Lipodystrophy is the term given to describe a series of changes in body composition [loss of fat in the legs, arms, or face, breast enlargement, central obesity (sometimes called protease paunch), dorsal fat pads (known as buffalo hump), etc.] as well as changes in laboratory markers associated with how the body processes fats and sugars (e.g., cholesterol and triglyceride changes, also called lipids). Several new findings were recently reported at the 3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV. Although these results may help in making decisions about specific therapies, they offer little information on the cause of lipodystrophy syndromes. However, several studies to be presented at the Conference on Retroviruses and Opportunistic Infections in February 2002 may shed more light on the cause and will be reported on in the next PI Perspective.

Cosmetic Surgery for Facial Wasting: New-Fill Injections

Results from a French study of New-Fill (polylactic acid) shows that it may help increase the thickness of the cheek fat pad and other places where fat loss is sometimes apparent. Some people have experienced lipoatrophy (fat loss), which is believed to be associated with anti-HIV therapy and in particular the nucleoside analogue (NRTI) drugs. This study involved four injections of New-Fill (3cc in each cheek) at days 0, 15, 30 and 45. A fifth injection was given at day 60 if there was inadequate response.

Fifty people participated and all began the study with a marked and visible reduction in fat tissue in the cheeks (sunken cheeks) as measured by ultrasonography (using ultrasound technology to produce an image). At the time of the report, four people had received three injections, 29 had four injections and 17 had five. All volunteers had a dramatic improvement, with the majority regaining fat tissue in the cheeks. Some participants experienced a slight swelling at the injection site.

The manufacturer claims that New-Fill does not directly fill the spaces left empty by lipoatrophy. Rather, the product is claimed to build or grow a matrix under the skin which is then filled in by the body's own production of collagen.

New-Fill is not currently approved by the FDA and is not commonly available to physicians. For a time, the product was being imported from France for personal use, but in recent months the FDA blocked bulk importation of the product, arguing that the product should be classified as a "device" rather than a drug or natural supplement. The agency feels it is thus not subject to the personal importation rules for drugs. Still some people are successfully bringing back personal supplies of New-Fill from Tijuana, Mexico.

Discussions with the FDA are ongoing, looking for a way to make the product available to people in need while further studies are designed. A major problem is that the supplier is a small company that does not have the resources to conduct clinical trials. Some dermatologists offer products they claim are similar, and a few clinics near the Mexican border treat patients with New-Fill or similar products.

Facial lipoatrophy many not be physically harmful, but it can add a serious psychological burden for people with HIV infection. Although New-Fill has not been proven to be effective, neither has it shown any serious toxicity to date. Project Inform supports the right of people with HIV to have access to this and similar products.

Human Growth Hormone and Lipodystrophy

A study of five people has shown that human growth hormone (Serostim) can decrease triglyceride and cholesterol levels (decrease in LDL or bad cholesterol and increase in HDL or good cholesterol). It was, however, associated with development of insulin resistance that led to increased glucose production (a condition associated with diabetes). The dose used in this study was 3 mg/day. Similar to results from a previous study, participants experienced a loss in fat and gain in lean tissue. People considering using human growth hormone should also consider having a glucose tolerance test done before starting the drug. Future studies using lower doses are planned.

Do Some Therapies Pose More of a Threat?

Interim analysis of one study shows that different anti-HIV regimens may have different effects on cholesterol and triglyceride levels. This study enrolled 258 people (half were women), all of whom had not taken anti-HIV therapy before. The average viral load at study entry was about 30,000 copies and the average CD4+ cell count was about 350. Volunteers received abacavir/Combivir (Combivir is AZT/3TC), nelfinavir/Combivir or d4T/3TC/nelfinavir.

After 24 weeks, there were no differences in anti-HIV activity among the three groups, with 49-59% of the participants experiencing viral load suppression to under 400 copies. However, there were major differences in triglyceride and cholesterol levels among them. People on the nelfinavir combinations saw their cholesterol levels substantially increase compared to those on abacavir who only had a slight increase. However, only people taking d4T/3TC/nelfinavir had substantial increases in triglyceride levels while the other two groups only had minor increases. Cholesterol and triglyceride increases have been associated with lipodystrophy in some people. The study had not yet run long enough to know whether any particular regimen was more likely to result in fat loss or redistribution.

Amprenavir and Lipodystrophy

A small intensive monitoring study shows that amprenavir can greatly increase triglyceride and cholesterol levels, contrary to earlier reports that it does not affect these lipid markers. This study enrolled 16 people, all of whom had not previously taken a protease inhibitor, abacavir, d4T or 3TC. During the study, the volunteers received abacavir/3TC/amprenavir (two people used d4T instead of 3TC).

Overall there were no major changes in laboratory markers for diabetes, including fasting glucose and fasting insulin levels. There was, however, a decrease in insulin sensitivity after 48 weeks, but not before. People experienced a progressive increase in markers of fat processing, triglyceride levels and cholesterol levels. The good news is that HDL (good) cholesterol increased as well as LDL (bad) cholesterol resulting in no change in the overall ratio of HDL/LDL. The ratio of HDL to LDL may be even more important than the actual levels.

Additionally, participants saw an increase in weight, trunk fat and limb fat resulting in an overall increase in total body fat. There was also a trend towards an increase in lean tissue. One interesting observation is that insulin resistance developed after weight gain. This can potentially help in better understanding how the lipodystrophy syndromes occur.

Back to the Project Inform Perspective March 2002 contents page.