Of all the tongue-twisting medical terms that have entered HIVers' vocabularies, few have caused more grief than "lipoatrophy," which is the loss of fat from specific areas of the body -- most distressingly the face, but also peripheral parts of the body, such as the arms, legs and buttocks. This side effect has presented HIV-positive people with profound social and psychological challenges. (For a fast 411, see "Lipoatrophy at a Glance." To get definitions of key buzzwords, see "Lipoatrophy Buzzwords.")
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The loss (i.e., the "atrophy") of subcutaneous fat (fat underneath the skin) is related to several other common problems that people with HIV confront. Although the smoking gun is most likely specific HIV medications, the actual bullet is what doctors call a metabolic complication. Metabolic complications are problems that your body may develop in the way it creates, stores and uses energy, such as by digesting the food you eat.
These are some of the symptoms that may indicate that HIV meds are messing with your body's metabolism:
- Lipodystrophy, or changes in body shape and appearance, including lipoatrophy (fat loss) and lipohypertrophy (fat accumulation)
- A sudden increase in lipid levels (cholesterol and triglycerides), which can raise your risk for heart disease
- Blood sugar problems, including diabetes, insulin resistance and glucose intolerance
- Bone and joint problems, such as osteoporosis, osteopenia and osteonecrosis
- Lactic acidosis, or an increased concentration of lactic acid in the blood
The way some HIV meds are believed to cause lipoatrophy is like this: Research has shown that three drugs in particular -- d4T (stavudine, Zerit), AZT (zidovudine, Retrovir) and ddI (didanosine, Videx) -- can damage tiny structures, called mitochondria, inside your fat cells. Mitochondria are tiny powerplants that convert nutrients, such as sugars and fats, into energy necessary for the cell to function. By blocking the production of an enzyme that mitochondria need in order to reproduce, HIV meds can cause more and more of a fat cell's mitochondria to fail, cutting off the cell's energy source. This has been proven with d4T, although there are less data to show this is true about AZT and ddI. Over time, that fat-cell loss becomes all too visible as lipoatrophy. (Researchers don't yet know whether the fat cells die outright or are just disabled. If they're disabled, it may mean that they can recover -- albeit oh-so-slowly -- when the drug causing the problem is stopped.)
When they first appeared in the 1990s, the symptoms of lipoatrophy were often confused with AIDS-related wasting syndrome, once a telltale signal of advanced HIV disease. In fact, the two conditions are extremely different: While lipoatrophy targets only fat cells in specific parts of the body, AIDS wasting destroys fat and muscle from all over the body. Moreover, while people with lipoatrophy typically have low viral loads because their HIV is being successfully suppressed by HIV medications, people with AIDS-related wasting are losing body weight because of the immune destruction caused by rampant viral replication.
Initially, many experts also mixed up lipoatrophy with lipohypertrophy, or fat accumulation, which was most commonly seen in the belly, back or (in women) breasts. How could fat loss be confused with its opposite? Because both conditions first appeared around the same time -- in the 1990s -- and often in the same person, leading some to believe that they were part of the same syndrome.
HIVer Jane (not her real name), for instance, started taking AZT + 3TC (lamivudine, Epivir) + indinavir (Crixivan) in 1995, and soon began to lose fat in her legs and forearms at the same time as she was rapidly gaining weight in her torso and belly. "I went from an A [bra] cup to a C cup in two months," she recalls. The strange fat gains and losses gave her body an out-of-proportion appearance. At the time, Jane believed she had what doctors were then mistakenly diagnosing as a bizarre "reshuffling" of the body's fat, rather than the two distinct conditions that are now known.
Lipohypertrophy's lumps, humps and bumps are more accurately diagnosed these days than they were when Jane first developed symptoms, but the cause(s) remains somewhat controversial. Most researchers agree that lipohypertrophy, like lipoatrophy, is likely the side effect of HIV drugs, but which meds and why are harder to pinpoint. Other theories include the familiar "it's-caused-by-interactions-between-drugs" idea and the more novel "it's-caused-by-the-immune-boosting-effects-of-treatment" argument. Future research, let's hope, will unlock lipohypertrophy's mysteries.
