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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 metabolic effects usually associated with the lipodystrophy syndrome include:
- Fat redistribution, including lipohypertrophy (viscera, breast, neck) and lipoatrophy (subcutaneous fat).
- Insulin resistance (hyperglycaemia).
- Dyslipidaemia (raised total cholesterol and triglycerides, lowered high-density lipoprotein (HDL) cholesterol).
It may coexist 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 dyslipidaemia is common with PI's occurring in between 27% and 40% as compared with 8% in age matched, treatment naive HIV infected patients. Stavudine was most strongly associated with dyslipidaemias.
- Insulin resistance is common and diabetes mellitus occurred in 7% of patients with lipoatrophy in one study, some 14 times higher than in the healthy matched control group.
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 lipodystrophy syndrome in HIV patients (LDHIV). A prevalence of 33% has been quoted for highly active antiretroviral treatment (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:
- 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 lipodystrophy syndrome in HIV patients (LDHIV). Efforts in this direction are being targeted on:
- Increasing awareness amongst doctors and patients, together with regular assessment, 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 antiretroviral treatment (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.
Lipodystrophy in primary care
Primary care physicians will very often not be involved with the detailed management of their patients with HIV. They may feel threatened by their patients' own high level of knowledge. However, time spent learning about HIV has potential for great benefit. It extends and improves the network of informed support. For example:
- It improves scope for psychological support.
- It improves awareness of adverse effects such as lipodystrophy syndrome in HIV patients (LDHIV), allowing earlier detection.
- It supports and helps to reinforce lifestyle changes.
- It may prompt timely referral for management of metabolic changes, dyslipidaemias, lipodystrophy, corrective procedures, etc.
- It may help adherence levels and cardiovascular risk management. This may, in turn, ultimately improve long-term survival.
Further reading & references
- Guidelines for the treatment of HIV-infected adults with antiretroviral therapy, The British HIV Association (2008)
- Management of sexually transmitted infections and related conditions in children and young people, British Association for Sexual Health and HIV (2010)
- Nolan D, Reiss P, Mallal S; Adverse effects of antiretroviral therapy for HIV infection: a review of selected topics. Expert Opin Drug Saf. 2005 Mar;4(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 Feb;18(1):55-8.
- Das S; HIV and increased risk of cardiovascular diseases. Sex Health. 2005;2(4):219-21.
- GB guidelines: British HIV Association (BHIVA) Guidelines for HIV treatment, 2005
- Robles DT et al; Lipodystrophy, HIV, eMedicine, Dec 2008
- Krause JC, Toye MP, Stechenberg BW, et al; HIV--associated lipodystrophy in children. Pediatr Endocrinol Rev. 2005 Sep;3(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 Jan;53(1):15-25.
- 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 Jul;6(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 Mar;38(3):411-7.
- Mauss S; Prevention and therapy of HIV-associated lipodystrophy syndrome and antiretroviral caused metabolic changes. MMW Fortschr Med. 2005 Apr 25;147 Spec No 1:49-53.
- Jones D; HIV facial lipoatrophy: causes and treatment options. Dermatol Surg. 2005 Nov;31(11 Pt 2):1519-29; discussion 1529.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
Dr Richard Draper
Dr Richard Draper
Dr Helen Huins