Treatment of HIV-associated lipodystrophy

INTRODUCTION

The term HIV-associated lipodystrophy typically refers to changes in fat distribution that are often associated with metabolic abnormalities, including dyslipidemia and insulin resistance [1]. Specifically, patients with lipoatrophy have loss of subcutaneous fat, most noticeably in the limbs, face, and/or buttocks areas. Patients with fat accumulation have gain of visceral fat in the abdomen and may have dorsocervical fat pad enlargement (buffalo hump) and breast enlargement.

Patients may present with lipoatrophy, fat accumulation, or a combination of the two [2]. Since potential management differs depending on the nature of the change in fat, lipoatrophy and fat accumulation will be discussed separately after a general consideration of the rationale for treating these disorders.

The treatment of HIV-associated lipodystrophy will be reviewed here. The epidemiology, clinical manifestations, and diagnosis of lipodystrophy are discussed separately. (See "Epidemiology, clinical manifestations, and diagnosis of HIV-associated lipodystrophy".)

RATIONALE FOR TREATMENT

There are multiple reasons to consider treating HIV-associated lipodystrophy, as there are several potential benefits beyond pure cosmesis.

Metabolic derangements associated with lipodystrophy (dyslipidemia and abnormal glucose metabolism) may predispose patients to cardiovascular disease. Behavioral and medical interventions to address HIV-associated lipodystrophy have the potential to favorably affect these metabolic parameters and ultimately reduce the risk of atherosclerosis and diabetes mellitus. (See "Epidemiology, clinical manifestations, and diagnosis of HIV-associated lipodystrophy".)

                     

