Washington D.C., USA, 22-27 July 2012www.aids2012.org
Aging, HIV and Women
Kathryn Anastos MDProfessor of Medicine and Epidemiology
Albert Einstein College of Medicine
Washington D.C., USA, 22-27 July 2012www.aids2012.org
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17% 19% 21% 22%25% 27% 27% 29%
33% 35% 37% 39% 41%44% 45% 47% 50%
Projected Proportion of those Living With HIV in United States 50+ Years*
2001-2017
*Data from 2008, onward projected based on 2001-2007 trends (calculated by Justice, AC), 2001-2007 data from CDC Surveillance Reports 2007
Projected
Washington D.C., USA, 22-27 July 2012www.aids2012.org
84.4% of women living with HIV are AfricanPhoto Jonathan Wallen
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Photo Jonathan Wallen
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Our brief foray into aging in HIV+ women
• Menopause as an inflammatory state• HIV as an inflammatory state• 3 clinical conditions
– Cardiovascular disease– Bone disease– Neurocognition
• Research agenda
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Women’s Interagency HIV Study (WIHS) Sites
Bronx, NYChicago, IL Brooklyn, NY
Baltimore, MD(Data Center)Washington, D.C.
Los Angeles, CA
San Francisco, CA
Washington D.C., USA, 22-27 July 2012www.aids2012.org
WIHS Cohort3818
Seroprevalent: 2843 (74%) Seronegative: 975 (26%)
AIDS AIDS9 (39%)1352 (64%)
AIDS baseline719 (25%)
AIDS-free baseline2124 (75%)
Seroconverter23 (2%)
Seronegative952 (98%)
DeadDead423 (59%)
Dead Dead64 (7%)
Dead
14 (61%)
Deadb
AIDS-free AIDS-free
323 (42%) 212 (16%)
772 (36%)
5 (56%) 3 (21%)
Washington D.C., USA, 22-27 July 2012www.aids2012.org
94/95 Cohort 01/02 CohortHIV+ HIV- HIV+ HIV-
Median age 36 34 33 29Race/ethnicity African-American 56% 54% 60% 61% Latina 23% 28% 32% 28%Exposure Category Intravenous drug use 34% 28% 10% 13% Heterosexual sex 42% 26% 41% 24% Transfusion risk 4% 3% --b --b
No identified risk 20% 43% 48% 63%
8
Baseline Characteristics(Barkan, Melnick, . . . , Feldman, Epidemiology 1998; 9:117-125)a
a 01/02 cohort data added. b Transfusion risk not assessed in 01/02 cohort.
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Cytokine changes in menopause and HIV infection
• Menopause causes increased levels of pro-inflammatory cytokines: IL-6, IL-1, TNF alpha
• Untreated HIV infection causes high levels of circulating pro-inflammatory cytokines: IL-6, IL-1, TNF alpha
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Cardiovascular Disease
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Bone Disease
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Bone strength: a major determinant of fracture risk
Bone Strength
Bone QualityBone Density
Rate of Remodeling MicroarchitectureBone size and shapeMineralizationMatrix quality
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Evolution of bone mass: declines with age and sex hormones
Orwoll ES et al. Endocr Rev. 1995;16(1):87-116.
BM
D
Women
Men
Peak
Men: 0.5-1.0% reduction in BMD/yr
Age (Yrs)
0
0.2
0.4
0.6
0.8
1.0
1.2
0 10 20 30 40 50 60 70 80
Women: 1.0-2.0% reduction in BMD/yr
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Hypothetical evolution of bone mass with HIV infection
Adapted from Orwoll ES et al. Endocr Rev. 1995;16(1):87-116.
BM
D
Women
Men
Peak
HIV infection
Age (Yrs)
0
0.2
0.4
0.6
0.8
1.0
1.2
0 10 20 30 40 50 60 70 80
ART initiation
HIV+ Men
HIV+ Women
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Tibial cortical thickness 12% lower in HIV+ postmenopausal women
HIV+ Age=61
HIV- Age=61
Yin, IOF-ECCEO 2012
Ct vBMD (m
g HA/cm
3)
Ct thick
ness (μm)
Tb vBMD (m
g HA/cm
3)0tan28a566028
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HIV+HIV-
P<0.01
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Higher prevalence of fracture in HIV+
Triant, JCEM, 2008
Female Male
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Higher incidence of fracture in HIV+
WIHS HOPS VAC Denmark 0tan28a566028
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HIV+HIV-*
*
frac
ture
per
100
0 pe
rson
-yea
rs
Increased fracture in multivariate models: Age, weight, caucasian, smoking, ETOH, glucocorticoids, PPI, HCV
Yin, 2010; Young, 2011; Womack, 2011; Hansen, 2011
*
HIV+ 1728 5826 40115 5306HIV- 663 NA 79203 26530
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Host
ART Virus
Multifactorial etiology of bone loss in HIVSmoking/alcoholGlucocorticoidsHCV infection
Weight lossHypogonadismDecreased activity
LipodystrophyCKDVitamin D deficiency
Direct effect of viral proteins on bone cellsImmune activation
Direct effect on bone cellsInadequate mineralizationImmune reconstitution
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Neurocognitive Function and Menopause in HIV-infected women
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Understanding menopausal symptoms in HIV-infected women:
Cross-sectional findings from the WIHS
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1. Are HIV-infected women at increased risk for menopausal symptoms?
