Factors Associated with Regional Adipose Tissue in HIV+ Women
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Transcript of Factors Associated with Regional Adipose Tissue in HIV+ Women
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:
• Analyses comparing 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.
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 infection in 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.
Factors Associated with Regional Adipose Tissue in HIV+ WomenPhyllis 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
Contact Information:Dr. Phyllis C. Tien, M.D.Assistant Professor of MedicineUCSFVAMC4150 Clement St. San Francisco, CA 94121 USAPhone: 415-221-4810 x 2577Fax: 415-379-5523Email: [email protected]
# N-159# N-159
Abstract
Introduction
• 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:
1. The association between concordance of self report of fat change and standardized
examination of fat in peripheral depots and in central depots.
2. 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
3. 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.
Methods (continued)
Table 1: Demographics of women between the ages of 33-45
HIV+* Control p-value
n 183 142
Age (y)Median 39.0 42.0
<0.001Range 33.0-45.0 33.0-45.0
Race
Caucasian 32% 49% 0.0020.37African-American 56% 51%
Hispanic 10% 0
Asian 1% 0
Native American 1% 0
Unknown 1% 0
Height (cm)Median 162.6 164.5
0.005Range 142.5-185.6 149.9-192.0
Weight (kg)Median 71.7 75.1
0.017Range 32.7-140.2 42.9-117.7
BMI (kg/m2)Median 26.4 28.0
0.16Range 13.0-47.7 17.5-47.8
Menopause€
Yes 6% 6%
No 80% 81% >0.99
Missing 14% 13%
HIV Risk Factor^
Heterosexual contact 59%
n/aIDU 26%
Other 15%
Reported HIV Duration (y)Median 8.5
n/aRange 1.9-17.4
HIV RNA (1000/mL)Median 0.8
n/aRange 0.4-751.0
CD4 (cells/uL)Median 369
n/aRange 3-1600
*Women with recent opportunistic infections were excluded€: Reported amenorrhea for more than 1 year or bilateral oopherectomy^: Data from 11 participants missingn/a = not available
Demographics
Results
Figure 2: MRI (normalized by height2)
0
2
4
6
8
10
12
14 p = 0.005p < 0.001
p < 0.001
ControlLA+ HIV LA- HIV
0
2
4
6
8
10
12
14p = 0.58
p < 0.001
p < 0.001
0
0.5
1
1.5
2
0
1
2
3
0
2
4
6
8
p = 0.008p = 0.014
p = 0.37
p = 0.017p = 0.001
p = 0.063
Leg Fat (L)
Lower Trunk Fat (L)
Arm Fat (L)
Upper Trunk Fat (L)
VAT (L)
p = 0.17
p < 0.001
p < 0.001
-80
-60
-40
-20
0
20
40
60
80
100
120
HIV+ with clinical lipoatrophyHIV+ without clinical lipoatrophy
% Difference in Adipose Tissue Volume vs. Controls
p <0.001 p <0.001
p <0.001 p =0.30 p =0.91
p =0.011p =0.25
p =0.085
p =0.16
p =0.035
LegsLowerTrunk Arms
Upper Trunk VAT
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
Leg** VAT**
%
Effect95%CI^ p-value
% Effect
95%CI^ p-value
Ethnicity (vs. Caucasian): African-American 44 (23,72) <.0001 -21 (-38,2) 0.089 Hispanic 12 (-16,49) 0.40 6 (-32,56) 0.78 Other -15 (-43,18) 0.29 1 (-61,81) 0.95
Age (per decade) -6 (-14,2) 0.13 18 (2,35) 0.031
Current Smoker vs non-smoker -10 (-23,7) 0.26 -32 (-47,-11) <.0001
Physical Activity: (vs. 1st quartile) 2nd Quartile 10 (-7,30) 0.27 2 (-20,31) 0.79 3rd Quartile 2 (-23,33) 0.93 -12 (-44,37) 0.57 4th Quartile -20 (-38,3) 0.070 -21 (-52,24) 0.32
Current HIV Viral Load (log 10) -2 (-11,7) 0.58 -2 (-17,15) 0.84
Current CD4 100 (per doubling†) -3 (-8,3) 0.41 12 (-1,26) 0.096
ARVs reaching statistical significance for either depot (per year of use)
Stavudine -9 (-12,-5) <.0001 1 (-5,7) 0.78
NNRTI -6 (-12,-1) 0.027 0 (-9,8) 0.88
HAART -0.6 (-5,4) 0.83 7 (1,13) 0.033#Values are the boot strapped outcome for that ARV plus the HIV-related and non-HIV-related factors. *Excludes participants with recent opportunistic infections.**Outcome is log (adipose tissue depot/ht2). Model controls for alcohol, crack/cocaine, heroin, and marijuana.^ 95% CI = 95% Confidence Interval† CD4 log transformed for analysis
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*.
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.
ReferencesMethods
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.
Results
Figure 1. Odds Ratios for Lipoatrophy and Lipohypertrophy in women
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Central Lipohypertrophy Central Lipoatrophy
Yes
No
OR = 0.39 CI = 0.20-0.75 p = 0.006
% with Peripheral Lipoatrophy
Acknowledgements
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
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.