Transcript Factors Associated with Regional Adipose Tissue in HIV+ Women

# N-159
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: [email protected]
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
Abstract
Objective: Both peripheral fat loss and central fat gain have been reported in women with HIV infection.
Results
Methods (continued)
Definition of Lipoatrophy and lipohypertrophy
•
We determined the fat changes that are specific to HIV infection in women and their associated factors.
Lipoatrophy: concordance between self-report of any decrease in body fat (mild, moderate, or
Table 2: Results of multivariate models# assessing association of HIV-related and non-HIVrelated factors with adipose tissue volume of leg SAT and VAT in HIV+ women*.
Figure 2: MRI (normalized by height2)
Leg**
Lipohypertrophy: concordance between self-report of any increase in body fat and exam of fat
excess
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
Lipoatrophy and lipohypertrophy were analyzed separately for peripheral and central sites:
individual depots were analyzed.
Results: Among HIV-infected women, those with central lipohypertrophy were less likely to have
•
6
4
Age (per decade)
– Central: neck, waist, abdominal fat, chest or upper back
2
•
VAT.
Arm Fat (L)
with reciprocally increased VAT or trunk fat.
Introduction
-10
(-23,7)
0.26
-32
(-47,-11)
<.0001
12
Physical Activity: (vs. 1st quartile)
2nd Quartile
3rd Quartile
4th Quartile
10
(-7,30)
2 (-23,33)
-20
(-38,3)
0.27
0.93
0.070
2
-12
-21
(-20,31)
(-44,37)
(-52,24)
0.79
0.57
0.32
10
Current HIV Viral Load (log 10)
-2
(-11,7)
0.58
-2
(-17,15)
0.84
8
Current CD4 100 (per doubling†)
-3
(-8,3)
0.41
12
(-1,26)
0.096
6
4
ARVs reaching statistical significance
for either depot (per year of use)
2
Stavudine
-9
(-12,-5)
<.0001
1
(-5,7)
0.78
0
NNRTI
-6
(-12,-1)
0.027
0
(-9,8)
0.88
-0.6
(-5,4)
0.83
7
(1,13)
0.033
p = 0.58
p < 0.001
HAART
p < 0.001
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
1
1. The association between concordance of self report of fat change and standardized
Race
examination of fat in peripheral depots and in central depots.
2. The association between regional adipose tissue volume in HIV-infected women with the
lipoatrophy, and control women
Height (cm)
Weight (kg)
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.
BMI (kg/m2)
Menopause€
HIV Risk Factor^
Methods
Reported HIV Duration (y)
HIV RNA (1000/mL)
Study Design: Multi-center cross sectional study
142
Median
39.0
42.0
Range
33.0-45.0
33.0-45.0
Caucasian
32%
49%
African-American
56%
51%
Hispanic
10%
0
Asian
1%
0
Native American
1%
0
Unknown
1%
0
Median
162.6
164.5
Range
142.5-185.6
149.9-192.0
Median
71.7
75.1
Range
32.7-140.2
42.9-117.7
Median
26.4
28.0
Range
13.0-47.7
17.5-47.8
Yes
6%
6%
No
80%
81%
Missing
14%
13%
Heterosexual contact
59%
IDU
26%
Other
15%
Median
8.5
Range
1.9-17.4
Median
0.8
Range
0.4-751.0
369
Range
Study Population: HIV-infected women enrolled from 16 infectious disease clinics across the US
(FRAM). Details regarding the recruitment, enrollment and study objectives and design of the FRAM
183
Median
CD4 (cells/uL)
between 2000 to 2002 for the Study of Fat Redistribution and Metabolic Change in HIV infection
Control
3-1600
p-value
<0.001
0.002
0.37
0.005
0.017
•
Whole body magnetic resonance imaging measured regional adipose tissue volume.
60
•
The clinical syndrome of peripheral lipoatrophy was not associated with central
4
lipohypertrophy or increased VAT.
•
2
p = 0.014
•
Use of stavudine and the ARV class, NNRTI were associated with less leg SAT, but
These results indicate that future research studies of fat distribution in HIV-infected
women should focus on measurements of fat, not clinical syndromes.
•
0
LA+ HIV
LA- HIV
Control
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
>0.99
not (2), highlights the need to study individual adipose tissue depots in women to
Figure 3. Results of multivariate models adjusting for other measures affecting
body fat in comparing adipose tissue depots in LA+, LA-, and controls (HeightAdjusted)
p-values are Group vs. Control
determine their etiology and associated metabolic findings.
References
n/a
Yes
No
HIV+ with clinical lipoatrophy
HIV+ without clinical lipoatrophy
120
p =0.035
100
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.
