Significant associations between BMI and SAT, VAT, trunk fat, and total extremity fat were observed for HIV-infected and non-HIV-infected men (Fig. 1). Regression lines were parallel, and intercepts differed significantly in the comparison of the relation of SAT to BMI between the HIV-infected and non-HIV-infected groups. SAT was decreased by approximately 21 cm2 for a given BMI among the male HIV-infected subjects compared with non-HIV-infected subjects. In contrast, the slopes of the regression lines relating VAT or VAT/SAT to BMI differed significantly between the HIV-infected and non-HIV-infected groups.
Trunk fat was not increased for a given BMI in male HIV-infected versus non-HIV-infected subjects, but total extremity fat was lower by 1.1 kg across the range of BMI for male HIV-infected compared with non-HIV-infected subjects. Trunk/total extremity fat was increased for male HIV-infected versus non-HIV-infected subjects, but differences between HIV-infected and non-HIV-infected men decreased with increasing BMI. Trunk/total extremity fat did not increase with BMI among HIV-infected men but did increase with BMI among non-HIV-infected men (see Fig. 1).
Analyses of HIV-infected patients and controls without metabolic syndrome as defined by NCEP/ATP III guidelines revealed similar results to the primary findings among all the subjects (Fig. 2).
Seventy-two (43%) male HIV-infected subjects and 22 (32%) male control subjects were of normal weight, 70 (42%) male HIV-infected subjects and 27 (40%) male control subjects were overweight, and 26 (15%) male HIV-infected subjects and 19 (28%) male control subjects were obese using WHO criteria. VAT was significantly higher and SAT was significantly lower among HIV-infected compared with non-HIV-infected men in the normal weight and overweight categories but not in the obese category. The difference in VAT was most significant among those in the normal weight category (104.6 ± 58.5 cm2 vs. 57.3 ± 25.5 cm2; P = 0.0004 [HIV-infected vs. controls]), whereas the difference in SAT was most significant among those in the overweight category (178.5 ± 85.6 cm2 vs. 242.2 ± 60.0 cm2; P = 0.0006 [HIV-infected vs. controls]) (Fig. 3).
Consistent with linear regression modeling, trunk fat was not increased among HIV-infected versus non-HIV-infected men for any BMI category, whereas total extremity fat was decreased in the normal and overweight categories and tended to be decreased in the obese category. Trunk/total extremity fat was therefore significantly increased in the normal and overweight categories, driven primarily by lower total extremity fat values (Table 3A).
NRTI and NNRTI use did not differ among HIV-infected men within the 3 BMI categories. The percentage of HIV-infected men receiving PIs was lower in the obese category compared with the other 2 BMI categories (48.0% PI use in obese vs. 74.2% in normal and 78.8% in overweight; P = 0.01). VAT (151.4 ± 70.4 cm2 vs. 136.2 ± 72.0 cm2; P = 0.23 [no PI vs. PI use]) and SAT (188.4 ± 119.0 cm2 vs. 162.1 ± 108.6 cm2; P = 0.19 [no PI vs. PI use]) did not differ by PI use, nor did PI use influence VAT or SAT in regression modeling accounting for BMI category (P = 0.74 for VAT and P = 0.52 for SAT).
Significant associations were observed between BMI and SAT, VAT, trunk fat, and total extremity fat for HIV-infected and non-HIV-infected women (see Fig. 3). The relation of SAT to BMI was not significantly different between the HIV-infected and non-HIV-infected women. In contrast, the relations of VAT and VAT/SAT to BMI differed significantly between HIV-infected and non-HIV-infected women.
Regression lines were parallel, and intercepts differed significantly in the comparisons of trunk fat and total extremity fat to BMI between HIV-infected and non-HIV-infected women. For a given BMI, female HIV-infected subjects demonstrated increased trunk fat and decreased total extremity fat by differences of approximately 0.67 kg and 0.85 kg, respectively, compared with non-HIV-infected subjects. Trunk/total extremity fat did not increase with BMI among HIV-infected women in contrast to non-HIV-infected women (Fig. 4).
Analyses of HIV-infected patients and controls without metabolic syndrome as defined by NCEP/ATP III guidelines revealed similar results to the primary findings among all the subjects (Fig. 5).
Forty-six (33%) female HIV-infected subjects and 14 (36%) female control subjects were of normal weight, 53 (39%) female HIV-infected subjects and 13 (33%) female control subjects were overweight, and 39 (28%) female HIV-infected subjects and 12 (31%) female control subjects were obese using WHO criteria. VAT was significantly higher among HIV-infected compared with non-HIV-infected women in the normal weight and overweight categories but not in the obese category. The difference in VAT was most significant among those in the normal weight category (76.6 ± 48.9 cm2 vs. 36.7 ± 13.9 cm2; P = 0.004 [HIV-infected vs. controls]). In contrast, SAT was significantly higher among HIV-infected compared with non-HIV-infected women in the obese category (472.4 cm2 ± 113.9 vs. 400.1 ± 83.7 cm2; P = 0.048) (Fig. 6).
Trunk fat values were significantly higher in the HIV-infected women in the normal and overweight categories and tended to be higher in the obese category (see Table 3B). HIV-infected women demonstrated higher trunk fat/total extremity fat across all BMI categories.
Protease inhibitor (PI), nucleoside reverse transcriptase inhibitor (NRTI), and nonnucleoside reverse transcriptase inhibitor (NNRTI) use was similar among the HIV-infected women across the 3 BMI categories. VAT (118.1 ± 64.0 cm2 vs. 120.4 ± 66.9 cm2; P = 0.85 [no PI vs. PI use]) and SAT (300.4 ± 181.0 cm2 vs. 278.2 ± 139.1 cm2; P = 0.46 [no PI vs. PI use]) did not differ by PI use, nor did PI use influence VAT or SAT in regression modeling accounting for BMI category (P = 0.76 for VAT and P = 0.53 for SAT).
