aging, hiv and women

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


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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


84.4% of women living with HIV are AfricanPhoto Jonathan Wallen


Photo Jonathan Wallen


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


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


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%)


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.


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


Cardiovascular Disease


Bone Disease


Bone strength: a major determinant of fracture risk

Bone Strength

Bone QualityBone Density

Rate of Remodeling MicroarchitectureBone size and shapeMineralizationMatrix quality


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


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


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

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HIV+HIV-

P<0.01


Higher prevalence of fracture in HIV+

Triant, JCEM, 2008

Female Male


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


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


Neurocognitive Function and Menopause in HIV-infected women


Understanding menopausal symptoms in HIV-infected women:

Cross-sectional findings from the WIHS


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


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


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.


Results: Depressive Symptoms on CES-D Are Increased During Early Perimenopause



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


Results: Depressive Symptoms on CES-D Are Increased During Early Perimenopause in HIV-infected women who are ART naïve



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


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


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)


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.


Summary

• Studies of men do not inform us adequately about disease in women


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)

Washington D.C., USA, 22-27 July 2012www.aids2012.org43

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)


Thanks• WIHS collaborators

– Robert Kaplan– Pauline Maki– Michael Yin– Ruth Greenblatt

• WIHS participants


Photo Jonathan Wallen

aging, hiv and women

Documents

tnf alpha washington

hiv infectionmenopause

hiv womenmenopause

aids baseline719

aids diagnosis

aids unspecified hivaids

aidsfree baseline2124

inflammatory statehiv