In this multicenter study of HIV-infected women and controls, we made several important observations. First, HIV-infected women who had the clinical syndrome of peripheral lipoatrophy had less adipose tissue in each peripheral and each central depot than HIV-infected women without the syndrome of peripheral lipoatrophy. Second, HIV-infected women had less SAT in the legs than control women, regardless of the presence or absence of the clinical syndrome of lipoatrophy. Third, the clinical syndrome of peripheral lipoatrophy was not associated with the clinical syndrome of lipohypertrophy. However, HIV-infected women without the clinical syndrome of lipoatrophy had more VAT and upper trunk SAT than control women. Finally, among the individual ARVs and ARV classes evaluated, use of stavudine and the ARV class NNRTI were associated with less leg SAT, whereas the use of HAART was associated with more VAT.
Our results argue against previous descriptions of a "lipodystrophy syndrome" in which peripheral fat loss is accompanied by central fat gain, including increased VAT. Likely reasons for the observed differences in our study and previous reports[6,11,12,15,17,21,23,24,27,28,29,30,32] include our use of bidirectional questions to assess fat changes, our direct measurements of regional adipose tissue by MRI, and the comparison of HIV-infected and control women.
Our study found that peripheral lipoatrophy was not associated with central lipohypertrophy whether determined by self-report, examination, or concordance. Measurement by MRI also found that the clinical syndrome of peripheral lipoatrophy was not associated with increased VAT. However, our findings that upper trunk SAT and VAT was significantly higher in HIV-infected women without the clinical syndrome of peripheral lipoatrophy, who also had less leg SAT, may explain the previously proposed association of peripheral lipoatrophy with central lipohypertrophy.[11,12,13,15,17,18,20,21,23,24,27,28,29,30] Interestingly, we found that in HIV-infected men, VAT was similar between those with the clinical syndrome of peripheral lipoatrophy and those without the clinical syndrome of peripheral lipoatrophy. Although upper trunk SAT was higher in HIV-infected men without the clinical syndrome of peripheral lipoatrophy compared with those with the clinical syndrome, contrary to what we found in women, the amount of upper trunk SAT in both groups of HIV-infected men was less than in control men. The sex differences observed may be caused by the fact that women have more total body fat than men. Thus, although the clinical syndrome of peripheral lipoatrophy is not associated with the clinical syndrome of central lipohypertrophy, some women will have both a high amount of VAT and a low amount of leg SAT.
Our findings may also explain previous reports that HIV-infected women experience more central lipohypertrophy. First, only 28% of our HIV-infected women had the clinical syndrome of peripheral lipoatrophy by the accepted clinical approach of self report confirmed by examination compared with nearly 40% of FRAM HIV-infected men. Second, those without the clinical syndrome of lipoatrophy had more upper trunk SAT and VAT, yet direct measures of fat on MRI demonstrated less leg fat in all HIV-infected women compared with controls. Conversely, those with the clinical syndrome of lipoatrophy appear to represent those most severely affected with peripheral fat loss. Categorizing HIV-infected women by a clinical syndrome of peripheral lipoatrophy may underestimate the fat changes that occur.
Therefore, we used actual adipose tissue volumes in the leg and VAT to assess the associated factors. We found that the factors associated with leg SAT differed from those associated with VAT. Among the individual ARVs studied, the findings that stavudine was strongly associated with less leg SAT, but apparently not VAT, support the contention that HIV-related lipoatrophy is not linked to visceral obesity. The findings with stavudine confirm what we found in HIV-infected men from our cohort. However, the use of NNRTI as a class predicted less leg SAT in women (-6.0%; 95% CI, -11.5% to -0.8%, P = 0.026), but appeared to be more weakly associated with leg SAT in HIV-infected men from our cohort (-2.5%; 95% CI, -5.6% to 1.0%, P = 0.15). Similarly, indinavir use was associated with less leg SAT in men (-3.3%; 95% CI, -5.4% to -1.0%, P = 0.004), but may be less associated with reduced leg SAT in women (-2.5%; 95% CI, -7.5% to 3.6%, P = 0.50). These data could represent similar trends, but may suggest a sex-specific effect of NNRTI, which has not previously been reported. Most studies in women have not examined the association between the use of NNRTI and leg fat. These results should be examined in a randomized, prospective study of NNRTI use in a large cohort of women using direct measures of fat.
