This article will briefly cover the ongoing research into the causes and possible treatments for lipoatrophy in general. It will also focus on newly approved and experimental facial fillers and implants.

What Is Facial Wasting?

Facial wasting is one symptom of a syndrome called lipoatrophy, which describes the loss of the soft layer of fat that sits just beneath the skin (subcutaneous fat). When a person has lipoatrophy, it is most noticeable in the legs, butt, arms and face. There is no single identified cause for lipoatrophy. The evidence collected so far shows that both HIV itself and the drugs used to treat it can lead to this kind of fat loss.

There are currently no proven treatments or strategies that consistently lead to restoration of fat, but there are a growing number of facial fillers and implants that can improve a person's appearance and quality of life. Sometimes people see improvements in symptoms of lipoatrophy upon changing anti-HIV regimens and reducing use of specific drugs most associated with the syndrome (e.g., stavudine). Doctors have also reported on rare cases where symptoms of lipoatrophy improved without explanation.

What Causes Lipoatrophy?

While many in the U.S. consider fat a dirty word, it actually plays a role in the function of many of our bodies' systems. It produces chemicals that talk to the immune and digestive systems and can cause the body to release or stop making certain hormones. Like every other cell in the body, fat cells require their own type of fuel to live and function. This fuel is produced and turned into energy by tiny structures inside of cells called mitochondria. When mitochondria become damaged or can't reproduce, a cell will cease working properly and eventually die.

Shortly after protease inhibitors were introduced in 1996 and 1997, doctors began to see a growing number of people on treatment who were losing fat in their arms, legs and faces, while simultaneously gaining a hard, dense kind of fat in the belly and behind the neck. This redistribution of fat became known as lipodystrophy, and protease inhibitors were blamed.

Since that time, it has been shown that nearly all anti-HIV drugs can contribute at least somewhat to many of the factors associated with changes in fat, including elevated cholesterol and reduced insulin sensitivity, though not all drugs contribute equally. A few studies have also found increased levels of fat cell death specifically among people on protease inhibitor combinations.

However, most scientists now believe that lipoatrophy occurs primarily because the fuel source (mitochondria) in fat cells becomes damaged and stops reproducing. It is likely that mitochondrial damage to other kinds of cells, notably liver cells, contributes to lipoatrophy as well. A number of studies have identified three factors associated with both mitochondrial damage and lipoatrophy:

  • long-term use of nucleoside analog anti-HIV drugs -- particularly stavudine and to a lesser degree zidovudine;

  • being over 40 years of age; and

  • having elevated triglycerides

Studies show that a person possessing all three risk factors has a higher risk for lipoatrophy than a person with only one or two. However, the studies have varied so much in their methods for measuring fat losses or gains that they cannot easily be compared. It is therefore very difficult to predict risks for developing lipoatrophy.

When it does occur, and particularly when facial wasting is more extreme, lipoatrophy can negatively affect a number of different areas of a person's life, including: self confidence; the desire to participate in social activities; sex drive; emotional well-being; the willingness or ability to adhere to treatment, and a commitment to staying on treatment. All of these are symptoms of depression, which itself is more common in people living with HIV. Some of the symptoms listed above can also be a sign of depleted testosterone levels. Anyone experiencing these symptoms consistently for more than several days in a row should be assessed and treated, if indicated, for both depression and low testosterone.

Treatment for Lipoatrophy

Before considering treatment for lipoatrophy or facial wasting, it is important to distinguish lipoatrophy from wasting syndrome. While lipoatrophy describes the loss of subcutaneous fat, wasting syndrome describes the loss of both fat and muscle mass. The most general sign of wasting syndrome is an unintended loss of more than 10% of a person's body weight, usually in combination with 30 days or more of either diarrhea or weakness, and fever. While lipoatrophy is not inherently a sign of disease progression, wasting syndrome typically is. Therefore, anyone with a progressive loss of fat in the face and limbs should be screened for wasting syndrome as well as lipoatrophy.

As discussed in the rosiglitazone article, there are currently no drugs approved to treat the underlying causes of lipoatrophy. However, studies have found that people with lipoatrophy who are taking a regimen with stavudine can often reverse fat loss to some degree by swapping it with abacavir. Studies indicate that switching from stavudine to tenofovir may produce similar results.

Glitazones, a type of drug used to treat type 2 diabetes have also shown some promise. However, none of these approaches has led to dramatic and noticeable cosmetic improvements in facial wasting. There are, however, a number of facial fillers and implants that can be used to improve the appearance of people who have lost facial fat.

Facial Fillers and Implants

Plastic surgeons and dermatologists have tried a variety of facial fillers and implants to address facial wasting cosmetically. Until August 2004, however, none of these had been extensively studied or approved by the FDA for treating this condition. Rather, they are products and techniques adapted from other uses such as standard cosmetic surgery and facial reconstruction due to injury.

In August 2004, the FDA approved Sculptra (a poly-L lactic acid, formerly known as New-Fill) for the restoration and/or correction of the signs of facial fat loss due to HIV-related lipoatrophy. The company, Dermik Aesthetics, filed for approval based on European studies in 278 people with severe lipoatrophy. The majority of the people studied were Caucasian men aged 41-45 years, nearly all of whom were on anti-HIV therapy.

People received three to six rounds of Sculptra treatment, consisting of multiple small injections, at two-week intervals. Volunteers were then monitored for two years. Roughly 40% of people studied had a significant lasting increase in the volume of tissue in the cheeks for up to two years following the series of injections. Quality of life measures (i.e., anxiety and depression surveys) also improved significantly.