2. Does menopausal stage influence depressive symptoms in HIV-infected women?
3. Do menopausal symptoms influence cognitive function in HIV-infected women?
Specific Questions Addressed
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As expected, menopausal symptoms are more common in peri- and postmenopausal stages compared to premenopausal stage
Note: Referent reproductive stage was premenopausal. Adjusted for relevant sociodemographic, clinical and behavioral variables. 55% premenopausal,15% early perimenopausal, 5% late perimenopausal, 25% postmenopausal.
Symptom Domains
Early
Per
i
Late
Per
i
Post
Early
Per
i La
te P
eri
Post
Early
Per
i
Late
Per
i
Post
Early
Per
i
Late
Per
i
Post
Early
Per
i
Late
Per
i
Post
* *
**
**
1
4
7
10
Decreased Likelihood
Increased Likelihood
Mood Sleep Vasomotor Somatic Vaginal
Odd
s Rati
o
*P<0.05.
* *
Reproductive Stage
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The only menopausal symptom that was increased in HIV+ women compared to HIV-women was night sweats
• After adjusting for relevant sociodemographic, clinical, and behavioral variables:
**
*P<0.05.
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Results: Depressive Symptoms on CES-D Are Increased During Early Perimenopause
Decreased Likelihood
Increased Likelihood
Predictors
Note: HIV-infected women (N = 835) and at-risk HIV-uninfected women (N =335). Referent for early peri, late peri, and post was premenopausal. “Recent Use” refers to in the past 6 months. CD4 count was an additional predictor in HIV-infected women.
0
1
2
3
4
5O
dds R
atio
HIV+
Early
Per
i
Late
Per
i
Post
Une
mpl
oyed
Inco
me
12
,000
/yr
2
Sexu
alPa
rtne
rs
Curr
ent
Smok
ing
Rece
nt U
se o
fAn
tidep
ress
ant
Med
s
**
** *
*
Odds Ratio and 95% CI
*P <0.05.
Maki et al. (in press) Menopause
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Results: Depressive Symptoms on CES-D Are Increased During Early Perimenopause in HIV-infected women who are ART naïve
Decreased Likelihood
Increased Likelihood
Odd
s Rati
o
Odds Ratio and 95% CINote. *p< .01. HAART use refers to use in the previous six months. Model is adjusted for age, race/ethnicity, site, education, employment, past history of probable depression, former menopausal hormone therapy use, persistent vasomotor symptoms, self-reported former and recent antidepressant medication use, and CD4 count. Maki et al. (in press) Menopause
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Menopause-related anxiety symptoms impact verbal learning more in HIV+ vs. HIV- women
*
Note:*p=0.001. Adjusted for relevant sociodemographic, clinical, and behavioral variables.
Worse Learning
Better Learning
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Summary
• Midlife women with HIV were at risk for (compared to premenopausal women) but not differentially at risk for (compared to HIV- women):– Any menopausal symptom except night sweats– Depression during the perimenopausal period
• Worsening of mood during the menopausal transition may lower ability of HIV+ women to learn and remember verbal material (i.e., word lists)
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AMH: AntiMüllerian Hormone• Dimeric glycoprotein growth factor that in
females is produced by ovarian granulosa cells of primary follicles
• Indicative of total ovarian primary follicle pool, expression decreases in late follicular maturation, so levels are not a factor of follicular development, and thus can be measured when ovulation is not occurring
ALL Durlinger, et al. Reproduction. 124:601, 2002.
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Summary
• Studies of men do not inform us adequately about disease in women
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Summary and Research Needs• Are there sex differences in HIV-induced inflammation:
We need to define the inflammatory state in HIV+ women
• Must conduct studies – in African women—carry the greatest burden of HIV
infection—– and in countries where the metabolic and CV
disease burden is high• Must conduct clinical and translational studies across
the full age range of women, with focus on menopause when studying aging
Washington D.C., USA, 22-27 July 2012www.aids2012.org42
WIHS Sites and Principal Investigators
• Consortia:– Bronx, New York (K. Anastos)– Brooklyn, New York (H. Minkoff)– Chicago, Illinois (M. Cohen)– Los Angeles, California (A. Levine)– Northern California (R. Greenblatt)– Washington, D.C. (M. Young)
• Data Coordinating Center (WDMAC):– Johns Hopkins University, Baltimore, Maryland (S.
Gange)
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WIHS Sponsoring Institutions (Program Officers)
• National Institute of Allergy and Infectious Diseases (J. Roe)– National Cancer Institute (G. Dominguez)– Eunice Kennedy Shriver National Institute of
Child Health and Human Development (H. Watts)
– National Institute on Drug Abuse (K. Davenny)
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Thanks• WIHS collaborators
– Robert Kaplan– Pauline Maki– Michael Yin– Ruth Greenblatt
• WIHS participants
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Photo Jonathan Wallen
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