Factors Associated with Regional Adipose Tissue in HIV+ Women

1. FRAM Leg Fat (L) Lower Trunk Upper Trunk Legs Arms VAT Lower Trunk Fat (L) p < 0.001 p = 0.005 p < 0.001 Arm Fat (L) p < 0.001 p = 0.58 p < 0.001 Upper Trunk Fat (L) p < 0.001 p < 0.001 p = 0.17 p = 0.063 VAT (L) p = 0.001 p = 0.017 p = 0.37 p = 0.014 p = 0.008 References LA+ HIV LA- HIV Control Acknowledgements Contact Information: Dr. Phyllis C. Tien, M.D. Assistant Professor of Medicine UCSF VAMC 4150 Clement St. San Francisco, CA 94121 USA Phone: 415-221-4810 x 2577 Fax: 415-379-5523 Email: ptien@medicine.ucsf.edu # N-159 Factors Associated with Regional Adipose Tissue in HIV+ Women Phyllis C. Tien1,2, Peter Bacchetti1, Joseph CoFrancesco3, Steven Heymsfield4, Cora Lewis5, and FRAM study 1University of California, San Francisco, CA, USA; 2San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA; 3Johns Hopkins University, Baltimore, MD, USA;4Merck, Rahway, NJ, USA; 5University of Alabama, Birmingham, AL, USA Results Abstract Methods(continued) Objective: Both peripheral fat loss and central fat gain have been reported in women with HIV infection. We determined the fat changes that are specific to HIV infectionin women and their associated factors. Methods: HIV-infected and control women from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) were compared. Lipoatrophy or lipohypertrophy was defined as concordance between participant report of fat change and clinical exam. Whole body MRI measured regional adipose tissue volumes. The relationship among different adipose tissue depots and factors associated with individual depots were analyzed. Results: Among HIV-infected women, those with central lipohypertrophy were less likely to have peripheral lipoatrophy (OR=0.39, 95% C.I.: 0.20, 0.75, p=0.006) than those without central lipohypertrophy. On MRI, HIV-infected women with clinical peripheral lipoatrophy had less subcutaneous adipose tissue (SAT) in all peripheral and central sites and less visceral adipose tissue (VAT) than HIV-infected women without peripheral lipoatrophy. Compared to controls, HIV-infected women had less SAT in the legs regardless of the presence of absence of lipoatrophy. However, those without lipoatrophy had more VAT and upper trunk SAT than controls. Use of the antiretroviral drug stavudine was associated with less leg SAT, but was not associated with VAT. Use of HAART, however was associated with more VAT. Conclusions: Peripheral lipoatrophy occurs commonly in HIV-infected women, but is not associated with reciprocally increased VAT or trunk fat. • Definition of Lipoatrophy and lipohypertrophy • Lipoatrophy: concordance between self-report of any decrease in body fat (mild, moderate, or severe) and exam finding of fat wasting • Lipohypertrophy: concordance between self-report of any increase in body fat and exam of fat excess • Lipoatrophy and lipohypertrophy were analyzed separately for peripheral and central sites: • Peripheral: cheeks, face, buttocks, legs, and arms • Central: neck, waist, abdominal fat, chest or upper back • Analysis: • Analysescomparing HIV-infected women and controls in the same 33-45 year age range included 183 HIV-infected women. • Analyses of HIV-associated factors including antiretroviral therapy in the HIV-infected women included 338 women between the ages of 19 and 70. Women with an opportunistic infection or malignancy within the same or previous month as the exam were excluded (in order to remove acute changes in fat). • For comparisons of prevalence, p-values were calculated by Fisher’s exact test. Numerical values were compared by Mann-Whitney test. Table 2: Results of multivariate models# assessing association of HIV-related and non-HIV-related factors with adipose tissue volume of leg SAT and VAT in HIV+ women*. Figure 2: MRI (normalized by height2) Introduction Demographics Conclusions • These data support a syndrome of subcutaneous lipoatrophy in HIV-infected women. • The clinical syndrome of peripheral lipoatrophy was not associated with