular lipid accumulation in HIV-infected women with fat redistribution. J Appl Physiol. 2006;100:609–14.PubMedCrossRef

23.

Bacchetti P, Gripshover B, Grunfeld C, et al. Fat distribution in men with HIV infection. J Acquir Immune Defic Syndr. 2005;40:121–31.PubMedCrossRef

24.

Klein S, Allison DB, Heymsfield SB, et al. Waist circumference and cardiometabolic risk: a consensus statement from shaping America's health: Association for Weight Management and Obesity Prevention; NAASO, the Obesity Society; the American Society for Nutrition; and the American Diabetes Association. Diabetes Care. 2007;30:1647–52.PubMedCrossRef

25.

Plank LD. Dual-energy X-ray absorptiometry and body composition. Curr Opin Clin Nutr Metab Care. 2005;8:305–9.PubMedCrossRef

26.

Park YW, Heymsfield SB, Gallagher D. Are dual-energy X-ray absorptiometry regional estimates associated with visceral adipose tissue mass? Int J Obes Relat Metab Disord. 2002;26:978–83.PubMedCrossRef

27.

Krakauer JC, Franklin B, Kleerekoper M, et al. Body composition profiles derived from dual-energy X-ray absorptiometry, total body scan, and mortality. Prev Cardiol. 2004;7:109–15.PubMedCrossRef

28.

Carr DB, Utzschneider KM, Hull RL, et al. Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes. 2004;53:2087–94.PubMedCrossRef

29.

Marques MD, Santos RD, Parga JR, et al. Relation between visceral fat and coronary artery disease evaluated by multidetector computed tomography. Atherosclerosis. 2010;209:481–6.PubMedCrossRef

30.

• Garrabou G, Lopez S, Moren C, et al. Mitochondrial damage in adipose tissue of untreated HIV-infected patients. AIDS. 2011;25:165–70. HIV infection-related mitochondrial toxicity is associated with various important clinical consequences including lipoatrophy, proinflammatory cytokine release, and possibly premature aging. This has usually been associated with exposure to various antiretroviral drugs, especially the thymidine NRTIs. This study demonstrates that HIV itself may also have a similar effect.PubMedCrossRef

31.

Gerschenson M, Brinkman K. Mitochondrial dysfunction in AIDS and its treatment. Mitochondrion. 2004;4:763–77.PubMedCrossRef

32.

Kim MJ, Leclercq P, Lanoy E, et al. A 6-month interruption of antiretroviral therapy improves adipose tissue function in HIV-infected patients: the ANRS EP29 Lipostop Study. Antivir Ther. 2007;12:1273–83.PubMed

33.

Flint OP, Noor MA, Hruz PW, et al. The role of protease inhibitors in the pathogenesis of HIV-associated lipodystrophy: cellular mechanisms and clinical implications. Toxicol Pathol. 2009;37:65–77.PubMedCrossRef

34.

Blas-Garcia A, Apostolova N, Ballesteros D, et al. Inhibition of mitochondrial function by efavirenz increases lipid content in hepatic cells. Hepatology. 2010;52:115–25.PubMedCrossRef

35.

El Hadri K, Glorian M, Monsempes C, et al. In vitro suppression of the lipogenic pathway by the nonnucleoside reverse transcriptase inhibitor efavirenz in 3 T3 and human preadipocytes or adipocytes. J Biol Chem. 2004;279:15130–41.PubMedCrossRef

36.

Haubrich RH, Riddler SA, DiRienzo AG, et al. Metabolic outcomes in a randomized trial of nucleoside, nonnucleoside and protease inhibitor-sparing regimens for initial HIV treatment. AIDS. 2009;23:1109–18.PubMedCrossRef

37.

Boothby M, McGee KC, Tomlinson JW, et al. Adipocyte differentiation, mitochondrial gene expression and fat distribution: differences between zidovudine and tenofovir after 6 months. Antivir Ther. 2009;14:1089–100.PubMedCrossRef

38.

McComsey G, Kitch D, Sax P, et al. Central fat accumulation in ART-naive subjects randomized to ABC/3TC or TDF/FTC with ATV/r or EFV: ACTG A5224s, A substudy of ACTG A5202. Abstract 77. Presented at the 18th Conference on Retroviruses and Opportunistic Infections. Boston, MA. February 27 - March 2, 2011.

39.

Poizot-Martin I, Obry-Roguet V, Biron C, et al. Abdominal adiposity remains highly prevalent in French HIV-infected patients having initiated antiretroviral therapy after 2005. Abstract PS11/1. Presented at the 12th European AIDS Conference/EACS. Cologne, Germany. November 11–14, 2009.

40.