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Literature review current through: Oct 2014. | This topic last updated: Oct 22, 2014.
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References
Top
  1. Wohl DA, McComsey G, Tebas P, et al. Current concepts in the diagnosis and management of metabolic complications of HIV infection and its therapy. Clin Infect Dis 2006; 43:645.
  2. Bacchetti P, Gripshover B, Grunfeld C, et al. Fat distribution in men with HIV infection. J Acquir Immune Defic Syndr 2005; 40:121.
  3. Power R, Tate HL, McGill SM, Taylor C. A qualitative study of the psychosocial implications of lipodystrophy syndrome on HIV positive individuals. Sex Transm Infect 2003; 79:137.
  4. Oette M, Juretzko P, Kroidl A, et al. Lipodystrophy syndrome and self-assessment of well-being and physical appearance in HIV-positive patients. AIDS Patient Care STDS 2002; 16:413.
  5. Ammassari A, Antinori A, Cozzi-Lepri A, et al. Relationship between HAART adherence and adipose tissue alterations. J Acquir Immune Defic Syndr 2002; 31 Suppl 3:S140.
  6. Opravil M, Hirschel B, Lazzarin A, et al. A randomized trial of simplified maintenance therapy with abacavir, lamivudine, and zidovudine in human immunodeficiency virus infection. J Infect Dis 2002; 185:1251.
  7. Carr A, Workman C, Smith DE, et al. Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial. JAMA 2002; 288:207.
  8. Martin A, Smith DE, Carr A, et al. Reversibility of lipoatrophy in HIV-infected patients 2 years after switching from a thymidine analogue to abacavir: the MITOX Extension Study. AIDS 2004; 18:1029.
  9. McComsey GA, Ward DJ, Hessenthaler SM, et al. Improvement in lipoatrophy associated with highly active antiretroviral therapy in human immunodeficiency virus-infected patients switched from stavudine to abacavir or zidovudine: the results of the TARHEEL study. Clin Infect Dis 2004; 38:263.
  10. Moyle GJ, Sabin CA, Cartledge J, et al. A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy. AIDS 2006; 20:2043.
  11. Tien PC, Schneider MF, Cole SR, et al. Relation of stavudine discontinuation to anthropometric changes among HIV-infected women. J Acquir Immune Defic Syndr 2007; 44:43.
  12. Grunfeld C, Saag M, Cofrancesco J Jr, et al. Regional adipose tissue measured by MRI over 5 years in HIV-infected and control participants indicates persistence of HIV-associated lipoatrophy. AIDS 2010; 24:1717.
  13. Tebas P, Zhang J, Yarasheski K, et al. Switching to a protease inhibitor-containing, nucleoside-sparing regimen (lopinavir/ritonavir plus efavirenz) increases limb fat but raises serum lipid levels: results of a prospective randomized trial (AIDS clinical trial group 5125s). J Acquir Immune Defic Syndr 2007; 45:193.
  14. Fisac C, Fumero E, Crespo M, et al. Metabolic benefits 24 months after replacing a protease inhibitor with abacavir, efavirenz or nevirapine. AIDS 2005; 19:917.
  15. Moyle G, Baldwin C, Mandalia S, et al. Changes in metabolic parameters and body shape after replacement of protease inhibitor With efavirenz in virologically controlled HIV-1-positive persons: single-arm observational cohort. J Acquir Immune Defic Syndr 2001; 28:399.
  16. Martínez E, Conget I, Lozano L, et al. Reversion of metabolic abnormalities after switching from HIV-1 protease inhibitors to nevirapine. AIDS 1999; 13:805.
  17. Martínez E, García-Viejo MA, Blanco JL, et al. Impact of switching from human immunodeficiency virus type 1 protease inhibitors to efavirenz in successfully treated adults with lipodystrophy. Clin Infect Dis 2000; 31:1266.
  18. Moyle GJ, Andrade-Villanueva J, Girard PM, et al. A randomized comparative 96-week trial of boosted atazanavir versus continued boosted protease inhibitor in HIV-1 patients with abdominal adiposity. Antivir Ther 2012; 17:689.
  19. Funk E, Bressler FJ, Brissett AE. Contemporary surgical management of HIV-associated facial lipoatrophy. Otolaryngol Head Neck Surg 2006; 134:1015.
  20. Loutfy MR, Raboud JM, Antoniou T, et al. Immediate versus delayed polyalkylimide gel injections to correct facial lipoatrophy in HIV-positive patients. AIDS 2007; 21:1147.
  21. Cofrancesco J Jr, Brown T, Martins CR. Management options for facial lipoatrophy. AIDS Read 2004; 14:639.
  22. Burgess CM, Quiroga RM. Assessment of the safety and efficacy of poly-L-lactic acid for the treatment of HIV-associated facial lipoatrophy. J Am Acad Dermatol 2005; 52:233.
  23. Humble G, Mest D. Soft tissue augmentation using sculptra. Facial Plast Surg 2004; 20:157.
  24. Sculptra® (injectable poly-L-lactic acid) product monograph, Berwyn, PA: Dermik Laboratories, 2004 (package insert). 2004.
  25. Valantin MA, Aubron-Olivier C, Ghosn J, et al. Polylactic acid implants (New-Fill) to correct facial lipoatrophy in HIV-infected patients: results of the open-label study VEGA. AIDS 2003; 17:2471.