Our findings are different from another study in HIV-infected women, which reported an association between lamivudine and a clinical syndrome of both peripheral lipoatrophy and central lipohypertrophy. We found that the use of any form of HAART was associated with increased VAT; lamivudine is a common component of most HAART regimens. In the study of Gervasoni et al, most women with the clinical syndrome were also concurrently on stavudine. Because fat redistribution changes were defined as women with both peripheral lipoatrophy and central lipohypertrophy in that study, the independent effects of stavudine and lamivudine could not be determined. Combining findings that are inversely correlated with each other (peripheral lipoatrophy and central lipohypertrophy) could have led to misunderstandings.
Our findings are consistent with those of the WIHS, which found an increased incident risk of lipoatrophy in both peripheral and central sites in HIV-infected compared with uninfected women, but similar risk of central lipohypertrophy. WIHS also used bidirectional questions to ascertain body fat change. However, the clinical syndrome was defined using participant's self report of fat change confirmed by a change in anthropometric measurement in the same direction. Therefore, VAT could not be assessed and regional SAT depots were not directly measured. Interestingly, the BMI in HIV-infected women in the WIHS was significantly lower than their controls, whereas HIV-infected women in FRAM had similar BMI to controls. In a cross-sectional subset of WIHS women, stavudine was found to be associated with decreased leg fat on dual x-ray absorptiometry scans.
The primary limitation of our study was its cross-sectional design. We were not able to study changes in adipose tissue distribution over time. However, our study was performed approximately 5 years after the introduction of combination anti-retroviral therapy, which is adequate time to observe the evolution of the syndromes studied by others. Most women in our study were exposed to antiretroviral therapy, and so we were not able to address regional body composition in HIV-infected women not previously exposed to antiretroviral therapy. Our controls were not selected from women with similar risk behaviors as our HIV-infected women, as were the controls in the WIHS. Rather, we recruited women from a community-based study of healthy young whites and African Americans in the United States whose BMI measurements are similar to the larger, nationally representative NHANES III.
In summary, we find evidence for a syndrome of subcutaneous lipoatrophy in HIV-infected women. Peripheral lipoatrophy was not associated with central lipohypertrophy or increased VAT. Women who did not have the clinical syndrome of peripheral lipoatrophy had more VAT than controls. Thus, our findings are contrary to previous observations of a single syndrome of peripheral lipoatrophy and clinical lipohypertrophy. Likewise, antiretroviral drugs that were associated with lipoatrophy, as assessed by volume of leg fat, did not appear associated with central lipohypertrophy, as assessed by volume of VAT. Rather, any form of HAART was associated with increased VAT. These results indicate that future research studies of fat distribution in HIV-infected women should focus on measurements of fat, not clinical syndromes. Our finding that HIV-infected women without clinical peripheral lipoatrophy have more upper trunk SAT and VAT than control women, whereas HIV-infected men do not, highlights the need to study individual adipose tissue depots in women to determine their etiology and associated metabolic findings.
Supported by the National Institutes of Health grants RO1-DK57508, HL74814, HL 53359, and AI 027767, and National Institutes of Health GCRC grants M01-RR00036, RR00051, RR00052, RR00054, RR00083, RR0636, and RR00865.
Phyllis C. Tien, MD, University of California, San Francisco, Veterans Affairs Medical Center, Infectious Disease Section 111W, 4150 Clement Street, San Francisco, CA 94121 (e-mail: email@example.com ).
J Acquir Immune Defic Syndr. 2006;42(5):562-571. © 2006 Lippincott Williams & Wilkins
The funding agency reviewed the study design but played no role in collection, management, analysis, or interpretation of the data or in the preparation of the manuscript. The National Institutes of Health personnel participated as members of the Coronary Artery Risk Development in Young Adults Publications Committee that reviewed and approved the manuscript.
Cite this: Fat Distribution in Women With HIV Infection - Medscape - Aug 01, 2006.