Fat Distribution in Women With HIV Infection

Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM)

Disclosures

J Acquir Immune Defic Syndr. 2006;42(5):562-571. 

In This Article

Results

Participants

HIV-infected and control women between the ages of 33 and 45 years had similar proportions of African Americans ( Table 1 ). Both groups included significant numbers of whites. The control group was confined to African Americans and whites by design. Control women were on average slightly older. HIV-infected women had lower mean height and weight; however, BMI was similar between HIV-infected and control women. Few HIV-infected and control women reported being postmenopausal (n = 11 and n = 9, respectively). The primary mode of HIV transmission in the HIV-infected women was through heterosexual contact. HIV RNA levels and CD4 counts spanned the full spectrum of HIV infection.

Lipoatrophy and Lipohypertrophy by Self-Report, Examination, and Concordance

More HIV-infected women than controls reported loss of fat in the peripheral sites: cheeks, face, arms, buttocks, and legs (all P < 0.001) (Figure 1A). Likewise, for central sites, significantly higher proportions of HIV-infected women than controls reported decreases in waist size. Similar proportions of HIV-infected and control women reported loss of neck, chest, abdominal fat, and upper back fat, although the proportion for each was slightly higher among HIV-infected women.

Figure 1:

Prevalence of self-report of change in body fat over the previous 5 years. HIV-positive subjects and controls were surveyed for self-reported changes in fat in multiple anatomical areas and in waist size that occurred in the 5 years before the study. A, Decreased fat. B, Increased fat. HIV+ (solid bars); controls (open bars).

Many HIV-infected women reported gain in fat (Figure 1B). In all peripheral sites, the prevalence of fat gain was significantly lower in HIV-infected women than controls. For central sites, the proportion of HIV-infected women reporting increases in the chest, waist, and upper back were similar; the prevalence was not higher in HIV-infected women at any site. However, for central sites, fewer HIV-infected women reported increases in neck fat than control women.

Using the commonly accepted standard of self-report confirmed by physical examination to define fat changes, clinical lipoatrophy was more prevalent in all peripheral sites in HIV-infected women compared with controls (Figure 2A). At central sites, clinical lipoatrophy was uncommon in both HIV-infected and control women. Clinical lipohypertrophy was less prevalent in all peripheral sites and in the neck among HIV-infected women compared with controls. The prevalence of clinical lipohypertrophy was not higher in HIV-infected women than controls in any central site (Figure 2B).

Figure 2.

A, Prevalence of lipoatrophy by concordance. Subjects who reported loss of fat and had less fat than normal on examination were designated as having clinical lipoatrophy. B, Prevalence of lipohypertrophy by concordance. Subject who reported gain of fat and had more fat than normal on examination were designated as having clinical lipoatrophy. HIV+ (solid bars); controls (open bars).

We separately assessed the prevalence of clinical lipoatrophy and lipohypertrophy at any peripheral or central site. HIV-infected women were more likely to have peripheral lipoatrophy in at least 1 site compared with controls (28% vs. 4%; P < 0.001). The prevalence of clinical central lipoatrophy was low for both HIV and control (6% vs. 3%, respectively, P = 0.44) and the prevalence of central lipohypertrophy in at least 1 site was very high (62% vs. 63%, P = 0.91). Peripheral lipohypertrophy was less common among HIV-infected women compared with controls (35% vs. 62%, P < 0.001).

Magnetic Resonance Imaging Measurement of Regional Adipose Tissue Volumes

We compared adipose tissue volume measured by MRI among HIV-infected women with clinical peripheral lipoatrophy at 1 or more sites to those without clinical peripheral lipoatrophy and to controls (Figure 3). HIV-infected women with clinical peripheral lipoatrophy had less adipose tissue volume in the leg, lower trunk, arms, and upper trunk and less VAT than HIV-infected women without peripheral lipoatrophy. Compared with controls, HIV-infected women had less leg SAT regardless of the presence or absence of peripheral lipoatrophy. HIV-infected women with peripheral lipoatrophy also had less adipose tissue volume in the lower trunk and arms than controls. They appeared to have less upper trunk and VAT than controls, but these comparisons did not reach statistical significance. In contrast, HIV-infected women without peripheral lipoatrophy had more upper trunk SAT and VAT than controls, despite having less leg SAT. Lower trunk and arm SAT were similar.

Figure 3.

Adipose tissue volume by MRI. Comparison of controls, HIV-infected women with clinical peripheral lipoatrophy (LA+), and HIV-infected women without clinical peripheral lipoatrophy (LA-). Adipose tissue volume was divided by height squared, medians and CIs were calculated, and these then multiplied by 1.752 to correspond to a typical height. Values are median and CI. Leg is the region from the toes to the slice in which the leg separation is visible and no pubic bone occurs. Lower trunk is the region from the slice above the legs to the last slice where the liver area is greater than the lung. Upper trunk is the region from the first slice where the lung area is greater than the liver to the slice below the one where the arms are separated from torso. Arm is defined as the first slice where the arms are separated from torso to the end of the hands.

