Women, Aging and HIV. Julie Womack, CNM, APRN, PhD Yale School of Nursing VHA Connecticut, West Haven. Slide 1

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1 Slide 1 Women, Aging and HIV Julie Womack, CNM, APRN, PhD Yale School of Nursing VHA Connecticut, West Haven

2 Slide 2 History and Medications History 68 years old HIV+ since 1987 Anemia Osteoporosis Gastroesophageal reflux disease Osteoarthritis Medications Lopinavir/ritonavir + tenofovir/emtricitabine Ibandronate Vitamin D Calcium, Magnesium Proton pump inhibitor NSAIDS Morphine

3 Social History and Functional Slide 3 Status Social History Lives alone On disability Functional Status Frail Painful movement Unstable gait uses a cane Requires help with housework/shopping Cognitively intact

4 Slide 4 Physical Exam and Laboratory Physical exam/vital Signs BMI 16.5 kg/m 2 Pain 8/10 VACS Index Risk 30% mortality in 5 years Laboratory/Radiology CD4 450 cells/mm 3 36% HIV RNA< 40 copies/mm 3 Hemoglobin 10.5 g/dl DXA T-scores Lumbar spine -3.7 Total hip -3.8 Justice et al. CID, in press

5 Slide 5 Mary: Goals for Care Maintain her level of mobility Preserve cognitive function Manage her pain

6 Slide 6 Outline The aging of the epidemic HIV Multimorbidity Comorbid conditions Anemia Decreased bone mineral density Management

7 Slide 7 The Aging of the Epidemic

8 Projected Proportion of those Living With HIV in United States 50+ Years* Slide 8 17% 19% 21% 22% 25% 27% 27% Projected 35% 33% 29% 37% 39% 41% 44% 45% 47% 50% *Data from 2008, onward projected based on trends (calculated by Justice, AC), data from CDC Surveillance Reports 2007

9 Slide 9 Women 45+ and 50+ Years in Observational Cohorts (%) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Total N = 7,065 > 45 years > 50 years 79% 61% 61% 66% 55% 42% KPNC VACS-VC WIHS NA-ACCORD N= 680 N= 1,000 N= 1,385 N= 4,000

10 Life Expectancy Slide 10 General population (HIV-) Men Women Delta A 20 yr old will live to (years) A 35 yr old will live to (years) HIV+ at HAART initiation Men Women Delta A 20 yr old will live to (years; adjusted) A 35 yr old will live to (years; adjusted) Adapted from Antiretroviral Therapy Cohort Collaboration (ART-CC), Lancet 2008;372:293-99;

11 Slide 11 Life Expectancy Why do HIV+ individuals on HAART not have a normal life expectancy? Why are women are more disadvantaged than men?

12 Immunosenescence and HIV Slide 12 T cell compartment most disrupted Thymus involution Naïve and memory T cells Decreased number Decreased functionality Memory cells Proinflammatory cytokines Early mortality in the elderly More rapid progression to AIDS in HIV+ No data on gender differences Effros et al. 2008, CID. 47:

13 Multimorbidity and HIV in Slide 13 the ALIVE Cohort Percent HIV- HIV (N = 1262) Salter et al., CID. 53: Number of Multimorbid Conditions Diabetes, obstructive lung disease, liver disease, anemia, obesity, kidney dysfunction, and hypertension

14 Slide 14 Summary HIV+ individuals do not have normal lifespan even with HAART Chronic inflammation related to HIV Multimorbidity Women are particularly disadvantaged Multimorbidity HIV HAART Traditional risk factors

15 Slide 15 Anemia

16 Slide 16 Anemia Early in the Epidemic Severe Causative factors Untreated HIV Opportunistic infections AZT use Berhane et al., JAIDS. 37: ; Shah et al., HIV Medicine. 8:38-45.

Anemia and Survival Slide 17 2003 by the Infectious Diseases

17 Anemia and Survival Slide by the Infectious Diseases Society of America Lundgren & Mocroft, CID. 37:S297-S303

18 Anemia in the HAART Era Slide 18 HAART: protection against anemia 30% HIV+ individuals are anemic Mild, multifactorial Greatest risk Women, Blacks, IDU and older individuals Associated with decreased survival Berhane et al., JAIDS. 37: ; Shah et al., HIV Medicine. 8:38-45; Berhane et al., JAIDS. 26:28-35; Sullivan et al., Blood. 91: ; Moore et al., JAIDS. 19:29-33; Moore et al., JAIDS, 29:54-57; Semba et al., CID, 34: ; Lundgren & Mocroft, CID, 37:S297-S303.

