Researchers Disprove 'Fat Redistribution Syndrome' Among Men Taking HIV Drugs

"There isn't a shred of evidence that HIV-positive men who lose fatin their legs reciprocally gain fat in their bellies," stated principalinvestigator Carl Grunfeld, MD, a staff physician at SFVAMC. "The twoare totally dissociated."

The multi-center study appears in the October 2005 issue of the Journal of Acquired Immune Deficiency Syndromes.

In their study, the authors reference 22 previously publishedpeer-reviewed papers that posit the existence of "lipodystrophy" or"fat redistribution syndrome," in which HIV therapy supposedly leads toan increase in visceral fat, or fat inside the abdomen -- which isassociated with an increased risk of cardiovascular disease -- alongwith a concomitant loss of fat in the face and limbs.

The syndrome is known among AIDS patients and care providersas "Crix belly," after the HIV drug Crixivan. "Changes in fatstigmatize HIV-infected patients and have led patients to stop theirantiretroviral therapy," write the authors.

In fact, said Grunfeld, the study of 425 HIV-positive men and152 HIV-negative controls showed that overall, HIV-positive men wholost fat in the face, arms, and legs also lost fat in the trunk -- thebelly, neck, and shoulders.

"Central fat loss and peripheral fat loss are statisticallyassociated in HIV-positive men on retroviral therapy," said Grunfeld,who is also a professor of medicine at UCSF.

Thirty-eight percent of HIV-positive men lost fat from theirfaces, arms, legs, or buttocks, compared to 5 percent of the controls;8 percent of HIV-positive men lost fat from their trunks, compared to 3percent of the controls.

Central fat gain was also less among HIV-positive men. Only 40percent of HIV-positive men gained belly fat, while 56 percent ofHIV-negative men gained belly fat.

Among both HIV-positive men who had increased visceral fat, agewas the factor most strongly associated with the increase, according tothe study. The older the man, the more likely he had high visceral fat.

This association should not be surprising, according toGrunfeld. "Age is known to be the strongest determinant of visceralfat," he noted. "These were men in middle age. Many had been sick for adecade or so. Then they got treated with decent therapy thatreconstituted their immune systems, dropped their viral load, and gotthem healthy again. Along with that, they had onset of middle-agedproblems." Grunfeld said the study results are important for severalreasons. First is the knowledge that "HIV drugs are associated with theloss of subcutaneous fat. They're not associated in men with anincrease in visceral fat."

Second, "Once we know this, we know how to counsel patients andteach physicians. We know which drugs are problematic, and how to avoidproblems. And we know to tell patients that exercise reduces visceralfat."

Finally, Grunfeld noted that although the antiretroviral drugstaken by men in the study are starting to fall out of use in the UnitedStates and other wealthy nations, one in particular -- Stavudine -- isstill commonly prescribed elsewhere in the world.

"Stavudine is being used in most AIDS drug regimens innon-industrialized Third World nations," he said. "We expect to beseeing a lot of this same fat-loss syndrome there."

Study participants were aged 33 to 45 at the time the studybegan. Fat loss or gain was determined through three methods:self-reporting, medical examination, and whole-body analysis withmagnetic resonance imaging.

Grunfeld stressed that the questionnaire used in the study forboth self-reporting and medical examination was open-ended: it askedwhether there had been a change in fat in a particular area, and if so,whether there had been a gain or a loss. This format, he said,eliminated potential bias on the part of the participant or examiner,in contrast most to previous studies, which only inquired about loss inthe peripheral areas and gain in the central areas.

Grunfeld also emphasized that unlike earlier studies, thecurrent study did not use comparison groups with the same body massindex, or BMI, because BMI is determined by muscle and fat. Since thestudy was measuring fat, "you can't adjust for something that isaffected by the very thing that you're studying." Instead, theresearchers used MRI data to determine and then adjust for lean bodymass for each subject.

Currently, Grunfeld and his fellow researchers are analyzing data from the same study for women.

For the future, predicted Grunfeld, there will be more papersbased on the study, including some dealing with the relationshipbetween HIV and risk of cardiovascular disease.

Other authors of the study were Peter Bacchetti, PhD, of UCSF;Phyllis Tien, MD, of SFVAMC and UCSF; Barbara Gripshover, MD, of CaseWestern Reserve University; Michael Saag, MD, of the University ofAlabama at Birmingham; Steven Heymsfield, MD, of St. Lukes-RooseveltHospital, New York; Michael Shlipak, MD, of SFVAMC and UCSF; DennisOsmond, PhD, of UCSF; and Heather McCreath, PhD, of UAB at the time ofthe study.

The research was funded by grants from the National Institutes ofHealth that were administered by the Northern California Institute forResearch and Education.

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