August 9, 2006 (AIDSmeds)—New data from a large study indicates that a loss of fat (lipoatrophy) is a common occurrence in HIV positive women. The women-only results from the Fat Redistribution and Metabolic Changein HIV Infection (FRAM) study, much like the FRAM study data involvingmen published in 2005, also indicate that increased fat(lipohypertrophy) is not more likely to occur in HIV-positive womencompared to HIV-negative women.

For several years,beginning with the widespread use of HIV combination therapy, differenttypes of body-shape changes – notably lipoatrophy of the face, arms,and legs, and lipohypertrophy of the abdominal area – have beenreported by numerous HIV-positive people and their healthcareproviders. In turn, they were both unofficially lumped together as asingle syndrome called “lipodystrohy,” likely caused by anti-HIV drug treatment.

Researchers,however, have long questioned if these two different types ofbody-shape changes are related. Some HIV-positive people don’t have anysigns of lipoatrophy or lipohypertrophy, some experience one or theother, whereas others experience both. Because different HIV-positivepeople seem to experience different problems, it has been difficult todetermine if either of these body-shape changes is truly a uniquecomplication caused by HIV or its treatment.

Forresearchers to understand the cause(s), prevention, and treatment ofthese complications, studies to determine if these body-shape changesare unique among HIV-positive people – and how these body-shape changesrelate to each other – have been needed.

FRAM is onesuch study. It is headed by Dr. Carl Grunfeld of the University ofCalifornia, San Francisco. Between June 2000 and September 2002, FRAMenrolled 1,480 volunteers, including 1,183 HIV-positive people and 297HIV-negative people. HIV-negative study volunteers were included forcomparison purposes. Of 1,480 enrolled, there were 350 HIV-positivewomen and 142 HIV-negative women.

The study results involving women were reported in the August 15 issue of the Journal of Acquired Immune Deficiency Syndromes. 

Muchlike the comparison between HIV-positive and HIV-negative men in FRAM,lipoatrophy was more common among the HIV-positive women compared tothe HIV-negative women. Approximately 28% of the HIV-positive women had“clinical” lipoatrophy of at least one part of the body – fat loss thatwas reported by the study participants and confirmed by the researchersduring a physical examination – compared to 4% of the HIV-negativewomen.

More HIV-positive women, compared to HIV-negativewomen, reported loss of fat in the cheeks, face, arms, buttocks, andlegs. HIV-positive women were also more likely to report a decrease intheir waist size compared to their HIV-negative counterparts.

Thestudy also demonstrated that HIV-positive women do experiencelipohypertrophy. However, clinical lipohypertrophy was just as likelyto be seen in the HIV-negative women. Approximately 62% of theHIV-positive women had lipohypertrophy of at least one part of thebody, compared to 63% of the HIV-negative women.

HIV-negativewomen were more likely to have lipohypertrophy of the cheeks, face,arms, buttocks, legs, neck, chest, and upper back. There was nostatistically significant differences between lipohypertrophy of thewaist or the abdomen in the two groups of women.

Magneticresonance imaging (MRI) data were also reported. The amount, or volume,of visceral fat – fat deep within the body that can cause the abdominalarea to appear enlarged – was significantly lower among women withclinical lipoatrophy compared to the HIV-positive women withoutlipoatrophy.

Just like the FRAM data involving men,these results indicate that for women too, lipoatrophy is a uniquecomplication caused by HIV and/or HIV medications. Similarly, FRAMsuggests that lipohypertrophy is not a unique complication of HIVinfection or HIV treatment, given that visceral fat increases were seenin a large percentage of HIV-negative women as well.

Theone major difference between the men and women in FRAM involves fataccumulation in the upper trunk (the chest and back). The women withoutclinical lipoatrophy had greater amounts of visceral fat andsubcutaneous fat – fat under the skin – in the upper trunk than theHIV-negative women. With the men, the volume of visceral andsubcutaneous fat in the upper trunk was no different in those withoutlipoatrophy compared to the HIV-negative men.

Thestudy also suggested that lipoatrophy and lipohypertrophy are notlinked – women who had increased visceral fat were more likely to haveincreased (not decreased) subcutaneous fat. In other words, FRAMsuggests that visceral fat and subcutaneous fat either increasetogether or decrease together; one doesn’t go up while the other goesdown.

As is reviewed in our lipodystrophy lesson, theFRAM results involving the male volunteers have been frustrating to anumber of people. It is likely that the newest results involving thefemale volunteers will cause equal consternation.

Acommon misperception of the FRAM study is that lipohypertrophy is not aproblem for HIV-positive men or women. However, neither the male orfemale data support this.

FRAM concludes that abnormalfat increases can and do occur in HIV-positive people, but notnecessarily to a greater extent than HIV-negative people. Nor does theFRAM study suggest that these fat increases are “healthy,” given thatthey are also seen in HIV-negative people. Numerous experts, includingthose associated with the FRAM study, stress that enlarged visceral fatdeposits are not healthy. They can cause serious problems for bothHIV-positive and HIV-negative people.

It is alsoimportant to recognize that FRAM is not a perfect study. For starters,it is a cross-sectional study. This means that the study relied on aone-time “snapshot” of all patients enrolled. Because it didn’t followthe study volunteers over time, it’s impossible to know how their bodyshapes changed since starting HIV drug treatment or how their bodyshapes will continue to change in the future.

While FRAMsuggests that lipoatrophy, and not lipohypertrophy, is the primaryconcern facing HIV-positive people, the cross-sectional study designdoesn’t really permit this conclusion. Without knowing when theHIV-positive people experienced lipohypertrophy – perhaps after HIVdrug treatment was started – it cannot be concluded that anti-HIVtreatment doesn’t cause a syndrome (lipodystrophy) that can result inlipohypertrophy and lipoatrophy (even if it is much more likely tocause lipoatrophy).

What’s more, FRAM did not compareHIV-positive people on anti-HIV treatment to HIV-positive people nottaking any anti-HIV medications. In turn, it can be very difficult tocome up with a real understanding of the body-shape changes caused byHIV or its medications, based on a study that includes onlyHIV-positive people on drug treatment to HIV-negative people not on HIVmedications.