19 Slide 19 SMART Study Anemia and Survival 2000 individuals, 28% women Anemia Women: < 12 g/dl Men: < 14 g/dl Patients with current anemia had a significantly increased risk of death IRR 2.19 ( ) Mocroft et al., 10 th International Congress on Drug Therapy in HIV Infection, P144, 2010.

20 Anemia in the Elderly Slide 20 General Population Reduced physical performance Fatigue, functional dependence, disability Declining muscle strength and density Declining executive function and cognitive impairment particularly in older women Increased risk of falls and frailty Roy, Clinics in Geriatric Medicine, 27:67-78;Vanesse et al., Hematology, 2010: ; Tinetti et al., NEJM, 348:42-9.

21 Slide 21 Anemia vs Goals for Care Goals for care Maintain her level of mobility Preserve cognitive function Manage her pain Anemia is key

22 Slide 22 Where Can We Intervene? HIV-specific/Traditional causes Intervention HIV not fully suppressed Evaluate adherence Tenofovir-related renal insufficiency Routine causes Inflammation HIV Multiple chronic diseases Aging Evaluate creatinine and egfr If indicated, new regimen not including tenofovir Rule out all routine? Price & Schrier, Advances in Hematology, 2010:508739; Deeks Annual Review of Medicine, 62: ; Ferrucci & Balducci, Seminars in Hematology. 45: ; Buskin & Sullivan, Transfusion, 44:

23 Slide 23 Decreased Bone Mineral Density

24 Slide 24 Osteoporosis Odds of osteoporosis (T-score -2.5) in HIV-infected patients compared with HIV-uninfected controls Brown & Qaqish AIDS. 20:

25 BMD in ART-Treated Individuals Slide 25 Bolland M J et al JCEM. 96: by Endocrine Society

26 Slide 26 Subsequent Questions Will this trend continue in individuals treated earlier in the course of their disease? BMD over time in older women? What are modifiable risk factors? How does this translate into fragility fractures, particularly in older women?

27 Incidence of fragility fractures Male Veterans Slide 27 Age >= 50 years Age at first fracture Unadjusted fracture incidence HIV+ N=40,426 HIV- N=78,474 34% 34% NA 54 years 53 years /1,000 person/years 1.0/1,000 person/years P First hip, vertebral, humoral fractures N=1615 Womack et al., PLoS ONE, 6:e17217

28 Fragility Fracture Models Unadjusted model HR (95% CI) Full model HR (95% CI) Slide 28 HIV-infected only model HR (95% CI) HIV 1.32 (1.20, 1.47) 1.10 (0.97, 1.25) Age (10 yr increments) 1.32 (1.25, 1.40) 1.52 (1.39, 1.66) White 1.80 (1.60, 2.03) 1.85 (1.52, 2.25) Alcohol use disorder 1.80 (1.50, 2.17) 1.50 (1.12, 2.02) Liver disease 1.38 (1.10, 1.73) 1.39 (1.03, 1.87) Current corticosteroids 1.45 (1.21, 1.74) 1.41 (1.06, 1.88) Smoker 1.21 (1.04, 1.42) 1.30 (1.00, 1.67) Any PPI use 1.70 (1.51, 1.92) 1.55 (1.28, 1.89) BMI 0.82 (0.79, 0.85) 0.87 (0.77, 0.99) BMI (1.000, 1.003) (1.000, 1.005) CD4/100 cells/mm (0.98, 1.05) Current TDF use 1.29 (0.99, 1.70) Current PI use 1.41 (1.16, 1.70) Also controlled for: congestive heart failure, pulmonary disease, peripheral vascular disease, drug abuse, major depressive disorder, CAD, diabetes, liver disease, renal insufficiency, osteonecrosis, steroid use at baseline. Adjustment for non-proportionality: HIV*log(time) HR: 1.09 (95% CI: 1.01, 1.18)

29 Slide 29 Fragility Fractures in Women

30 Etiologies: HIV and Fragility Slide 30 HIV Fracture Uncoupling of bone formation and resorption Direct effect of virus TNFα Modifiable traditional risk factors Falls?

