1. VACS Scientific Meeting 2010
Welcome & Overview

2. WELCOME
Thank you for coming!

3. Coffee, Bathrooms, Food, etc.
Orientation
Coffee, Bathrooms, Food, etc.

4. Who Are We?

5. National VACS Project Team 2008

6. West Haven/Yale VACS Project Team

7. Veterans Aging Cohort Study
PI and Co-PI: AC Justice, DA Fiellin
Scientific Officer (NIAAA): K Bryant
Participating VA Medical Centers: Atlanta (D. Rimland), 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, J Leung), Pittsburgh (A Butt, E Hoffman), and Washington DC (C Gibert, R Peck)
Core Faculty: K Mattocks (Deputy Director), S Braithwaite, C Brandt, K Bryant, R Cook, K Crothers, J Chang, S Crystal, N Day, J Erdos, M Freiberg, M Kozal, M Gaziano, M Gerschenson, A Gordon, J Goulet, K Kraemer, J Lim, S Maisto, P Miller, P O’Connor, R Papas, C Rinaldo, J Samet
Staff: D Cohen, A Consorte, K Gordon, F Kidwai, F Levin, K McGinnis, J Rogers, M Skanderson, J Tate, Harini, T Boran
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
Major Funding by: National Institutes of Health: NIAAA (U10-AA13566), NIA (R01-AG029154), NHLBI (R01-HL095136; R01-HL090342) , NIAID (U01-A ), NIMH (P30-MH062294), 2009 ARRA award; and the Veterans Health Administration Office of Research and Development (VA REA ) and Office of Academic Affiliations (Medical Informatics Fellowship).

8. What is VACS?

9. What is VACS? Observational study of veterans with and without HIV
8 Site in Depth Sample:>3,500 infected; >3,500 uninfected
National VA Sample: >40,000 infected: >80,000 uninfected
Uninfected are age/race/region matched to infected
Focused on the interactions of alcohol, aging, and related conditions on outcomes in HIV
Long term goal: improve health outcomes among HIV infected individuals through individually tailored and prioritized implementation strategies

10. Virtual Cohort (VC)
CURRENT DATA SOURCES: National administrative, laboratory, pharmacy, cancer registry, MI quality of care, and all cause mortality (requesting Medicare)
SUBJECTS: 41,753 HIV infected; 83,506 uninfected
All individuals with HIV diagnoses
Age, race/ethnicity, region 2:1 matched controls
Last updated: September, 2008
SITES: All VA sites
BASELINE: 1998 (11 years of follow up)
HIV infected veterans at initiation of HIV care
Controls selected and followed in same calendar year

11. VACS 8 BASELINE: 2002 (8 years) CURRENT DATA SOURCES (VC sources plus)
Consented for all clinical data
Records for sentinel events requested outside VA
All VA Electronic medical records including text fields
DNA and tissue bank
Annual self completed surveys
SUBJECTS: 3,600 HIV infected; 3,600 uninfected
Group matched: age, race/ethnicity, and site
SITES: Manhattan, Bronx, Washington DC, Baltimore, Pittsburgh, Atlanta, Houston, Los Angeles
BASELINE: 2002 (8 years)

12. Why Are We Here?

13. “By 2015, …50% of people living with HIV/AIDS [in the US] will be over 50 years of age.”
Aging Hearing: HIV over fifty, exploring the new threat.
Senate Committee on Aging. Washington, DC

14. The VA is Ahead of the Curve

15. This is Aging with a Twist
Heavy and prolonged substance use
Alcohol>Cigarettes>>Drugs
Hepatitis C and B Infection
“Return to health” with a vengeance
Underweight to overweight
Low cholesterol to high cholesterol
“Chronic inflammation”
ARV and non ARV treatment toxicity

16. Goals
To understand the roles of aging, comorbidity, treatment toxicity and substance use in determining morbidity and mortality with HIV infection
and
2. To use these insights to develop strategy interventions to improve patient outcomes

17. Three Guiding Assumptions
Aging, substance use, comorbidity, and treatment toxicity interact with HIV infection
Many of these interactions are modifiable
Strategies which individually tailor and prioritize care will be most effective

19. WHAT IS OUR PROGRESS?

21. As of August, 2009

22. VACS 8 Update FU 5* is currently in the field
39% complete among HIV infected
28% complete among uninfected
33% overall
Pulmonary study in the field (see talk)
Cardiovascular study in the field (see talk)
About to start pilot of serial sampling
*Denominator excludes those who have died or have not been seen at the local facility for 1 years.

23. DNA and Tissue Bank (Collection Completed 8/31/07)
HIV+
HIV-
Total
Unique Pts
1656
892
2548
DNA Samples
Tissue Samples
1542
867
2409
To collect serial samples on those newly initiating antiretroviral treatment in the future.