Sculptra causes scar tissue and fat to collect in the areas where it is injected. The amount of Sculptra injected and method and placement of each injection can strongly impact the results, and requires proper training to achieve the best results. It can cause very small lumps called micronodules to form in up to 44% of people receiving it. The micronodules are not usually visible or the source of ongoing inflammation and infection -- as with other types of injectable fillers -- but they can often be felt under the skin.

Although most doctors use a numbing agent like lidocaine when injecting Sculptra, there is usually mild to moderate pain during the injections. Sculptra can also cause tenderness, swelling and bruising at the site of injection. This typically goes away within days.

The level of fullness resulting from each round of injections can vary from person to person. As well, people with more extreme facial wasting will sometimes require more than six rounds of injections to achieve lasting results. There are few data on the long-term use of Sculptra, or specifically on its use in women and people with darker skin.

The FDA placed two conditions on Sculptra's approval. First, the company may not encourage its use for cosmetic purposes in people not infected with HIV (e.g., to fill in wrinkles). The company also agreed to conduct an open-label study of 100 volunteers for five years to evaluate Sculptra's long-term safety. The study will include at least 30 women and 30 people with dark skin types.

Other Products

It is highly encouraging that a product has now received FDA approval specifically for facial wasting in HIV. However, Sculptra, which produces effects lasting on average for 18-24 months, represents only a moderate improvement over other types of biodegradable fillers, whose effects usually disappear in less than six months. Therefore, some plastic surgeons prefer to use permanent fillers like artificial microspheres that are coated in collagen (Artecoll) or silicone microdroplets (various products). However, none of the semi-permanent or permanent fillers are approved by the FDA for HIV-related facial wasting, and data on their use is limited and short-term.

Currently, silicone is only approved to treat retinal detachments and hemorrhages. However, the FDA allows plastic surgeons and dermatologists to use any FDA-approved product or device if the provider believes that it can effectively treat a person's medical complaint. However, a doctor may not market their use of an off-label product, so finding a doctor with enough experience with silicone may be difficult. Artecoll is not currently approved by the FDA, so treatment requires traveling to Canada or another country.

As with Sculptra, both kinds of treatment require expert application. Most experienced surgeons and dermatologists build up the sunken area with multiple tiny injections over many weeks. This is crucial as too much too soon can result in a lumpy appearance, especially if there is further fat wasting beneath and around the areas of the injections. People considering permanent fillers should consider their risks and limitations carefully and thoroughly confirm the experience of the prospective doctor with the product. Failure to do so can increase risks of serious infection and disfigurement.

All artificial implant products can cause an allergic reaction in a small percent of people. The products can also migrate from the area where they were initially implanted. Serious infection and inflammation can occur at the injection site and chronic long-term inflammation and infection are possible in up to three percent of cases.

The use of silicone for implantation was banned in the U.S. for several years because of research suggesting the development of auto-immune disorders in women whose silicone breast implants had leaked. These data were never confirmed by studies, however, and plastic surgeons have gradually begun using silicone implantation products again.

There are a small number of confirmed cases where silicone injections caused late-forming granulomas. These granulomas, which can appear many years after the injections, can be disfiguring, cause serious infections and be very difficult to treat. Thus, there remain a number of unknown and long-term risks associated with silicone. Experience with Artecoll in Canada indicates that it may be less likely to cause granulomas than silicone. However, there are no long-term data in people with HIV.

There are other treatments than those mentioned here. These treatments include collagen, fat harvesting, hyaluronic acids, polylactic acids other than Sculptra, and permanent implants of materials like Gore-Tex. However, they are typically used less often, either because they are less effective, not available in the U.S. or are most useful in rarer circumstances.

Access to Treatment

Accessing treatment for facial wasting is perhaps the greatest hurdle for people with the condition. Neither insurance companies nor government health programs will typically cover the cost of any cosmetic procedure, regardless of the impact a condition may have on a person's quality of life. Therefore, the only way for most people to access treatment is by out-of-pocket payment or by enrolling in a study.

The least expensive fillers, such as collagen, start at around $200 per vial of the product. Products like Sculptra can cost up to $500 per vial, and the most expensive permanent fillers cost in excess of $100 per vial. The amount needed for a treatment can vary a great deal depending on the degree of wasting that has occurred. One vial is typically the minimum used per round of injections. An additional charge will also be the fees of the doctor administering the injections. These charges can vary, but are typically up to $500 or more per round of injections. Since most treatments for facial wasting require a minimum of four rounds of injections, the total cost of treatment often exceeds $6,000.

Doctors and activists are advocating with the makers of Sculptra to form a patient assistance program (PAP) for people who cannot afford the cost of treatment. Even if a Sculptra PAP is formed, however, this will not cover the cost of the injection procedure. Therefore, AIDS activists are also working with policy experts to determine whether programs like Medicaid or ADAP may be able to cover these costs in some circumstances. However, at a time when the escalating costs of drugs are stretching healthcare systems to the breaking point, this is likely to be a challenge.


Dealing effectively with facial wasting can be a serious challenge. There's still much to be learned and limited options. As with any treatment decision, however, it all comes back to making a series of decisions and taking action wherever possible. The first step is to avoid or stop using the drugs most likely to contribute to lipoatrophy. The second step involves ruling out any other potential causes of fat wasting.

If facial wasting becomes particularly troublesome, and you have the resources, it may be worthwhile to discuss alternatives with a highly experienced practitioner -- one who has experience treating HIV-related facial wasting. Choosing the right doctor is critical. For those who do not have the resources, studies may be available near you.

Back to the Project Inform Perspective November 2004 contents page.