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Lipodystrophy is a medical condition characterised by complete or partial loss of adipose tissue. Complete or partial loss of fat (lipoatrophy) may occur in conjunction with pathological accumulation of fat in other distinct regions of the body. Metabolic abnormalities, including insulin resistance, diabetes mellitus, hypertriglyceridaemia, and hepatic steatosis, are frequently associated with lipodystrophy. The extent of fat loss determines the severity of associated metabolic complications.
The lipodystrophies can be divided into generalised, partial or local, depending on the degree and locality of the observable fat loss.
- Fat redistribution, including lipohypertrophy (central) and lipoatrophy (predominantly face and lower limbs).
- Insulin resistance (hyperglycaemia).
- Dyslipidaemia (raised total cholesterol and triglycerides, lowered high-density lipoprotein (HDL) cholesterol).
The lipodystrophy syndrome associated with antiretroviral treatment (ART) for the human immunodeficiency virus (HIV) infection has been the subject of intense research in recent years.
The rest of this article deals with HIV-related lipodystrophy.
HIV lipodystrophy may co-exist with other metabolic disorders associated with long-term HIV infection, such as raised serum lactate, reduced bone mineral density, hypogonadism and hypertension. It is important because:
- The physical changes are obvious and can have many psychologically damaging effects. The condition identifies patients with HIV infection and is thus stigmatising. It has a significant adverse effect on quality of life.
- The associated metabolic changes may threaten long-term survival. The management of risk factors for cardiovascular disease is an increasingly important part of the management of HIV infection.
- The adverse effect on adherence may compromise management of the HIV infection.
The aetiology is unknown and explanations uncertain and speculative.
- A number of factors have been identified as important in cross-sectional studies and it is likely to be caused by an interaction between the HIV infection, the immune recovery and the antiretroviral medication. Both protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitor (NRTI) analogues are implicated, but patients who have never had either have been reported with the syndrome.
- Certain antivirals for HIV are associated with a higher relative risk of lipodystrophy syndrome in HIV patients (LDHIV). The highest prevalence is in those who have had PIs and NRTIs together. The highest relative risk is associated with stavudine (d4T) especially if given with didanosine (ddI). Zidovudine (ZDV) is also strongly associated with lipodystrophy syndrome.
The prevalence in adults varies from 2-60% but for UK adults a recent paper quotes a prevalence of 17%. With increased awareness there are now fewer new cases of LDHIV. A prevalence of 33% has been quoted for highly active antiretroviral therapy (HAART) treated HIV children.
An increased risk of LDHIV is associated with:
- Duration of disease.
- Gender. Women are at higher risk of LDHIV than men.
- Length of treatment and particularly with PIs as described above.
- Race. Lipoatrophy is more common in Caucasians.
The disease is progressive, becoming more noticeable with duration of disease and length of treatment. The disfigurement can be distressing and stigmatising.
The following physical changes may occur:
- Development of a 'buffalo hump' or increased dorso-cervical fat pad.
- Expansion of neck circumference by up to 10 cm.
- Breast hypertrophy.
- Central truncal adiposity caused by visceral fat accumulation ('protease paunch')
- Loss of subcutaneous fat from face, arms, shoulders, buttocks, thighs etc.
- Prominence of veins.
- An emaciated appearance.
- Anorexia nervosa.
- Cancer cachexia.
- Severe chronic infection.
- Adrenal insufficiency.
- Fasting lipid profile (hyperlipidaemia - eg, if total cholesterol (TC) >5.5 mmol/L and triglyceride (TG) >2 mmol/L).
- Fasting glucose (impaired fasting glycaemia if 6.1-7 mmol/L or diabetic over 7 mmol/L).
- MRI can be used to demonstrate visceral fat in the abdomen.
It is important, having identified aetiological factors, to try to prevent LDHIV. Efforts in this direction are being targeted on:
- Increasing awareness amongst doctors and patients, together with regular assessment, which may help early identification. Early identification may be assisted by techniques such as MRI.
- Choice of antiretroviral regimen, avoiding combinations of PIs and certain NRTIs.
- Early treatment and interventions for metabolic changes (as these may promote the LDHIV).
- General advice on diet and exercise. This may include use of supplements, high fibre, and omega 3, etc.
- Earlier treatment of the HIV infection, may help prevent LDHIV (before AIDS develops and before the CD4 count falls below 200/mm3).
It is important that patients should be adequately assessed. Treatment can be divided into:
- Lifestyle modification (smoking, diet, exercise). A diet with high protein, trans-fat and less fibre in patients on PIs was linked with LDHIV. A Mediterranean diet, high in omega 3, fresh fruit and vegetables and fibre, is generally recommended. Exercise is also recommended although consistent changes in plasma lipids will not be seen in the short term.
- Other measures to improve metabolic parameters:
- Metformin may improve the lipids and studies are being undertaken on the glitazones.