After multivariate analysis, HIV-infected women with peripheral lipoatrophy had significantly lower quantities of adipose tissue in leg, lower trunk, and arm than controls (Figure 4); the amount of VAT was similar. HIV-infected women without peripheral lipoatrophy also had significantly less adipose tissue in the legs than controls; the amount of VAT remained higher.

Figure 4.

Comparison of MRI findings in HIV subjects with and without clinical lipoatrophy versus controls. Results of multivariate models adjusting for non-HIV-related factors affecting adipose tissue volume in various fat depots. Percentage effects in HIV-infected groups versus controls are estimated in multivariate models of logarithmically transformed (adipose tissue per height squared by MRI), controlling for age (continuous), ethnicity, total physical activity score (categorical by quartile), smoking (current vs. past vs. never), current marijuana use (used 10+ days per month vs. 1 to 9 days vs. not used), current use of cocaine (crack or other forms, 10+ days per month vs. 1 to 9 vs. not used), heroin use (any in last 30 days vs. past use only vs. never used), speed use (any in last 30 days vs. past use only vs. never used), and reported adequacy of food eaten (enough vs. less). Hatched bars, HIV+ with lipoatrophy (LA+); open bars, HIV+ no lipoatrophy (LA-). P are versus controls.

Is Clinical Peripheral Lipoatrophy Associated With Central Lipohypertrophy?

We found evidence against any association linking peripheral lipoatrophy with central lipohypertrophy in women with HIV infection. The amount of adipose tissue measured by MRI in most sites was positively correlated with the amount of adipose tissue in most other sites regardless of whether the sites were peripheral or central, or whether correlations were examined among HIV-infected women with peripheral lipoatrophy, HIV-infected women without peripheral lipoatrophy, or controls (data not shown). For example, there was a positive correlation between leg SAT and lower trunk SAT in HIV-infected women with peripheral lipoatrophy (r = 0.48, P = 0.002) and HIV-infected women without peripheral lipoatrophy (r = 0.69, P < 0.001). Interesting exceptions were the lack of a correlation between leg SAT and VAT in either HIV-infected women with peripheral lipoatrophy (r = 0.09, P = 0.57) or those without peripheral lipoatrophy (r = 0.07, P = 0.48); women with low leg SAT had a wide range of VAT. Additionally, there was no substantial correlation between leg SAT and upper trunk SAT in HIV-infected women with peripheral lipoatrophy (r = 0.07, P = 0.68). However, there were no inverse correlations to suggest reciprocal changes of peripheral and central fat.

Likewise, loss of fat in individual peripheral sites by self-report was for the most part associated with loss of or less gain in fat at central sites (data not shown). An exception was that we found little correlation between self-report of fat change in the lower body (hips, buttocks, and legs) and fat change in the upper back. Again, there were no inverse correlations. When clinical examination data on fat were analyzed, less fat in individual peripheral sites was associated with less fat at all central sites studied.

As shown in Figure 5, among HIV-infected women, the presence of the clinical syndrome of central lipohypertrophy was strongly associated with a reduced likelihood of peripheral lipoatrophy (OR = 0.39; 95% CI, 0.20 to 0.75, P = 0.006). In contrast, every woman with central lipoatrophy also had peripheral lipoatrophy.

Figure 5.

Clinical peripheral lipoatrophy is not associated with central lipohypertrophy. The prevalence of peripheral lipoatrophy is presented on the y axis for those with (closed bars) or without (open bars) central lipohypertrophy (left side) or central lipoatrophy (right side).

Factors Associated With Leg SAT and VAT

Finally, we assessed ( Table 2 ) whether similar factors were associated with leg SAT (the most affected subcutaneous depot) and VAT (an important central depot that is associated with metabolic changes) among HIV-infected women using multivariate analysis. HIV-infected African-American women had more leg SAT than HIV-infected white women. This difference was similar to that seen in our control women (African-American women had 17% more leg SAT; 95% CI, 1.8 to 36.6, P = .027). Age was associated with more VAT and smoking with less VAT.

Among the ARVs evaluated, stavudine was significantly associated with less leg SAT. After adjustment for stavudine, no other individual ARV was associated. However, the ARV class NNRTI was associated with less leg SAT. We did not adjust for the NRTI class because stavudine is a NRTI, and no other NRTIs were found to be associated with leg SAT. HAART was found to be associated with more VAT. Individual ARV drugs not reaching significance for leg SAT and VAT are listed in the appendix.

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