Meanwhile, in addition to Jane's body-shape changes, her total cholesterol steadily rose, topping out at a dangerous 350 -- another of the metabolic complications we now associate with some HIV meds. When she switched to a new combo in 2002, her cholesterol dropped like a rock and her lipohypertrophy markedly reversed. Diet and exercise have also helped.
Unfortunately, Jane's peripheral lipoatrophy is still stubbornly visible. "Sometimes I look at my skinny legs and fat belly and see proof of the disease," Jane says. "But I always try to change that perspective to proof that I'm surviving."
When lipoatrophy first appeared in the late '90s -- not long after the debut of combination HIV therapy, which brought many an ailing "Lazarus" back from death's door -- many doctors were slow to take the problem seriously. Some dismissed their patients' complaints as a matter of vanity: After all, wasn't "puppet face," as it was dubbed with typical HIVer black humor, a small price to pay for the fact that these new drugs gave people lifesaving control over the deadly bug?
Even physicians of a more sensitive stripe had difficulty facing the cruel irony that, as the University of North Carolina at Chapel Hill's Dr. David Wohl says, "The medications [that] were helping people to survive ... were also disfiguring them." As Dr. Wohl recalls, though, the distorting effects of lipoatrophy soon became undeniable: "I used to say I could go to our waiting room and tell which patients were taking Zerit just by looking at their faces."
For people who were suddenly faced with losing their face, lipoatrophy raised the issue of quality of life in an unprecedented way. For the first time, HIV treatment wasn't just about surviving. As the century turned, many began to ask: Was feeling better physically worth the loss of not only their looks, but also a key to their sense of self?
As the condition struck more and more HIVers -- causing fat to dissolve from faces, cheeks to go gaunt, deep folds to form around noses and mouths, temples and eye sockets to hollow out -- it fast replaced AIDS wasting and Kaposi's sarcoma lesions as the cause of the dreaded "AIDS look." As with any stigma, this development sometimes had devastating emotional consequences.
Many people with HIV met the challenge defiantly, wearing their lipoatrophy with a warrior's pride. A mild case of lipoatrophy could give a face a much-prized "chiseled" look; legs and arms could take on a gym-toned appearance.
But lots of others with severe lipoatrophy experienced a serious erosion of self-esteem and self-confidence; even their very identity suffered when they saw the sick-looking, aging, alien face in their mirror.
"Friends kept asking me if I was losing weight or feeling unwell," recalls long-time HIV treatment activist Nelson Vergel, who experienced what he describes as a mild case of lipoatrophy while taking d4T. "It was really bothering me because the meds were making me feel better than I had in a long time."
Equally troubling, facial lipoatrophy "outed" some people as having HIV at a time when, or in a place where, disclosure was not an option -- sometimes triggering rejection and discrimination and worse. In an e-mail interview, this gay man in his 30s, who asked to remain nameless, voiced the despair that facial lipoatrophy can trigger:
"I try my best not to let it bother me, but it's not easy. In my day I was considered something of a 'looker.' Now I feel that when people look at me, it's because I'm a car wreck and not because I'm cute. Now I am the person that is often the subject of malicious gossip. Now I am a 'faggot with AIDS.' Not that I have AIDS [I only have HIV], but the way my face looks instantly gives that impression. Even my 'own people,' other gays, shun me. I have no social life. Would it have been better to have already died of this virus, or is it better that I have gone through the maze that is HIV management to live this lonely and depressing life?"
(For many different perspectives on lipoatrophy, check out our interviews with HIVers and with doctors. The interview with Dr. Bob Frascino, who is both an HIVer with lipo and an AIDS specialist, is especially enlightening. You can also download podcasts of all of these interviews.)
Although lipoatrophy, in itself, isn't known to pose any serious health risks, it nonetheless quickly became known as the side effect from hell. It even caused some HIVers to vow that they would never start treatment, and caused some of those who were already on treatment to stop taking their meds -- sometimes without even telling their doctors. It was actually these red flags that finally made physicians and researchers spring into action, plumbing the mysteries of this fat-loss effect.