31 Slide 31 Osteoporosis vs Mary s Goals for Care Goals for care Maintain her level of mobility Preserve cognitive function Manage her pain Fracture risk key

32 Slide 32 HIV-Specific Risk Factors Fully suppressive HAART decreases Effects of virus on bone Effects of inflammation Mary s HIV-RNA < 40 copies Stable HAART leads to stable BMD Yin, MT & Shane, E Current Opinion in Endocrinology and Diabetes. 13: ; Bolland MJ et al JCEM. 96:

33 Where Can We Intervene? Slide 33 Traditional, modifiable risk factors Low BMI: 16.5 kg/m 2 Pain and Mobility Proton-pump inhibitor use Treat severe bone loss Intervention Prevent further weight loss Incorporate non-pharmacologic therapies Decrease dose of opiates Increase muscle mass and strength Improve gait Decrease risk for falls Re-evaluate severity of GERD Consider discontinuing treatment or exchanging for calcium-based antacid Continue ibandronate

34 Conclusion Slide 34 HIV life expectancy < general population Women particularly disadvantaged HIV and multimorbidity Role in women Causes of multimorbidity are multifactorial Are risk factors different for women Anemia and BMD More prevalent in women

35 Slide 35 National VACS Project Team Presented at the 2nd International Workshop on HIV & Women, 9 10 January 2012, Bethesda, MD, USA

Veterans Aging Cohort Study Slide 36 Consortium PI : AC Justice* Scientific Officer (NIAAA): K Bryant Affiliated PIs: N Berliner, S Braithwaite, K Crothers*, DA Fiellin*, M Freiberg*, V LoRe*

36 Veterans Aging Cohort Study Slide 36 Consortium PI : AC Justice* Scientific Officer (NIAAA): K Bryant Affiliated PIs: N Berliner, S Braithwaite, K Crothers*, DA Fiellin*, M Freiberg*, V LoRe* Participating VA Medical Centers: Atlanta (D. Rimland*, J Guest), Baltimore (KA Oursler*, R Titanji), Bronx (S Brown, S Garrison), Houston (M Rodriguez-Barradas, N Masozera), Los Angeles (M Goetz, D Leaf), Manhattan-Brooklyn (M Simberkoff, D Blumenthal, H Leaf, J Leung), Pittsburgh (A Butt, E Hoffman), and Washington DC (C Gibert, R Peck) Core and Workgroup Chairs: C Brandt, R Dubrow, N Gandhi, J Lim, K McGinnis, C Parikh, J Tate, E Wang, J Womack Staff: H Bathulapalli, T Bohan, J Ciarleglio, D Cohen, A Consorte, P Cunningham, A Dinh, L Erickson, C Frank, K Gordon, J Huston, F Kidwai-Khan, G Koerbel, F Levin, M Mezes, L Piscitelli, C Rogina, S Shahrir, M Skanderson, A Varcas Major Collaborators: VA Public Health Strategic Healthcare Group, VA Pharmacy Benefits Management, Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Yale Center for Interdisciplinary Research on AIDS (CIRA), Center for Health Equity Research and Promotion (CHERP), ART-CC, NA-ACCORD, HIV-Causal Cross Cohort Collaborators: Richard Moore (NA-ACCORD), Jonathan Stern (ART-CC), Brian Agan (DoD) Major Funding by: National Institutes of Health: AHRQ (R01-HS018372), NIAAA (U10-AA13566, U24-AA020794, U01-AA020790), NHLBI (R01-HL095136; R01-HL090342; RCI-HL100347), NIA (R01-AG029154), NIAID (U01-A ), NIMH (P30-MH062294), and the Veterans Health Administration Office of Research and Development (VA REA , VA IRR Merit Award) and Office of Academic Affiliations (Medical Informatics Fellowship) *Indicates individual is also the Chair of a Core or Workgroup

Aging with HIV: Multimorbidity, Risk Assessment, and Personalized Health Care

Aging with HIV: Multimorbidity, Risk Assessment, and Personalized Health Care Amy C. Justice, MD, PhD Professor of Medicine and Public Health Yale University Section Chief, General Internal Medicine VA