Gone All Pear-Shaped?

BY HIV Plus Editors

September 01 2010 12:00 AM ET

Even five years after switching to newer medications, HIVers who lost subcutaneous fat as a result of taking first-generation anti-HIV meds still show strikingly less body fat than seronegative individuals, according to a study published in the July 17 issue of the journal AIDS. That lack of fat ' just below the layer of skin ' was marked in HIVers' legs and lower trunk, where body fat is associated with a lower risk of cardiovascular disease ' but less so in the visceral, or deep, fat and upper-body fat associated with increased cardiovascular risk.

'This shows that the damage done by certain antiretroviral drugs, which were lifesaving at the time but reduced body fat, is long-term,' says Carl Grunfeld, MD, Ph.D., who is chief of the metabolism and endocrine sections at the San Francisco Veterans Affairs Medical Center, which conducted the study with the University of California, San Francisco. 'This is the first study to demonstrate that the effect lasts at least five years.'

The study authors twice measured total body fat among 477 HIV-infected participants and 214 noninfected control subjects. The first measurement was taken between 2000 and 2002, when most people in the United States with HIV were taking drug combinations that included the fat-toxic drugs stavudine and zidovudine. The second measurement was taken five years after the first, by which time most patients had been switched to modern highly active antiretroviral therapy, which has not been shown to destroy body fat. The researchers found that at both the first and second measurements, the HIVers in the study had significantly less body fat, especially lower body fat, than the control participants.

The difference in upper-body fat was much smaller, says Grunfeld: 'The worst initial loss was in the best fat, and the least loss was in the worst fat. Five years later at the second measurement the HIV-infected patients had gained very little lower body fat.' The result, he says, is increased risk of cardiovascular disease among HIVers.

There are several reasons for the increased cardiovascular disease risk, explains Grunfeld, who is also a professor of medicine at UCSF. Upper-body fat is known to be associated with elevated insulin resistance and high blood triglycerides ' two known heart disease risk factors ' while lower-body fat is associated with decreased insulin resistance and lower triglycerides.

In addition, HAART is known to be associated with increased triglycerides, as is HIV itself. 'It all adds up to bad cardiovascular-disease risk for HIV-infected people,' Grunfeld says. 'Furthermore, it's a risk that is probably not going to go away. Patients and physicians need to be aware of it ' and take whatever other steps they can to reduce that risk.'

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