No shred of evidence that HIV-positive men who lose fat in their legs reciprocally gain fat in their bellies

Oct 13 2005

There is no syndrome that causes increased belly fat and decreased facial and limb fat among HIV-positive men who take antiretroviral drugs, according to a study by researchers at the San Francisco VA Medical Center and the University of California, San Francisco.

"There isn't a shred of evidence that HIV-positive men who lose fat in their legs reciprocally gain fat in their bellies," stated principal investigator Carl Grunfeld, MD, a staff physician at SFVAMC. "The two are 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 published peer-reviewed papers that posit the existence of "lipodystrophy" or "fat redistribution syndrome," in which HIV therapy supposedly leads to an increase in visceral fat, or fat inside the abdomen -- which is associated with an increased risk of cardiovascular disease -- along with a concomitant loss of fat in the face and limbs.

The syndrome is known among AIDS patients and care providers as "Crix belly," after the HIV drug Crixivan. "Changes in fat stigmatize HIV-infected patients and have led patients to stop their antiretroviral therapy," write the authors.

In fact, said Grunfeld, the study of 425 HIV-positive men and 152 HIV-negative controls showed that overall, HIV-positive men who lost fat in the face, arms, and legs also lost fat in the trunk -- the belly, neck, and shoulders.

"Central fat loss and peripheral fat loss are statistically associated 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 their faces, arms, legs, or buttocks, compared to 5 percent of the controls; 8 percent of HIV-positive men lost fat from their trunks, compared to 3 percent of the controls.

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

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

This association should not be surprising, according to Grunfeld. "Age is known to be the strongest determinant of visceral fat," he noted. "These were men in middle age. Many had been sick for a decade or so. Then they got treated with decent therapy that reconstituted their immune systems, dropped their viral load, and got them healthy again. Along with that, they had onset of middle-aged problems." Grunfeld said the study results are important for several reasons. First is the knowledge that "HIV drugs are associated with the loss of subcutaneous fat. They're not associated in men with an increase in visceral fat."

Second, "Once we know this, we know how to counsel patients and teach physicians. We know which drugs are problematic, and how to avoid problems. And we know to tell patients that exercise reduces visceral fat."

Finally, Grunfeld noted that although the antiretroviral drugs taken by men in the study are starting to fall out of use in the United States and other wealthy nations, one in particular – Stavudine – is still commonly prescribed elsewhere in the world.

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

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

Grunfeld stressed that the questionnaire used in the study for both self-reporting and medical examination was open-ended: it asked whether 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 in the peripheral areas and gain in the central areas.

Grunfeld also emphasized that unlike earlier studies, the current study did not use comparison groups with the same body mass index, or BMI, because BMI is determined by muscle and fat. Since the study was measuring fat, "you can't adjust for something that is affected by the very thing that you're studying." Instead, the researchers used MRI data to determine and then adjust for lean body mass 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 papers based on the study, including some dealing with the relationship between 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 Case Western Reserve University; Michael Saag, MD, of the University of Alabama at Birmingham; Steven Heymsfield, MD, of St. Lukes-Roosevelt Hospital, New York; Michael Shlipak, MD, of SFVAMC and UCSF; Dennis Osmond, PhD, of UCSF; and Heather McCreath, PhD, of UAB at the time of the study.