  26. Moyle GJ, Lysakova L, Brown S, et al. A randomized open-label study of immediate versus delayed polylactic acid injections for the cosmetic management of facial lipoatrophy in persons with HIV infection. HIV Med 2004; 5:82.
  27. Mest DR, Humble G. Safety and efficacy of poly-L-lactic acid injections in persons with HIV-associated lipoatrophy: the US experience. Dermatol Surg 2006; 32:1336.
  28. Borelli C, Kunte C, Weisenseel P, et al. Deep subcutaneous application of poly-L-lactic acid as a filler for facial lipoatrophy in HIV-infected patients. Skin Pharmacol Physiol 2005; 18:273.
  29. Bodokh I, Simonet P. [Polylactic acid injections (Newfill) in the treatment of facial lipodystrophy in HIV-positive patients]. Ann Dermatol Venereol 2006; 133:429.
  30. Cattelan AM, Bauer U, Trevenzoli M, et al. Use of polylactic acid implants to correct facial lipoatrophy in human immunodeficiency virus 1-positive individuals receiving combination antiretroviral therapy. Arch Dermatol 2006; 142:329.
  31. Moyle GJ, Brown S, Lysakova L, Barton SE. Long-term safety and efficacy of poly-L-lactic acid in the treatment of HIV-related facial lipoatrophy. HIV Med 2006; 7:181.
  32. Carey DL, Baker D, Rogers GD, et al. A randomized, multicenter, open-label study of poly-L-lactic acid for HIV-1 facial lipoatrophy. J Acquir Immune Defic Syndr 2007; 46:581.
  33. Hanke CW, Redbord KP. Safety and efficacy of poly-L-lactic acid in HIV lipoatrophy and lipoatrophy of aging. J Drugs Dermatol 2007; 6:123.
  34. Levy RM, Redbord KP, Hanke CW. Treatment of HIV lipoatrophy and lipoatrophy of aging with poly-L-lactic acid: a prospective 3-year follow-up study. J Am Acad Dermatol 2008; 59:923.
  35. Narciso P, Bucciardini R, Tozzi V, et al. Immediate versus delayed surgical intervention for reconstructive therapy of HIV-associated facial lipoatrophy: a randomized open-label study. AIDS Res Hum Retroviruses 2009; 25:979.
  36. El-Beyrouty C, Huang V, Darnold CJ, Clay PG. Poly-L-lactic acid for facial lipoatrophy in HIV. Ann Pharmacother 2006; 40:1602.
  37. Mest DR, Humble GM. Retreatment with injectable poly-l-lactic acid for HIV-associated facial lipoatrophy: 24-month extension of the Blue Pacific study. Dermatol Surg 2009; 35 Suppl 1:350.
  38. Tzikas TL. Evaluation of the Radiance FN soft tissue filler for facial soft tissue augmentation. Arch Facial Plast Surg 2004; 6:234.
  39. Comite SL, Liu JF, Balasubramanian S, Christian MA. Treatment of HIV-associated facial lipoatrophy with Radiance FN (Radiesse). Dermatol Online J 2004; 10:2.
  40. Roth JS. Restorative approaches for HIV-associated lipoatrophy. PRS Notebook 2005; 10:24.
  41. Busso M, Karlsberg PL. Cheek augmentation and rejuvenation using injectable calcium hydroxylapatite (Radiesse). Cosmet Dermatol 2006; 19:583.
  42. Silvers SL, Eviatar JA, Echavez MI, Pappas AL. Prospective, open-label, 18-month trial of calcium hydroxylapatite (Radiesse) for facial soft-tissue augmentation in patients with human immunodeficiency virus-associated lipoatrophy: one-year durability. Plast Reconstr Surg 2006; 118:34S.
  43. Carruthers A, Carruthers J. Evaluation of injectable calcium hydroxylapatite for the treatment of facial lipoatrophy associated with human immunodeficiency virus. Dermatol Surg 2008; 34:1486.
  44. Sutinen J. Interventions for managing antiretroviral therapy-associated lipoatrophy. Curr Opin Infect Dis 2005; 18:25.
  45. Nadarajah JT, Collins M, Raboud J, et al. Infectious complications of Bio-Alcamid filler used for HIV-related facial lipoatrophy. Clin Infect Dis 2012; 55:1568.
  46. Guaraldi G, Fontdevila J, Christensen LH, et al. Surgical correction of HIV-associated facial lipoatrophy. AIDS 2011; 25:1.
  47. Shuck J, Iorio ML, Hung R, Davison SP. Autologous fat grafting and injectable dermal fillers for human immunodeficiency virus-associated facial lipodystrophy: a comparison of safety, efficacy, and long-term treatment outcomes. Plast Reconstr Surg 2013; 131:499.
  48. Grinspoon S. Use of thiazolidinediones in HIV-infected patients: what have we learned? J Infect Dis 2007; 195:1731.
  49. Colmers IN, Bowker SL, Majumdar SR, Johnson JA. Use of thiazolidinediones and the risk of bladder cancer among people with type 2 diabetes: a meta-analysis. CMAJ 2012; 184:E675.
  50. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356:2457.
  51. Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 2009; 373:2125.
  52. Carr A, Workman C, Carey D, et al. No effect of rosiglitazone for treatment of HIV-1 lipoatrophy: randomised, double-blind, placebo-controlled trial. Lancet 2004; 363:429.
  53. Sutinen J, Häkkinen AM, Westerbacka J, et al. Rosiglitazone in the treatment of HAART-associated lipodystrophy--a randomized double-blind placebo-controlled study. Antivir Ther 2003; 8:199.
  54. Hadigan C, Yawetz S, Thomas A, et al. Metabolic effects of rosiglitazone in HIV lipodystrophy: a randomized, controlled trial. Ann Intern Med 2004; 140:786.
  55. Cavalcanti RB, Raboud J, Shen S, et al. A randomized, placebo-controlled trial of rosiglitazone for HIV-related lipoatrophy. J Infect Dis 2007; 195:1754.