Carr A, Ritzhaupt A, Zhang W, et al. Effects of boosted tipranavir and lopinavir on body composition, insulin sensitivity and adipocytokines in antiretroviral-naive adults. AIDS. 2008;22:2313–21.PubMedCrossRef

41.

Moyle G, Hu W, Yang R, et al. Body Composition Changes in Treatment-Naive Patients Treated with Boosted Protease Inhibitors Plus Tenofovir/Emtricitabine: Results from the CASTLE Study Through 96 Weeks. Presented at the 12th European AIDS Conference/EACS. Cologne, Germany. November 11–14, 2009.

42.

Jemsek JG, Arathoon E, Arlotti M, et al. Body fat and other metabolic effects of atazanavir and efavirenz, each administered in combination with zidovudine plus lamivudine, in antiretroviral-naive HIV-infected patients. Clin Infect Dis. 2006;42:273–80.PubMedCrossRef

43.

McComsey G, Rightmire A, Wirtz V, et al. Changes in body composition with ritonavir-boosted and unboosted atazanavir treatment in combination with Lamivudine and Stavudine: a 96-week randomized, controlled study. Clin Infect Dis. 2009;48:1323–6.PubMedCrossRef

44.

Caron-Debarle M, Lagathu C, Boccara F, et al. HIV-associated lipodystrophy: from fat injury to premature aging. Trends in Molecular Medicine. 2010;16:218–29.PubMedCrossRef

45.

Rockstroh J, Lennox J, DeJesus A, et al. Raltegravir (RAL) demonstrates durable virologic suppression and superior immunologic response with a favorable metabolic profile through 3 years of treatment (Tx): 156 week (Wk) results from STARTMRK. Abstract 542. Presented at the 18th Conference on Retroviruses and Opportunistic Infections. Boston, MA. February 27-March 2, 2011.

46.

Jacobson DL, Knox T, Spiegelman D, et al. Prevalence of, evolution of, and risk factors for fat atrophy and fat deposition in a cohort of HIV-infected men and women. Clin Infect Dis. 2005;40:1837–45.PubMedCrossRef

47.

Galli M, Veglia F, Angarano G, et al. Gender differences in antiretroviral drug-related adipose tissue alterations. Women are at higher risk than men and develop particular lipodystrophy patterns. J Acquir Immune Defic Syndr. 2003;34:58–61.PubMedCrossRef

48.

Zanone Poma B, Riva A, Nasi M, et al. Genetic polymorphisms differently influencing the emergence of atrophy and fat accumulation in HIV-related lipodystrophy. AIDS. 2008;22:1769–78.PubMedCrossRef

49.

• Crum-Cianflone N, Roediger MP, Eberly L, et al. Increasing rates of obesity among HIV-infected persons during the HIV epidemic. PLoS One. 2010;5:e10106. HIV-infected persons are not immune to the effects of increased caloric intake and decreased physical activity resulting in increased rates of overweight and obesity that are prevalent in the general population. This will impact on the higher rates of metabolic complications already occurring in these persons.PubMedCrossRef

50.

Wunder DM, Bersinger NA, Fux CA, et al. Hypogonadism in HIV-1-infected men is common and does not resolve during antiretroviral therapy. Antivir Ther. 2007;12:261–5.PubMed

51.

Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.PubMedCrossRef

52.

Llewellyn DJ, Lang IA, Langa KM, et al. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med. 2010;170:1135–41.PubMedCrossRef

53.

Kayaniyil S, Vieth R, Harris SB, et al. Association of 25(OH)D and PTH with metabolic syndrome and its traditional and nontraditional components. J Clin Endocrinol Metab. 2011;96:168–75.PubMedCrossRef

54.

Young KA, Engelman CD, Langefeld CD, et al. Association of plasma vitamin D levels with adiposity in Hispanic and African Americans. J Clin Endocrinol Metab. 2009;94:3306–13.PubMedCrossRef

55.

Brown TT. Screening and Treating HIV-Infected Patients for Vitamin D Deficiency. Clinical Care Options. HIV Journal Options 2010;6.

56.

• Stanley TL, Grinspoon SK. GH/GHRH axis in HIV lipodystrophy. Pituitary. 2009;12:143–52. This is a key article reviewing the biology of altered GH secretion in HIV lipodystrophy. The rationale for treating fat accumulation is explained and successful treatment results are consistent with the expected improvement in GH dynamics.PubMedCrossRef

57.

Stanley TL, Joy T, Hadigan CM, et al. Effects of switching from lopinavir/ritonavir to atazanavir/ritonavir on muscle glucose uptake and visceral fat in HIV-infected patients. AIDS. 2009;23:1349–57.PubMedCrossRef

58.

