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: ptien@medicine.ucsf.edu

# 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

0

10

20

30

40

50

60

70

80

90

100

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.