Over the past several years, researchers have narrowed the list of lipoatrophy culprits down to three major offenders:
- d4T, which has the most research proving that it does the most lipo damage
- AZT (also a part of the combination drugs Combivir and Trizivir), which can cause fat loss, but at a considerably slower rate than d4T. Research is not as strong regarding fat loss and AZT.
- ddI, which may do the dirty deed only when taken with d4T -- a common '90s combo
Some researchers also point to protease inhibitors -- especially ritonavir (Norvir)-boosted combos -- as possible lipo-causing suspects, because lab tests have shown conclusively that they cause the breakdown of fat cells. Dr. Kathleen Mulligan, an experienced HIV researcher who focuses on body-shape problems, notes that the protease link hasn't just been found in the lab. "Several clinical studies, including one I was involved with, suggest that the addition of a protease inhibitor can accelerate lipoatrophy," she says. One study has also found that combining d4T with certain protease inhibitors caused greater loss of fat than taking d4T sans a protease inhibitor.
Of course, keep in mind that not everyone on these drugs is heading for a fat fall. Plenty of folks on AZT and ddI are doing just fine, thank you, as are tons of people taking protease inhibitors. Plus, the wrinkles and bags in that reflection in the mirror may have nothing to do with meds or HIV. Just because HIVers already have so many other issues to deal with does not mean they are exempt from the insults and problems of aging.
In fact, various studies indicate that there are numerous secondary factors that likely contribute to the development of lipoatrophy. They include the effects of HIV itself as well as aging, genetic predisposition, CD4 count at the time a person starts HIV treatment (the lower the count the higher the risk may be) and the length of time on treatment (the longer you've been on treatment the higher the risk may be).
So, if you want to avoid lipoatrophy, what can you do about it? The truth is, you may not have to do much at all: Many of the meds that have been most associated with lipoatrophy, like d4T, aren't used that much in the United States anymore, thanks to the development of newer, safer meds in recent years.
"I have lots of patients with lipoatrophy, but they're all people who've been on therapy since back in the 20th century," says Dr. Joel Gallant, director of Johns Hopkins Hospital's Moore HIV Clinic. "I'm not seeing the new development of lipoatrophy anymore, because we now have better treatment options."
By just saying no to the drugs that cause fat loss, newbies to HIV treatment may be able to skirt med-related fat loss altogether. That means avoiding d4T, and perhaps also ddI and AZT, in favor of equally effective nucleoside analogs such as abacavir (Ziagen), Epzicom (abacavir/3TC, Kivexa), tenofovir (Viread) and Truvada (tenofovir/FTC) should steer you clear of fat loss, since they're kinder and gentler on your mitochondria (although keep in mind that no drug is side effect free).
But what if you're on HIV treatment and you think your body is showing signs of lipoatrophy: What options do you have? The first thing to do -- before you even consider stopping your meds -- is to have a heart-to-heart with your HIV doc. Stopping meds without warning can potentially lead to resistance, which is bad news (The Body's special report on resistance has plenty more info on this subject). If you're on a combination containing d4T, you can talk to your doctor about switching to a fat-friendlier nucleoside analog or another class of meds. The urgency about switching from AZT or ddI is less clear. Of course, if you're treatment experienced and are resistant to many drugs, you may have little choice but to take some of these lipo-causing meds, which, aside from their side effects, are actually quite powerful meds -- or to seek out a clinical trial of a new drug in development.
Still, keep in mind that when it comes to reversing lipoatrophy, there's no miracle cure -- at least not one that we know of yet. Research has shown that switching from d4T or AZT to a more fat-friendly drug, like abacavir or tenofovir, can arrest lipo's development -- and may even help those damaged fat cells begin to make a comeback. But it's an extremely slow recovery.
And of course, the decision to change a regimen that is successfully keeping your HIV in check is a serious one, miserable side effects or not. So -- once again -- be sure to talk over the pluses and minuses with your doctor. Keep in mind that every HIV med can have complications, so you may be exchanging one set of side effects for another -- or the devil you know for the devil you don't.
