Lipodystrophy Syndrome

The lipodystrophy syndrome (LDHIV) associated with antiretroviral treatment for the human immunodeficiency virus (HIV) infection has been the subject of intense research in recent years.¹

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 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 stigmatizing. It has a significant adverse effect on quality of life.²
• 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.³
• The adverse effect on adherence. This 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 analogues (NRTIs) are implicated, but patients who have never had either have been reported with the syndrome.⁴
• Certain antivirals for HIV are associated with a higher relative risk of 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.⁴
• The dyslipidaemia is common with PI's occurring in between 27% and 40% as compared to 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.⁴

Prevalence

The prevalence in adults varies from 2-60% but for UK adults a recent paper quotes a prevalence of 17%.⁵ With increased awareness there are now fewer new cases of LDHIV.⁴ A prevalence of 33% has been quoted for HAART (Highly active antiretroviral treatment) treated HIV children.⁶

Risk factors

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 caucasions.⁵

The disease is progressive, becoming more noticeable with duration of disease and length of treatment. The disfigurement can be distressing and stigmatizing.
The following physical changes may occur:

• Fasting lipid profile (hyperlipidaemia e.g. if TC>5.5 mmol/L and TG>2mmol/L).
• Fasting glucose (impaired fasting glycaemia if 6.1-7mmol/L or diabetic over 7 mmol/L).
• MRI can be used to demonstrate visceral fat in the abdomen.⁷

Prevention

It is important having identified aetiological factors to try and prevent 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.⁷
• 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.⁴
• Earlier treatment of the HIV infection, may help prevent LDHIV (before AIDS develops and before the CD4 count falls below 200/mm³).⁴

Treatments

It is important that patients are 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.⁸ A Mediterranean diet, high in omega 3, high in fresh fruit vegetables and fibre is generally recommended.⁴ Exercise is also recommended although consistent changes in plasma lipids will not be seen in the short term.⁹
• Other measures to improve metabolic parameters.
  • Metformin may improve the lipids and studies are being undertaken on the glitazones.⁴
  • 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 contraindicated because of PI drug interactions. Pravastatin is the most studied.⁴ Patients should be referred to a lipid specialist.
• Modifying the ART treatment regimen. Decisions should be taken carefully as this may risk long term survival. Unfortunately there is little evidence on which to base decisions.¹⁰ It may improve the lipodystrophy detectable using imaging techniques but it is not known how durable these changes are.⁴ Generally speaking switching from thymidine analogues (d4T, ZDV) to ABC or TDF has some effect on lipodystrophy.⁴
• Corrective procedures. The adverse effects on quality of life, social withdrawal and psychological distress of particularly facial lipoatrophy has led to use of skin fillers and implants by plastic surgeons, dermatologists and ENT surgeons. Some have tried implanting autologous fat cells. The longer lasting (poly-L-lactic acid and silicone based) are favoured over absorbable fillers.¹¹ Surgery is not an option for the abdominal lipohypertrophy.⁴

Primary care physicians will very often not be involved with the detailed management of their patients with HIV. They may feel threatened by the 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 LDHIV allowing earlier detection.
• It supports and helps 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.