- Growth hormone has been tried for the lipodystrophy but is expensive and there is a risk of hyperglycaemia.
- Statins and fibrates improve the dyslipidaemia but not the lipodystrophy. Simvastatin is contra-indicated because of PI drug interactions. Pravastatin is the most studied. Patients should be referred to a lipid specialist.
- Modifying the ART regimen. Decisions should be taken carefully, as changes may affect long-term survival. Unfortunately, there is little evidence on which to base decisions. It may improve the lipodystrophy detectable using imaging techniques but it is not known how durable these changes are. Generally speaking, switching from thymidine analogues (d4T, ZDV) to abacavir (ABC) or tenofovir DF (TDF) has some effect on lipodystrophy.
- Corrective procedures. The adverse effects on quality of life, social withdrawal and psychological distress, particularly of facial lipoatrophy, have led to use of skin fillers and implants by plastic surgeons, dermatologists and ear, nose and throat (ENT) surgeons. Some have tried implanting autologous fat cells. The longer-lasting (poly-L-lactic acid- and silicone-based) are favoured over absorbable fillers. Surgery is not an option for the abdominal lipohypertrophy.
Further reading and references
Management of sexually transmitted infections and related conditions in children and young people; British Association for Sexual Health and HIV (2010)
Garg A; Clinical review#: Lipodystrophies: genetic and acquired body fat disorders. J Clin Endocrinol Metab. 2011 Nov96(11):3313-25. doi: 10.1210/jc.2011-1159. Epub 2011 Aug 24.
Fiorenza CG, Chou SH, Mantzoros CS; Lipodystrophy: pathophysiology and advances in treatment. Nat Rev Endocrinol. 2011 Mar7(3):137-50. doi: 10.1038/nrendo.2010.199. Epub 2010 Nov 16.
Huang-Doran I, Sleigh A, Rochford JJ, et al; Lipodystrophy: metabolic insights from a rare disorder. J Endocrinol. 2010 Dec207(3):245-55. doi: 10.1677/JOE-10-0272. Epub 2010 Sep 24.
Nolis T; Exploring the pathophysiology behind the more common genetic and acquired lipodystrophies. J Hum Genet. 2014 Jan59(1):16-23. doi: 10.1038/jhg.2013.107. Epub 2013 Oct 24.
Leung VL, Glesby MJ; Pathogenesis and treatment of HIV lipohypertrophy. Curr Opin Infect Dis. 2011 Feb24(1):43-9. doi: 10.1097/QCO.0b013e3283420eef.
Alves MD, Brites C, Sprinz E; HIV-associated lipodystrophy: a review from a Brazilian perspective. Ther Clin Risk Manag. 2014 Jul 1710:559-66. doi: 10.2147/TCRM.S35075. eCollection 2014.
Nolan D, Reiss P, Mallal S; Adverse effects of antiretroviral therapy for HIV infection: a review of selected topics. Expert Opin Drug Saf. 2005 Mar4(2):201-18.
Nicholas PK, Kirksey KM, Corless IB, et al; Lipodystrophy and quality of life in HIV: symptom management issues. Appl Nurs Res. 2005 Feb18(1):55-8.
Das S; HIV and increased risk of cardiovascular diseases. Sex Health. 20052(4):219-21.
Krause JC, Toye MP, Stechenberg BW, et al; HIV--associated lipodystrophy in children. Pediatr Endocrinol Rev. 2005 Sep3(1):45-51.
Dinges WL, Chen D, Snell PG, et al; Regional body fat distribution in HIV-infected patients with lipodystrophy. J Investig Med. 2005 Jan53(1):15-25.
Vantyghem MC, Balavoine AS, Douillard C, et al; How to diagnose a lipodystrophy syndrome. Ann Endocrinol (Paris). 2012 Jun73(3):170-89. doi: 10.1016/j.ando.2012.04.010. Epub 2012 Jun 28.
Chu C, Selwyn PA; Complications of HIV infection: a systems-based approach. Am Fam Physician. 2011 Feb 1583(4):395-406.
Shah M, Tierney K, Adams-Huet B, et al; The role of diet, exercise and smoking in dyslipidaemia in HIV-infected patients with lipodystrophy. HIV Med. 2005 Jul6(4):291-8.
Terry L, Sprinz E, Stein R, et al; Exercise training in HIV-1-infected individuals with dyslipidemia and lipodystrophy. Med Sci Sports Exerc. 2006 Mar38(3):411-7.
Mauss S; Prevention and therapy of HIV-associated lipodystrophy syndrome and antiretroviral caused metabolic changes. MMW Fortschr Med. 2005 Apr 25147 Spec No 1:49-53.
Jones D; HIV facial lipoatrophy: causes and treatment options. Dermatol Surg. 2005 Nov31(11 Pt 2):1519-29