Once you've switched to a new combo, you can be reasonably confident that you've put the brakes on the vanishing fat. But reversing the process is another matter; as we just noted, the body's natural recovery of fat may be excruciatingly slow. As a result, many people with facial lipoatrophy decide to have plastic surgery, also known as "reconstructive procedures" or "facial fillers," in order to restore their face to its normal appearance.
All facial fillers work in essentially the same way: They replace the fat you've lost by adding material to the space right beneath the skin. None of them can cure lipoatrophy; they "merely" mask the symptoms -- which, for many people, is just what the doctor ordered.
The main differences among facial fillers lie in the type of substance being injected into the skin (natural or synthetic), the length of time that it lasts (temporary or permanent) and, of course, the cost (high or higher). You can compare many of these fillers side by side by giving our chart a gander.
Although there are many fillers out there, only two products -- Sculptra (poly-L-lactic acid, New-Fill) and Radiesse (calcium hydroxylapatite, Radiance) -- are approved to treat lipoatrophy in people with HIV in the United States. That means they are the only facial fillers that have a reasonable chance of being covered by your health insurance.
Unfortunately, even though Sculptra and Radiesse are approved medications in the United States, the majority of insurance carriers still see them as cosmetic treatments, so you may be in for a long, hard fight with your insurance company to get them to foot the bill. There are two important facts that argue in HIVers' favor, however: 1) lipoatrophy can cause crippling psychological (and sometimes physical) effects; and 2) the procedure "reconstructs" your face to "normal" rather than cosmetically enhancing it beyond what it was. (For more on how to get reconstructive surgery covered by insurance, click here.) So don't give up: Your persistence may pay off, and even if you lose, the more HIVers who demand a change in policy, the harder it will be for the insurance industry to assert that the procedure is purely cosmetic.
Although there are many reconstructive treatments available for the symptoms of lipoatrophy, few show much promise as cures for the underlying cause: mitochondrial toxicity. Two drugs that have been used for insulin resistance in type 2 diabetes, rosiglitazone (Avandia) and pioglitazone (Actos), are at the top of most researchers' wish lists. But so far their actual effectiveness in restoring fat cells has proved pretty modest, especially in people who were on d4T for a long period of time. Uridine is a naturally occurring nucleoside available commercially in the supplement called NucleomaxX, a sugar-cane extract, that has some researchers excited because it appears to help in overcoming mitochondrial toxicity. Meanwhile, research into the mitochondrial mystery is moving forward.
Even in the absence of a "cure," the war against lipoatrophy has largely been won. We now know how to prevent it by avoiding certain meds. And we have the means, if not always the money, to correct severe cases.
For those like Jeff Berry who are learning to live with lipoatrophy -- and struggling to come to terms with what he calls "the death of my face" (see his column, "About Face") -- we hope that our Lipoatrophy Resource Center will offer not only information on possible strategies to combat lipoatrophy, but inspiration, support and a critical reminder that you are not alone. As cliché as it may sound, it truly is what's on the inside that counts.
Open Clinical Trials
Want to help find out which treatments for lipoatrophy work? Join a clinical trial!
More Information on Diagnosis and Treatment
Check out The Body's main lipoatrophy page, where you'll find more personal accounts and information about diagnosis and treatment.
Ask the Experts
You can browse a collection of facial wasting questions and answers from The Body's experts. Or you can post your own question in our forums on facial wasting or managing side effects.
Keep an eye on The Body's conference coverage -- you never know what kind of interesting lipoatrophy research may be presented.
Lipoatrophy Mailing List
If you want to talk to other HIVers about their experience with facial fillers, join PWA (person with AIDS) activist Nelson Vergel's e-mail list.
Offers lipoatrophy research, an overview of reconstructive procedures, a message board and further resources.
Dermik Laboratories -- The Maker of Sculptra
If you're interested in Sculptra treatments, visit Dermik's Sculptra Web site.
For more on body shape changes in general, check out this in depth interview with patient advocate Nelson Vergel and researcher Donald Kotler, M.D.
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