Fat Chance

A Treatment for Lipodystrophy-Related Excessive Abdominal Fat Comes of Age
by Chael Needle

HIV-associated lipodystrophy, abnormalities in metabolism and/or distribution of fat in those living with HIV/AIDS on antiretrovirals, sometimes is characterized by excess abdominal fat.

The FDA recently approved a new drug, Egrifta (tesamorelin for injection), that has been shown to reduce excess abdominal fat associated with lipodystrophy in HIV-positive patients. The first and only treatment indicated for this condition, Egrifta is a synthetic analogue of growth hormone releasing factor that acts on the pituitary cells in the brain to stimulate synthesis and release of endogenous growth hormone. FDA approval was based on two multicenter, randomized, double-blind, placebo-controlled Phase III studies that enrolled 816 HIV-positive patients with lipodystrophy-related excess abdominal fat.

Some of the side effects noted so far are possible fluid retention, glucose intolerance, and hypersensitivity reactions. Patients with active malignancies should wait until those are treated before weighing the risks and benefits of Egrifta.

Asked if there is a basic profile for who might be a good candidate for Egrifta, David Wohl, MD, associate professor of medicine, University of North Carolina at Chapel Hill, responds, “The profile is very similar if not identical to those who were enrolled in the study. Wisely, the studies were designed to look at who might most benefit from the product: individuals who have excess abdominal fat and lipodystrophy with HIV infection.” A treating physician, Dr. Wohl served as a coinvestigator at one of the many sites that participated in the Egrifta study that led to its FDA approval.

Lipodystrophy is defined not only by changes in fat but changes in metabolism that negatively affect health. The study was designed, however, to focus on excess abdominal fat. “Having a big belly is associated with [negative health complications] and we know this largely from studies of HIV-uninfected people.…But there’s nothing we can do right now to connect the dots to say, ‘Take this and your heart disease is going to get better,’ for instance,” says Dr. Wohl. “We know visceral fat is metabolically active, so I think there’s a role for studying whether or not reducing [this type of fat] leads to other outcome benefits beyond reduction in that fat volume. But I think that has to be seen.”

When asked, Dr. Wohl agrees that diet and exercise would be a logical complement to Egrifta. “We all want a magic pill or magic shot and I stress to people that there’s no such thing. It would be great if we had something that would melt fat away, but it does take work. There are data from research, albeit from smallish studies, that show that diet and exercise do have a benefit and can reduce excess fat in the belly, both subcutaneous and deep-down fat. Both can be reduced by a pretty rigorous but reasonable regimen of diet and exercise.”

Moderation is key when it comes to diet, he adds. “Try not to make cookies and cake a recommended daily allowance but for special occasions!” As for exercise, anarobic and aerobic conditioning is a good starting-point.

Diet and exercise “are interventions that we know do lead to better outcomes vis-a-vis cardiovascular disease, diabetes prevention, and longevity. So it just makes sense to start with those things. This again is something that’s really geared toward answering the question, ‘Can we help people who despite all their best efforts, despite their condition, or who maybe can’t exercise because of neuropathy, maybe this is something we can give to people to maybe help alleviate their distress.”

Looking into whether Egrifta’s benefits outweigh any risks comes down to patient-physician conversation.

“We’re talking about something that has to do with your body shape and the question, ‘Is it worth it for you to take a medication, to inject that medication, to maybe have to deal with some side effects, because it’s not completely inert, to see your belly fat reduced? For many of my patients, they’re going to say, ‘Absolutely yes.’ But some people may say, ‘Well, I don’t know, maybe I’ll try to do something else or maybe I’ll just hit the gym more or maybe I’ll just live with it.”

Ultimately, reducing excess fat is not a cosmetic decision. Dr. Wohl agrees. “It has to do with the way you feel—the way you feel as far as your attractiveness, the way you feel when trying to bend down and tie your shoes, the discomfort that people sometimes feel when they roll over in bed. This is more than just the way you look or the way your clothes fit. This has a lot to do with self-esteem, body image, disclosure of your HIV status. For those who’ve never had to deal with this, it may be hard to understand but anyone who’s spoken to someone who’s living with lipodystrophy will get it in a nanosecond—why it’s really important to try to help folks live a long time, not looking like they came from [MTV’s] Jersey Shore, but just looking more normal….”

All of this potential means little, says Dr. Wohl, without reducing the barriers to access. “I think there’s a challenge for the community—for the pharmaceutical community, the advocacy community, patient community, medical community—to make sure that people who need this drug and can benefit from it gain access to it. And that’s true for all different therapeutics in HIV.”

Chael Needle wrote about repositioning anti-cancer drugs in the fight against HIV in the December 2010 issue.

January 2011