FRAM Study Finds No Association between Fat Loss and Fat Accumulation in Men with HIV on Antiretroviral Therapy  

By Ronald Baker, PhD

Over the past decade, individuals with HIV infection have reported changes in body fat distribution, including peripheral lipoatrophy (fat loss) of face and limbs and lipohypertrophy (fat accumulation) in the form of dorsocervical fat pads, multiple lipomas, increased breast size, abdominal girth, and visceral adipose tissue (VAT). These two conditions have usually been referred to collectively as HIV-related lipodystrophy or fat redistribution syndrome.

HIV-related lipodystrophy has been associated with an increased risk of cardiovascular disease due to significant changes in the metabolic parameters of affected patients. In addition, these body fat changes have been severe enough to result in the stigmatization of many HIV positive individuals. This in turn has caused some patients either to stop taking their anti-HIV therapy or to postpone antiretroviral treatment, even when initiation of therapy is warranted.

Thus far, HIV-related lipodystrophy has been defined in studies based on a number of different perspectives: some by self-report, confirmed by a health care provider, on changes in either peripheral or central body sites. Some combine changes into one syndrome, and others report separately on lipoatrophy only, lipohypertrophy only, and combined syndromes. As a result of these differing perspectives, there has been considerable debate about an accurate definition of the syndrome(s).

In the recently published Fat Redistribution and Metabolic Changes in HIV Infection (FRAM) study [1], Carl Grunfeld et al evaluated self-reported changes in fat and physical examination findings by trained observers using specialized equipment. According to the authors, the study objectives were “to compare fat distribution as assessed by self-report, physical examination, and measurement by magnetic resonance imaging (MRI) in HIV-infected men with that in controls (HIV-uninfected men) and within HIV-infected men, to evaluate the interrelationships of fat distribution across peripheral and central regions, and their associations with antiretroviral (ARV) therapy.”

Results of the FRAM observational study appear in the October 1, 2005 issue of the Journal of Acquired Immune Deficiency Syndromes (JAIDS) and are summarized below:

	HIV-infected subjects were selected from patients seen in 16 HIV or infectious disease clinics or cohorts during 1999; Control subjects were recruited from 2 centers of the Coronary Artery Risk Development in Young Adults (CARDIA) study.
	Findings represent results of examinations of 425 HIV-infected men and 152 control men in the 33- to 45-year age range.
	HIV-positive men reported more fat loss than controls in all peripheral and most central depots.
	Peripheral lipoatrophy was more frequent in HIV-positive men than in controls (38.3% vs. 4.6%, P < 0.001), whereas central lipohypertrophy was less frequent (40.2% vs. 55.9%, P = 0.001).
	Among HIV-positive men, the presence of central lipohypertrophy was not positively associated with peripheral lipoatrophy.
	On MRI, HIV-positive men with clinical peripheral lipoatrophy had less subcutaneous adipose tissue (SAT) in peripheral and central sites and less visceral adipose tissue (VAT) than HIV-positive men without peripheral lipoatrophy.
	HIV-positive men both with and without lipoatrophy had less SAT than controls, with legs and lower trunk more affected than upper trunk.
	Use of the antiretroviral drugs stavudine [Zerit] or indinavir [Crixivan] was associated with less leg SAT but did not appear to be associated with more VAT;
	Nevirapine (Viramune) use was associated with less VAT.

In conclusion, the authors write, “Both peripheral and central subcutaneous lipoatrophy was found in HIV infection. Lipoatrophy in HIV-positive men is not associated with reciprocally increased VAT.” Further, they note that HIV positive men had less lipohypertrophy than controls, all of whom were HIV negative.

Discussion

The findings of the FRAM study show that HIV-infected men who had peripheral lipoatrophy had less adipose tissue in each peripheral and central depot than HIV-infected men without peripheral lipoatrophy.

Furthermore, HIV-infected men with or without peripheral lipoatrophy had less adipose tissue in both peripheral and central subcutaneous sites compared with control subjects, with lower body more affected than upper body using direct measurements of adipose tissue volume.

“Clinically, HIV-infected men were more likely to have peripheral lipoatrophy than controls, but they also had more central lipoatrophy and less central lipohypertrophy,” write the FRAM study authors.

The findings from self-report also show that loss of fat in peripheral and most central subcutaneous depots distinguished all HIV-infected men from controls. Furthermore, use of stavudine or indinavir was associated with less leg SAT, but the use of these drugs did not appear to be associated with more VAT.

“Thus,” say the authors, “our results argue against the proposals in earlier reports of a reciprocal syndrome of lipodystrophy in which peripheral fat loss is accompanied by central fat gain, including increased VAT.”

Furthermore, the authors conclude the data from this study suggest that future research studies of fat distribution in HIV-infected persons should focus on subcutaneous lipoatrophy and “direct measurements of regional adipose tissue (rather than surveys or subjective examination) should be used to determine cause and associated metabolic findings.”

In an editorial accompanying the FRAM study and also published in the October 1, 2005 issue of JAIDS [2], authors Milan Khara and Brian Conway state that the FRAM study demonstrates “there is no single morphologic syndrome in which an individual develops fat loss in the limbs and face and fat accumulation in the abdomen.”

“The key finding [of the FRAM study] was that a significantly greater proportion of HIV-infected men lost peripheral and central fat compared to control men, and that this was mild in half or more of the cases,” according to Khara and Conway.

In addition, they write, “There was no reciprocal increase in visceral fat. In fact, fat accumulation was more prevalent in the control group. Fat loss was associated with the use of stavudine and indinavir, but no other antiretroviral agents. There was no association of fat accumulation with any HAART components, except that nevirapine perhaps exerted a protective effect.”

It is hoped that the FRAM study findings will help lead researchers to the discovery of the causes of HIV-associated body fat changes and how best to prevent and treat them. Clearly this rigorous study contributes the methodology required to more accurately evaluate these changes. 

Sub Topics for Lipodystrophy-related Articles on HIVandHepatitis.com Lipodystrophy / Morphologic Changes (body shape changes) • Fat Loss (lipoatrophy) • Fat Accumulation (lipotrophy) • Buffalo Hump (BH) • Cardiovascular Disease • Cosmetic Procedures • Facial Implants • Growth Hormone • HIV Wasting • Hormone Therapies • Steroids • Visceral Adiposity Fat Redistribution • Fat Loss (lipoatrophy) • Fat Accumulation (lipotrophy) Metabolic Complications • Cardiovascular Disease • Cholesterol / Triglycerides • Diabetes • Dyslipidemias • Glucose Metabolism / Insulin Resistance • Gynecomastia • Hyperlactatemia • Hyperlipidemia • Infective Endocarditis • Myocardial Infarction (MI)

10/03/05

References

1. C Grunfeld and others. Fat Distribution in Men with HIV Infection. From the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). Journal of Acquired Immune Deficiency Syndromes 40(2):121-131. October 1, 2005.

2. M Khara and B Conway. Morphologic Changes in HIV-Infected Men: Sorting Fact from Fiction. Journal of Acquired Immune Deficiency Syndromes 40(2): 119-120. October 1, 2005.

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