central lipohypertrophy or increased VAT. • However, women without the clinical syndrome of lipoatrophy had less leg SAT andmore VAT than controls. • Use of stavudine and the ARV class, NNRTI were associated with less leg SAT, but not VAT. Rather, any form of HAART use was associated with more 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 (2), highlights the need to study individual adipose tissue depots in women to determine their etiology and associated metabolic findings. • Peripheral fat loss (lipoatrophy) and central fat gain have been reported in HIV-infected women but it is unknown whether these are independent or associated abnormalities. • Data comparing fat changes in HIV-infected women with those of age matched control are limited. • Therefore, we assessed: • The association between concordance of self report of fat change and standardized examination of fat in peripheral depots and in central depots. • The association between regional adipose tissue volume in HIV-infected women with the clinical syndrome of peripheral lipoatrophy, those without the clinical syndrome of peripheral lipoatrophy, and control women • Factors associated with the amount of subcutaneous adipose tissue (SAT) in the leg and visceral adipose tissue (VAT) – the two depots most commonly implicated in studies of fat distribution. Figure 3. Results of multivariate models adjusting for other measures affecting body fat in comparing adipose tissue depots in LA+, LA-, and controls (Height-Adjusted) p-values are Group vs. Control Methods • Study Design: Multi-center cross sectional study • Study Population: HIV-infected women enrolled from 16 infectious disease clinics across the US between 2000 to 2002 for the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM). Details regarding the recruitment, enrollment and study objectives and design of the FRAM Study have been described (1). • Control Population: Women from two sites (Birmingham, AL and Oakland Kaiser) of the population based Coronary Artery Risk Development in Young Adults (CARDIA) Study during the Year 15 exam (June 2001 to June 2002). • Measurements: • Whole body magnetic resonance imaging measured regional adipose tissue volume. 1. Tien P, Benson C, Zolopa A, Sidney S, Osmond D, Grunfeld C for the FRAM Study Investigators. The study of fat redistribution and metabolic change in HIV infection (FRAM): Methods, design, and sample characteristics. Am J Epidemiol. Accepted for publication. 2. FRAM Study Investigators. Fat distribution in men with HIV infection. J Acquir Immune Defic Syndr. 2005;40(2):121-131. p =0.035 *Women with recent opportunistic infections were excluded €: Reported amenorrhea for more than 1 year or bilateral oopherectomy ^: Data from 11 participants missing n/a = not available p =0.085 % Difference in Adipose Tissue Volume vs. Controls Results p =0.25 p =0.16 p =0.011 • Figure 1. Odds Ratios for Lipoatrophy and Lipohypertrophy in women SITE PI’s: Constance Benson • Joseph Cofranceso • Judith Currier • Michael Dube • Cynthia Gibert • Barbara Gripshover • Donald Kotler • Cora E. Lewis • W. Christopher Matthews • William Powderly • David Rimland • Michael Saag • Morris Schambelan • Abby Shevitz • Steve Sidney • Michael Simberkoff • Charles van der Horst • Andrew Zolopa SITE CO-Is: Juan Bandres • Adrian Dobs • Ellen Engelson • Lisa Gooze • Lisa Kosmiski • Daniel Lee • Matthew Leibowitz • Kathleen Mulligan • Barbara Smith • Christine Wanke • Kevin Yarasheski DATA COORDINATING CENTER: Dale Williams • Heather McCreath • Cora E. Lewis • Charles Katholi • George Howard • Tekeda Ferguson • Anthony Goudie IMAGE READING CENTER: Steven Heymsfield • Jack Wang • Mark Punyanitya SCIENTIFIC ADVISORY BOARD: Samuel Bozzette • Ben Cheng • Ann Collier • Steven Haffner • John Phair OFFICE OF PRINCIPAL INVESTIGATOR: Carl Grunfeld • Phyllis Tien • Peter Bacchetti • Dennis Osmond • Michael Shlipak • Mae Pang • Heather Southwell p =0.91 p =0.30 p <0.001 OR = 0.39 CI = 0.20-0.75 p = 0.006 p <0.001 p <0.001 % with Peripheral Lipoatrophy