80
2. FRAM Study Investigators. Fat distribution in men with HIV infection. J Acquir Immune Defic
60
Syndr. 2005;40(2):121-131.
p =0.085
40
p =0.25
20
p =0.011
Acknowledgements
p =0.16
0
-20
-40
p =0.30
-60
-80
p =0.91
p <0.001
p <0.001
Lower
Trunk
Arms
Upper
Trunk
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
p <0.001
Legs
50
•
p = 0.008
not VAT. Rather, any form of HAART use was associated with more VAT.
n/a
OR = 0.39
CI = 0.20-0.75
p = 0.006
However, women without the clinical syndrome of lipoatrophy had less leg SAT
andmore VAT than controls.
1
0.16
n/a
90
70
6
0.5
n/a
100
80
These data support a syndrome of subcutaneous lipoatrophy in HIV-infected women.
1.5
Figure 1. Odds Ratios for Lipoatrophy and Lipohypertrophy in women
% with Peripheral Lipoatrophy
Measurements:
•
2
Results
(June 2001 to June 2002).
8
p = 0.37
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
p = 0.017
0
*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
Study have been described (1).
Upper Trunk Fat (L)
Age (y)
Therefore, we assessed:
clinical syndrome of peripheral lipoatrophy, those without the clinical syndrome of peripheral
HIV+*
VAT (L)
Data comparing fat changes in HIV-infected women with those of age matched control are limited.
Conclusions
p = 0.063
Table 1: Demographics of women between the ages of 33-45
n
are the boot strapped outcome for that ARV plus the HIV-related and non-HIV-related
0
% Difference in Adipose Tissue Volume vs. Controls
it is unknown whether these are independent or associated abnormalities.
#Values
p = 0.17
p = 0.001
Peripheral fat loss (lipoatrophy) and central fat gain have been reported in HIV-infected women but
0.089
0.78
0.95
Current Smoker vs non-smoker
2
Demographics
(-38,2)
(-32,56)
(-61,81)
0.031
3
values were compared by Mann-Whitney test.
Conclusions: Peripheral lipoatrophy occurs commonly in HIV-infected women, but is not associated
-21
6
1
(2,35)
p < 0.001
For comparisons of prevalence, p-values were calculated by Fisher’s exact test. Numerical
<.0001
0.40
0.29
p-value
18
acute changes in fat).
with less leg SAT, but was not associated with VAT. Use of HAART, however was associated with more
44 (23,72)
12 (-16,49)
-15 (-43,18)
95%CI^
0.13
14
malignancy within the same or previous month as the exam were excluded (in order to remove
more VAT and upper trunk SAT than controls. Use of the antiretroviral drug stavudine was associated
%
Effect
(-14,2)
p < 0.001
Analyses of HIV-associated factors including antiretroviral therapy in the HIV-infected women
p-value
-6
0
included 338 women between the ages of 19 and 70. Women with an opportunistic infection or
in the legs regardless of the presence of absence of lipoatrophy. However, those without lipoatrophy had
•
8
Lower Trunk Fat (L)
•
infected women without peripheral lipoatrophy. Compared to controls, HIV-infected women had less SAT
•
10
Analyses comparing HIV-infected women and controls in the same 33-45 year age range
%
95%CI^
Effect
Ethnicity (vs. Caucasian):
African-American
Hispanic
Other
– Peripheral: cheeks, face, buttocks, legs, and arms
included 183 HIV-infected women.
adipose tissue (SAT) in all peripheral and central sites and less visceral adipose tissue (VAT) than HIV-
•
12
Analysis:
lipohypertrophy. On MRI, HIV-infected women with clinical peripheral lipoatrophy had less subcutaneous
p = 0.005
p < 0.001
14
Leg Fat (L)
•
HIV Infection (FRAM) were compared. Lipoatrophy or lipohypertrophy was defined as concordance
peripheral lipoatrophy (OR=0.39, 95% C.I.: 0.20, 0.75, p=0.006) than those without central
p < 0.001
severe) and exam finding of fat wasting
Methods: HIV-infected and control women from the study of Fat Redistribution and Metabolic Change in
VAT**
VAT
DATA COORDINATING CENTER: Dale Williams • Heather McCreath • Cora E. Lewis •
Charles Katholi • George Howard • Tekeda Ferguson • Anthony Goudie
40
IMAGE READING CENTER: Steven Heymsfield • Jack Wang • Mark Punyanitya
30
SCIENTIFIC ADVISORY BOARD: Samuel Bozzette • Ben Cheng • Ann Collier • Steven Haffner •
John Phair
20
10
OFFICE OF PRINCIPAL INVESTIGATOR: Carl Grunfeld • Phyllis Tien • Peter Bacchetti •
Dennis Osmond • Michael Shlipak • Mae Pang • Heather Southwell
0
Central Lipohypertrophy
Central Lipoatrophy