For several years, beginning with the widespread use of anti-HIV drug combination therapy, the different types of body-shape changes (lipohypertrophy and lipoatrophy) have been reported by numerous HIV-positive people and their healthcare providers. In turn, they were both unofficially lumped together as being a part of the same syndrome, likely caused by anti-HIV drug treatment. However, it's still not clear if these two different types of body-shape changes are really related. Some HIV-positive people don't have any signs of lipoatrophy or lipohypertrophy, some experience one or the other, whereas others experience both. Because different HIV-positive people seem to experience different problems, it has been difficult to establish an official "case definition" of lipodystrophy. And for researchers to really understand the cause(s), prevention, and treatment of lipodystrophy, an official case definition needs to be determined.
To better understand how these problems are connected, and to help come up with an official case definition of lipodystrophy, researchers have been conducting important studies involving HIV-positive people with these symptoms. The first study to come up with a case definition was headed by Dr. Andrew Carr of St. Vincent's Hospital in Sydney, Australia. Results from the Lipodystrophy Case Definition (LDCD) study, an international effort involving 32 clinical research centers and 1,081 HIV-positive patients worldwide, were reported in 2003. In short, the study indicated that both lipohypertrophy and lipoatrophy are features of lipodystrophy. The study also suggested that the two features are linked to each other—where there is an increase in visceral fat there will most likely be a decrease in subcutaneous fat (and vice versa).
The connection between lipoatrophy and lipohypertrophy has been questioned with the publication of data from the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) study. The study was headed by Dr. Carl Grunfeld of the University of California, San Francisco. Unlike the LDCD study, which only enrolled HIV-positive people, the FRAM study enrolled both HIV-positive and HIV-negative volunteers. It has enrolled 825 HIV-positive men, 350 HIV-positive women, and 338 HIV-negative people.
Results focusing on men enrolled in FRAM were published in October 2005. Results focusing on women enrolled in FRAM were published in August 2006.
The study demonstrated that lipoatrophy was much more common in the HIV-positive volunteers than in the HIV-negative study participants. Approximately 38% of the HIV-positive men had "clinical" lipoatrophy of at least one part of the body—fat loss that was reported by the study participants and confirmed by the researchers during a physical examination—compared to approximately 4% of the HIV-negative men. Clinical lipoatrophy was also documented in 28% of the HIV-positive women compared to 4% of the HIV-negative women.
The study also demonstrated that HIV-positive people do experience lipohypertrophy. However, this buildup of fat—which was confirmed using MRI scans—was actually more common in the HIV-negative men than in the HIV-positive men. Approximately 40% of the HIV-positive men had lipohypertrophy, compared to approximately 56% of the HIV-negative men. Among women, reported lipohypertrophy was similar in both groups. Approximately 62% of the HIV-positive women had lipohypertrophy of at least one part of the body, compared to 63% of the HIV-negative women.
These study results indicate that lipoatrophy is a unique complication caused by HIV and/or HIV medications, whereas lipohypertrophy is not, given that visceral fat increases were similar among the HIV-positive and HIV-negative women and even more common in the HIV-negative men. The study also suggested that lipoatrophy and lipohypertrophy are not linked—patients who had increased visceral fat were more likely to have increased (not decreased) subcutaneous fat. In other words, FRAM suggests that visceral fat and subcutaneous fat either increase together or decrease together; one doesn't go up while the other goes down.
The FRAM results—especially the way they were reported in the mainstream media—have upset a lot of people. A common misperception of the FRAM study is that lipohypertrophy is not a problem for HIV-positive men or women. However, the study does not say this. It concludes that abnormal fat increases can and do occur in HIV-positive people, but not necessarily to a greater extent than HIV-negative men. Nor does the FRAM study suggest that these fat increases are "healthy," given that they are also seen in HIV-negative people. Numerous experts, including those associated with the FRAM study, continue to stress that enlarged visceral fat deposits are not healthy; they can cause serious problems for both HIV-positive and HIV-negative people.
Some experts have suggested that the reason why visceral fat increases look so much worse in HIV-positive people compared to HIV-negative people is because of the profound loss of fat in the arms, legs, and face caused by lipoatrophy, making the rest of the body look much bigger. However, without studies to confirm this, these comments must be considered purely speculative.
It is important to recognize that FRAM is not a perfect study. For starters, it is a cross-sectional study. This means that the study relied on a one-time "snapshot" of all patients enrolled. Because it didn't follow the study volunteers over time, it's impossible to know how their body shapes changed since starting HIV drug treatment or how their body shapes will continue to change in the future. While FRAM suggests that lipoatrophy, and not lipohypertrophy, should be included in the case definition of lipodystrophy, FRAM's cross-sectional study design doesn't really permit this conclusion. Without knowing when the HIV-positive people experienced lipohypertrophy—perhaps after anti-HIV drug treatment was started—it cannot be concluded that anti-HIV treatment doesn't cause a syndrome (lipodystrophy) that can result in lipohypertrophy and lipoatrophy (even if it is much more likely to cause lipoatrophy). What's more, FRAM did not compare HIV-positive people on anti-HIV treatment to HIV-positive people not taking any anti-HIV medications. In turn, it can be very difficult to come up with a case definition based on a study that includes only HIV-positive people on drug treatment to HIV-negative people. It should also be noted that, at least among the men participating in FRAM, the HIV-negative volunteers were more likely to be overweight than the HIV-positive volunteers. This may have skewed the results of the study.
Based on the results of FRAM (and other studies that reported similar findings), it is clear that we are still a ways off from an official case definition for lipodystrophy. Is it lipohypertrophy and lipoatrophy, or is it just lipoatrophy? How are high levels of fats and sugar in the blood related to body-shape changes? Hopefully additional studies will settle this once and for all.
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