Ferrer E, Rio LD, Martinez E, et al. Impact of Switching from Lopinavir/Ritonavir to Atazanavir/Ritonavir on Body Fat Redistribution in Virologically Suppressed HIV-Infected Adults. AIDS Res Hum Retroviruses 2011.

59.

Kohli R, Shevitz A, Gorbach S, et al. A randomized placebo-controlled trial of metformin for the treatment of HIV lipodystrophy. HIV Med. 2007;8:420–6.PubMedCrossRef

60.

Mulligan K, Khatami H, Schwarz JM, et al. The effects of recombinant human leptin on visceral fat, dyslipidemia, and insulin resistance in patients with human immunodeficiency virus-associated lipoatrophy and hypoleptinemia. J Clin Endocrinol Metab. 2009;94:1137–44.PubMedCrossRef

61.

Bhasin S, Parker RA, Sattler F, et al. Effects of testosterone supplementation on whole body and regional fat mass and distribution in human immunodeficiency virus-infected men with abdominal obesity. J Clin Endocrinol Metab. 2007;92:1049–57.PubMedCrossRef

62.

Kotler DP, Muurahainen N, Grunfeld C, et al. Effects of growth hormone on abnormal visceral adipose tissue accumulation and dyslipidemia in HIV-infected patients. J Acquir Immune Defic Syndr. 2004;35:239–52.PubMedCrossRef

63.

Grunfeld C, Thompson M, Brown SJ, et al. Recombinant human growth hormone to treat HIV-associated adipose redistribution syndrome: 12 week induction and 24-week maintenance therapy. J Acquir Immune Defic Syndr. 2007;45:286–97.PubMed

64.

Lo J, You SM, Canavan B, et al. Low-dose physiological growth hormone in patients with HIV and abdominal fat accumulation: a randomized controlled trial. JAMA. 2008;300:509–19.PubMedCrossRef

65.

Koutkia P, Canavan B, Breu J, et al. Growth hormone-releasing hormone in HIV-infected men with lipodystrophy: a randomized controlled trial. JAMA. 2004;292:210–8.PubMedCrossRef

66.

Falutz J, Allas S, Kotler D, et al. A placebo-controlled, dose-ranging study of a growth hormone releasing factor in HIV-infected patients with abdominal fat accumulation. AIDS. 2005;19:1279–87.PubMedCrossRef

67.

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

68.

Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357:2359–70.PubMedCrossRef

69.

Falutz J, Potvin D, Mamputu JC, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension. J Acquir Immune Defic Syndr. 2010;53:311–22.PubMedCrossRef

70.

Falutz J, Mamputu JC, Potvin D, et al. Effects of Tesamorelin (TH9507), a Growth Hormone-Releasing Factor Analog, in Human Immunodeficiency Virus-Infected Patients with Excess Abdominal Fat: A Pooled Analysis of Two Multicenter, Double-Blind Placebo-Controlled Phase 3 Trials with Safety Extension Data. J Clin Endocrinol Metab. 2010;95:4291–304.PubMedCrossRef

71.

Clayton PE, Banerjee I, Murray PG, et al. Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nat Rev Endocrinol. 2011;7:11–24.PubMedCrossRef

72.

Popovic V, Mattsson AF, Gaillard RC, et al. Serum insulin-like growth factor I (IGF-I), IGF-binding proteins 2 and 3, and the risk for development of malignancies in adults with growth hormone (GH) deficiency treated with GH: data from KIMS (Pfizer International Metabolic Database). J Clin Endocrinol Metab. 2010;95:4449–54.PubMedCrossRef

73.

Theratechnologies Inc. Egrifta™ (tesamorelin for injection): US prescribing information [online]. (Available from URL: http://www.accessata.fda.gov/drugsatfda_docs/label/2010/022505s0001b1. [Accessed 2011 Jun 2].)

Title: Management of Fat Accumulation in Patients with HIV Infection
Author: Julian Falutz
Publication date: 01-09-2011
Publisher: Current Science Inc.
Published in: Current HIV/AIDS Reports / Issue 3/2011
Print ISSN: 1548-3568
Electronic ISSN: 1548-3576
DOI: https://doi.org/10.1007/s11904-011-0087-3

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2011

Adding Fuel to the Fire: Alcohol’s Effect on the HIV Epidemic in Sub-Saharan Africa

Cancer Screening in Patients Infected with HIV

Improving the Diagnosis of Tuberculosis: From QuantiFERON to New Techniques to Diagnose Tuberculosis Infections

See-and-Treat Approaches to Cervical Cancer Prevention for HIV-Infected Women

Vitamin D in HIV-Infected Patients

Renal Issues in HIV Infection

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials