PI Perspective #36

October 2003     View PDF     En español

Facial and Limb Fat Loss: Lipoatrophy

Since the advent of potent anti-HIV therapy there have been increasing reports of changes in body composition among people living with HIV. These include increases in fat in various areas of the body (the stomach area, behind the base of the neck and/or breast enlargement) or decreases in body fat (in the face, arms and/or legs) and changes in the way the body processes fats (called lipids). Any combination of these conditions is called lipodystrophy. While all these conditions have been lumped together, it’s likely they are actually different syndromes which are caused by different things.

Protease inhibitors and the NRTI drug 3TC are more associated with increases in lipids and/or accumulation of body fat. NRTI drugs like AZT and particularly d4T and other similar drugs are more associated with fat loss (sometimes called facial and limb wasting or lipoatrophy). This article focuses on lipoatrophy, what is known and what can be done about it.

What causes lipoatrophy?
Lipoatrophy is believed to be caused by long-term HIV infection or as a result of taking certain anti-HIV drugs. Exactly how HIV or medications to treat HIV causes fat loss remains unknown, though some suspect damage to the energy source of cells (called mitochondria) may play a role. Use of NRTI drugs are more associated with lipoatrophy. Specific drugs may be particular culprits, such as d4T, ddI and ddC (the “d” drugs). Lipoatrophy appears to affect White men more than women and African Americans.

What can be done about lipoatrophy?
Many questions remain about lipoatrophy, how to avoid it and how to treat it if it should occur. They include:

• Can it be avoided by not using the anti-HIV medications believed to cause it?
• Can it be reversed once it has started?
• Are there benefits to switching anti-HIV therapies or taking structured therapy interruptions?
• Can cosmetic surgery (implants or injections) provide immediate, short-term or long-lasting solutions?
• The answers to these questions are taking shape as research provides clues.

Can lipodystrophy be avoided through choice of meds?
The evidence so far hints that lipoatrophy develops either slowly or more quickly depending on the choice of anti-HIV medications. Fat loss may be more rapid and noticeable with d4T, somewhat slower with ddC and ddI, but still possible with any NRTI combination. Several studies strongly suggest that combining d-drugs (d4T, ddI, ddC) can lead to faster, more extensive lipoatrophy.

One study comparing d4T, efavirenz and 3TC with tenofovir, efavirenz and 3TC showed that the people on tenofovir had on average six pounds more fat than people who took d4T. The people who took the tenofovir regimen also had larger amounts of fat just beneath the skin (called subcutaneous fat) in their arms and legs than did the d4T group after 96 weeks (about two years).

It may be possible to decrease your risk of lipoatrophy by avoiding d-drugs in your regimen, but decreased risk certainly doesn’t mean no risk. Lipoatrophy has been seen in people on a wide variety of anti-HIV drug regimens, including those not containing d-drugs as well as among people who have never taken medication at all.

The newly approved HIV medications emtricitabine and atazanavir do not appear to induce lipoatrophy in studies performed to date so reliance on d-drugs is not an automatic necessity. There is no perfect anti-HIV drug, but a very good drug not only controls HIV levels, it should also have few side effects that interfere with the quality of daily life.

Will switching therapies help once I have lipoatrophy?
Switching from a d-drug regimen may produce a gain in layers of fat just beneath the skin (when measured with sophisticated instruments), but this gain is often not obvious to a person when they look in a mirror.

One study found a difference in subcutaneous fat gain measurements (DEXA and CT scans) at one-year intervals for 61 people who switched from NRTI-containing regimens to ritonavir + indinavir + efavirenz. However, when asked to rate their fat gain in questionnaires, they did not personally notice any improvements.

In a study called MITOX, the half of the 111 volunteers with moderate to severe lipoatrophy who switched from AZT or d4T to abacavir (300mg twice a day) without changing the rest of their regimens also experienced about a 10% gain in subcutaneous fat, but did not notice their gains in the mirror. The other half of the group, who remained on their original regimens, saw no fat gains, either on test results or in the mirror. The measurements of fat gain were made over a six-month period, possibly too short a time to produce visible changes.

Two-year follow up results of the MITOX Study were presented at a Lipodystrophy Workshop in July of this year. Those who switched from AZT or d4T to abacavir had continuous limb fat gain (36% more fat). At this rate of recovery, researchers project that full fat stores would be restored after six years.

At the current time, the bottom line is that switching from therapies that may be causing lipoatrophy might have some benefit, but it may require considerable patience, possibly years, to see visible fat gains. Not everyone who switches, however, will experience fat gains in the short or the long-term, as the drugs may not be the only cause of lipoatrophy.

What about injections or implants?
A variety of proven and unproven cosmetic procedures have been tried to treat facial wasting. In general, these approaches can be divided into short-term or longer-term solutions. Short-term solutions often involve injecting materials under the skin, which may dissolve and be absorbed by the body. Longer-term solutions include more permanent implants of material or injections of substances that are not absorbed by the body.

Advocating for changes
It is particularly important to recognize that unwanted facial fat loss may have a powerful psychological impact on both adherence and self-image, and can be a significant barrier to people starting anti-HIV therapy. People who are confident of their medications are more able to take them faithfully than people who fear their effects.

Facial restoration procedures are considered cosmetic and are not covered by insurance. Some women who have had radical mastectomies have seen insurance reimbursement; arguments for reimbursement for facial reconstruction are therefore possible based on prior practices. Nelson Vergel at the AIDS advocacy organization PoWer can be contacted through www.facialwasting.org or by phone at 713-520-6630 for information about advocacy efforts to see insurance reimbursement for facial wasting corrective procedures. For more information on lipoatrophy, call Project Inform’s Hotline.

Other Resources
A review of cosmetic approaches for treating facial wasting is available at www.facialwasting.org.

Short-Term Solutions
Collagens (Zyderm, Zyplast, Resoplast) and hyaluronic acid products (Restylane, Perlane, Macrolane) are biodegradable and their benefits can disappear over time. Costs range from $250–500 and many are not FDA-approved. Some are only available outside the U.S. Collagen removed from one’s own skin can be harvested and re-injected for anywhere from $1,000–4,000. Private insurance coverage does not extend to these procedures nor does Medicare/Medicaid reimburse for them.

Liposuction of fat from one body area to relocate the fat in facial creases is another option, but this fat may be quickly reabsorbed or migrate away from the facial area.

Longer-Term Solutions
A group of collagen implants made from tissue of dead people (Dermalogen, Fascian, AlloDerm, Cymetra) may be grafted into folds and deep wrinkles. These implants may help induce collagen to collect around the implant to render the augmentation more permanent than other collagens, which are derived from animal tissue. They are also more expensive, running into thousands of dollars. Soft implants made of man-made materials such as Goretex, Fibrel and Dermalogen are other longer-term solutions. In both these cases the body can reject the implants. Solid cheek implants of silicone or Goretex fibers should be used with caution, since they may show through the skin if the loss of facial fat is too pronounced.

Silicone gels and oils are not dissolved and absorbed by the body, but are known to relocate. They also involve risks of ongoing and visible inflammation (called granulomas). Silicone gels and oils lack FDA approval for facial wasting. However, LIS (liquid injectable silicone) and Silikon-1000 (microspheres of polymers) have been used at a physician’s prerogative with some success, particularly when granuloma formation is closely monitored and infections are promptly treated to avoid scarring. Bioform (a polysaccharide gel) and BioAlcamid (polyalkylamide gel) are other man-made preparations that could be used for correcting facial changes. Costs average around $4,000, and often require traveling outside the U.S. to obtain the products.

A skin (dermal) graft involves taking skin from another area of the body and tailoring it to restore facial fullness is another surgical option. Facelifts vary widely in cost and effect, and can provide a long-term solution for changes from lipoatrophy.

Teflon paste and bioplastics produce very problematic inflammatory reactions and serious infections and are probably poor choices.

A study of one man-made preparation, New-Fill (polylactic acid), for facial wasting is underway at Blue Pacific Aesthetic Medical Group in Hermosa Beach, CA. Up to six treatments are done at three-month intervals; six-month and twelve-month follow ups are planned. They can be contacted by phone at 310-374-0347 or online at www.bpacific.com. Conant Medical Group in San Francisco is also planning a study of New-Fill; contact Chris Eden at 415-255-0744.

New-Fill can be obtained at the same price range as BioAlcamid and Bioform, and is available through DAAIR, Direct Access Alternative Information Resources at 119 West 23rd Street, Suite #404, New York, New York 10011; call 212-255-9280, fax 212-255-9355, or email info@daair.org. Use of this product is supported by positive reports at the 2000 International Workshop on Adverse Drug Reactions in Lipodystrophy and HIV and at the Second European Workshop on Lipodystrophy.

Reyataz

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