Factors Associated with Regional Adipose Tissue in HIV Women

1
Factors Associated with Regional Adipose Tissue
in HIV Women
Contact Information Dr. Phyllis C. Tien,
M.D. Assistant Professor of Medicine UCSF VAMC 415
0 Clement St. San Francisco, CA 94121 USA Phone
415-221-4810 x 2577 Fax [phone] Email
ptien_at_medicine.ucsf.edu
N-159
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)

• 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 Fishers 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 (OR0.39, 95 C.I. 0.20,
0.75, p0.006) 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.
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.
200540(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 PIs 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 lt0.001
OR 0.39 CI 0.20-0.75 p 0.006
p lt0.001
p lt0.001
with Peripheral Lipoatrophy