  56. Tungsiripat M, Bejjani DE, Rizk N, et al. Rosiglitazone improves lipoatrophy in patients receiving thymidine-sparing regimens. AIDS 2010; 24:1291.
  57. Raboud JM, Diong C, Carr A, et al. A meta-analysis of six placebo-controlled trials of thiazolidinedione therapy for HIV lipoatrophy. HIV Clin Trials 2010; 11:39.
  58. Mallon PW, Sedwell R, Rogers G, et al. Effect of rosiglitazone on peroxisome proliferator-activated receptor gamma gene expression in human adipose tissue is limited by antiretroviral drug-induced mitochondrial dysfunction. J Infect Dis 2008; 198:1794.
  59. Hadigan C. Peroxisome proliferator-activated receptor gamma agonists and the treatment of HIV-associated lipoatrophy: unraveling the molecular mechanism of their shortcomings. J Infect Dis 2008; 198:1729.
  60. Slama L, Lanoy E, Valantin MA, et al. Effect of pioglitazone on HIV-1-related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113). Antivir Ther 2008; 13:67.
  61. Calmy A, Hirschel B, Hans D, et al. Glitazones in lipodystrophy syndrome induced by highly active antiretroviral therapy. AIDS 2003; 17:770.
  62. Walker UA, Auclair M, Lebrecht D, et al. Uridine abrogates the adverse effects of antiretroviral pyrimidine analogues on adipose cell functions. Antivir Ther 2006; 11:25.
  63. Sutinen J, Walker UA, Sevastianova K, et al. Uridine supplementation for the treatment of antiretroviral therapy-associated lipoatrophy: a randomized, double-blind, placebo-controlled trial. Antivir Ther 2007; 12:97.
  64. McComsey GA, Walker UA, Budhathoki CB, et al. Uridine supplementation in the treatment of HIV lipoatrophy: results of ACTG 5229. AIDS 2010; 24:2507.
  65. Lee JH, Chan JL, Sourlas E, et al. Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy. J Clin Endocrinol Metab 2006; 91:2605.
  66. 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.
  67. Roubenoff R, Weiss L, McDermott A, et al. A pilot study of exercise training to reduce trunk fat in adults with HIV-associated fat redistribution. AIDS 1999; 13:1373.
  68. Thöni GJ, Fedou C, Brun JF, et al. Reduction of fat accumulation and lipid disorders by individualized light aerobic training in human immunodeficiency virus infected patients with lipodystrophy and/or dyslipidemia. Diabetes Metab 2002; 28:397.
  69. Kohli R, Shevitz A, Gorbach S, Wanke C. A randomized placebo-controlled trial of metformin for the treatment of HIV lipodystrophy. HIV Med 2007; 8:420.
  70. Hadigan C, Meigs JB, Rabe J, et al. Increased PAI-1 and tPA antigen levels are reduced with metformin therapy in HIV-infected patients with fat redistribution and insulin resistance. J Clin Endocrinol Metab 2001; 86:939.
  71. Hadigan C, Corcoran C, Basgoz N, et al. Metformin in the treatment of HIV lipodystrophy syndrome: A randomized controlled trial. JAMA 2000; 284:472.
  72. Driscoll SD, Meininger GE, Lareau MT, et al. Effects of exercise training and metformin on body composition and cardiovascular indices in HIV-infected patients. AIDS 2004; 18:465.
  73. 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.
  74. 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.
  75. Falutz J, Allas S, Mamputu JC, et al. Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation. AIDS 2008; 22:1719.
  76. 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.
  77. 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.
  78. Stanley TL, Feldpausch MN, Oh J, 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; 312:380.
  79. Clayton PE, Banerjee I, Murray PG, Renehan AG. Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nat Rev Endocrinol 2011; 7:11.
  80. Renehan AG, Zwahlen M, Minder C, et al. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 2004; 363:1346.
  81. Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 2007; 370:59.
  82. Piliero PJ, Hubbard M, King J, Faragon JJ. Use of ultrasonography-assisted liposuction for the treatment of human immunodeficiency virus-associated enlargement of the dorsocervical fat pad. Clin Infect Dis 2003; 37:1374.
  83. Connolly N, Manders E, Riddler S. Suction-assisted lipectomy for lipodystrophy. AIDS Res Hum Retroviruses 2004; 20:813.
  84. Gervasoni C, Ridolfo AL, Rovati L, et al. Maintenance of breast size reduction after mastoplasty and switch to a protease inhibitor-sparing regimen in an HIV-positive woman with highly active antiretroviral therapy-associated massive breast enlargement. AIDS Patient Care STDS 2002; 16:307.
  85. Schambelan M, Mulligan K, Grunfeld C, et al. Recombinant human growth hormone in patients with HIV-associated wasting. A randomized, placebo-controlled trial. Serostim Study Group. Ann Intern Med 1996; 125:873.
  86. 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.
  87. 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.
  88. Lo J, You SM, Liebau J, et al. Effects of low-dose growth hormone withdrawal in patients with HIV. JAMA 2010; 304:272.