Although BMI has been used as a simple anthropometric predictor of type 2 diabetes, hypertension, dyslipidemia, and cardiovascular disease among non-HIV-infected individuals,34-37 few studies have evaluated body composition between HIV-infected and non-HIV-infected control subjects in relation to BMI. We therefore examined the relation between body composition and BMI for HIV-infected compared with non-HIV-infected subjects in linear regression modeling and used the WHO BMI criteria to determine fat distribution differences between HIV-infected and non-HIV-infected subjects within these anthropometric subgroups.17
Our study demonstrated the significant presence of peripheral lipoatrophy among HIV-infected compared with non-HIV-infected subjects, supporting the findings of the FRAM study and others.14-16,38 For any given BMI, HIV-infected male subjects demonstrated 1.1 kg less total extremity fat and HIV-infected female subjects demonstrated 0.85 kg less total extremity fat compared with their respective non-HIV-infected controls. To our knowledge, this is the first study to quantify the degree of fat loss in relation to BMI between HIV-infected and non-HIV-infected subjects stratified by gender. We have also shown that in addition to the presence of peripheral lipoatrophy among HIV-infected individuals, significant alterations in VAT, SAT, and truncal fat occur in the context of BMI within gender categories.
Among HIV-infected men, abdominal SAT was significantly lower compared with non-HIV-infected men by an average difference of 21 cm2, and the largest differences were seen among normal and overweight HIV-infected men compared with control subjects. In contrast, VAT was increased among HIV-infected men in the normal and overweight categories compared with control subjects. Simultaneous increases in VAT and decreases in SAT may help to explain the observation that trunk fat per se was not different between HIV-infected and non-HIV-infected men.
Among HIV-infected women, trunk fat was increased by approximately 0.67 kg compared with non-HIV-infected female control subjects. Similar to the observation in men, VAT was increased most among HIV-infected women in the normal and overweight categories relative to controls. In contrast to the findings among men, SAT was not different between normal weight and overweight subjects (HIV-infected subject vs. control); thus, the increased trunk fat in these categories was primarily attributable to increased VAT, whereas in the obese category, the increased trunk fat was attributable to increased SAT. Women have more total body fat than men and tend to preserve gluteal and femoral fat stores,39 which may help to explain observed differences between HIV-infected men and women in this and other studies.14,15
HIV-infected and control subjects (male and female) also demonstrated increasing VAT and SAT deposition with increasing BMI, supporting the results of other studies of non-HIV-infected individuals.40 Thus, although absolutes levels of VAT increase with increasing BMI, relative differences compared with control subjects are greatest for normal and overweight HIV-infected patients (male and female). These findings suggest that (1) obesity alone does not predict increased visceral adiposity among HIV-infected subjects relative to non-HIV-infected subjects and (2) HIV-infected subjects at relatively lower BMIs may have increased risk of metabolic complications, given the degree of visceral adiposity observed.
In the FRAM study,14,15 patients were categorized based on the presence of lipoatrophy. Among men, a trend toward more VAT and significantly more trunk fat was demonstrated in HIV-infected patients without lipoatrophy compared with those with lipoatrophy. In contrast, VAT was lower compared with non-HIV-infected controls in those with lipoatrophy. Among women, more VAT and trunk fat were seen among HIV-infected subjects without lipoatrophy compared with HIV-infected patients with lipoatrophy and with non-HIV-infected controls. Subjects were not compared in relation to BMI or within BMI categories in the FRAM study; rather, adipose tissue volume for each subject was divided by height squared and then multiplied by 1.752 to correspond to a typical height. In contrast, HIV-infected patients and controls were compared in relation to BMI and within BMI categories in our study, suggesting relatively more VAT deposition among HIV-infected patients compared with controls at lower BMIs, particularly in the normal and overweight BMI categories, for both genders. Thus, our data extend those of the FRAM study, demonstrating relative differences in fat accumulation and fat loss by BMI category between genders.
This study has a number of limitations. We assessed body composition among HIV-infected individuals with a high proportion of metabolic abnormalities. Our results therefore cannot be generalized to all HIV-infected individuals or to HIV-infected individuals with wasting. Similar results were obtained when body composition parameters were compared between HIV-infected and non-HIV-infected patients using an identical criterion of absence of NCEP/ATP III-defined metabolic syndrome, however. These data suggest that the changes in body composition among the HIV-infected patients relative to controls in this study were not significantly biased by selection of patients with a high proportion of metabolic abnormalities. We did not follow patients longitudinally to determine changes in adipose distribution over time. Finally, we were unable to analyze the respective contributions from deep and superficial subcutaneous compartments, which may help to define the specific adipose changes that are occurring among HIV-infected individuals. Despite these limitations, these data provide new information on the relation of body composition to BMI among HIV-infected patients.
In conclusion, we have demonstrated differences in central and peripheral fat depots in relation to BMI and by WHO BMI category in the comparisons of male and female HIV-infected versus control subjects. Loss of extremity fat was the most consistent finding, but increased VAT was also observed relative to control subjects among HIV-infected men and women. The differences in VAT were most obvious among normal and overweight subjects. Gender differences in abdominal SAT accumulation were observed, with preservation of SAT among HIV-infected women relative to control subjects.
The authors are grateful to the nursing staff of the MGH and MIT General Clinical Research Centers for their dedicated patient care and to Matt Kron for his help with the analysis.
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Keywords:© 2008 Lippincott Williams & Wilkins, Inc.
body composition; body mass index; HIV; visceral adiposity