24. Active Core Support Grants
Period
K $
NIAAA U10: Alcohol in HIV+/- Veterans (Justice)
9/06-8/11
13,273
NIA/NHLBI RO1: Unexplained Anemia (Berliner)
12/06-11/10
1,635
VA Fellowship in Medical Informatics (Brandt)
7/06--
NHLBI R01: HIV-Associated Lung Disease (Crothers)
10/07-9/12
3,965
VA Merit: Returning OIF/OEF Veterans Cohort (Brandt)
1/08-12/11
900
NIAAA R01: Computer Simulation Alcohol & HIV Sub-Saharan Africa (Braithwaite)
2,210
VA HSR&D REAP: Pain Research, Informatics, Medical Comorbidities (Kerns)
10/08--
306
NHLBI R01: HIV(HCV) and CVD (Freiberg/Justice)
9/08-8/13
4,558

25. Career Development/Fellows Awards
Awardee
Source
Progress
Todd Kawecki
VA Informatics F.
Joining VA Informatics Leadership
Julie Womack
Applying for NINR RO1
Jason Sico
VA Neurology F.
Applying for RWJCS
Kristin Mattocks
AMFAR F.
Submitted VA VISN CDA
Kathleen Akgun
VA Pulmonary
Vincent LoRe
NIAID
In process
KrisAnn Oursler
NIA
Adeel Butt
NIDA
Submitted RO1s
Submitted R-21 (NIDDK)
Matthew Freiberg
NIAAA
NHLBI R01
Kristina Crothers
NIH/NCRR
NHLBI RO1
Scott Braithwaite
NIAAA, RWJFS
NIAAA R01
Shawn Fultz
VA HSR&D
Joined VHA Leadership

26. Active Collaborative Grants
Period
VA HSR&D: Medical Informatics Consortium (Samore)
10/08-9/12
NIMH P30: C. for Interdisc. Research on AIDS (Cleary)
9/01-6/13
NCI U01: NA-ACCORD (Moore)
7/07-6/11
Medical Research Council UK: ART-CC (Sterne)
2/08-2/11

27. Recent Publications 2009: 24 Scientific Publications
13 VACS original research
9 Cross Cohort original research
2 Invited editorials
As of: February 2010 (published/in press)
4 VACS, 1 Cross Cohort Collaboration
4 Invited editorials

28. Recent Highlights VACS Cross Cohort Collaboration
Clinical Cirrhosis endpoint arbitration
Non-AIDS malignancies
Fragility fractures
Cross Cohort Collaboration
NEJM and Lancet articles on When to Start
Variable impact of AIDS-defining Illnesses
Validation of the VACS Index in ART-CC, pending in NA-ACCORD

29. When To Start Controversy
ART-CC (Lancet)
NA-ACCORD (NEJM)
Used pre cART data to estimate events prior to cART initiation
Only adjusted for age
Found a survival benefit to starting >350, but not >500 vs. 350
Only included patients who entered care with CD4 counts>500
Used Marginal Structural Modeling to adjust for coun-founders in causal path
Adjusted for age, race, HCV infection, IDU
Found a survival benefit to starting >500 vs 350 than for >350 vs 200

30. AIDS Events are Variably Associated with CD4 and Survival
By Median (IQR) CD4
By Relative Hazard of Death
ART-CC, CID 2009;48:

31. This meeting will help decide…
Where are we going?
This meeting will help decide…

32. Come to the session tomorrow!
VACS Index Validation
Come to the session tomorrow!

33. Strategy Implementation Intervention
Prioritizing and Tailoring Care for Those At Greatest Risk of Alcohol Associated Adverse Outcomes

34. LIVER Liver Injury in Veterans: Evaluation and Reduction

35. Objective: Prevent Progression of Liver Disease and Death
Randomized Implementation Strategy Intervention
Prioritizes/stages evidence based care using
Screening for liver disease its common etiologies:
Alcohol
Viral hepatitis
Non adherence to antiretroviral treatment
Individual risk assessment, prioritization and staging of care employing:
behavioral therapy hazardous alcohol and non adherence
pharmacologic treatment for alcohol dependence and HCV infection
Behavioral support through HCV treatment
Using
Nurse case manager face to face and tele medical support
Electronic data entry and decision support

36. Importance
54% of HIV infected veterans have liver injury based upon biomarkers
Two thirds of these are infected with hepatitis C
the most common contributors to liver injury in this population are:
Alcohol use
Non adherence to antiretroviral treatment
Chronic viral hepatitis

37. Summary of Strategic Intervention
Brief Overview: The intervention to be tested in this site randomized trial among HIV infected veterans with evidence of liver injury (FIB 4>1.45) is an implementation strategy, coordinated by a nurse case manager, which systematically prioritizes and stages a menu of evidence based care modules including:
A staged behavioral and pharmacologic intervention for alcohol use
Detection and treatment of antiretroviral non adherence through pharmacy records and behavioral counseling
Detection and treatment of active HCV infection through screening, behavioral counseling, and specialty referral

38. Prioritization Strategy
We expect to detect multiple sources of liver injury in most individuals. When this occurs, a prioritization strategy will facilitate tailoring care to individual patients by incorporating:
Attributable patient risk using a prognostic index based on routine clinical biomarkers
Likely benefit using meta-analyses of the effect of evidence based treatments
Patient acceptability/preferences using standardized techniques of eliciting preferences for care

39. Risk Assessment Strategy
Based upon the validated VACS Risk Index using:
AST, ALT, platelets, hemoglobin, creatinine, and viral hepatitis titers to estimate risk of all cause mortality
Index and its components will be used to identify and illustrate level of risk as well as to chart progress over time

40. Work of this Meeting Review progress to date
Further plans for renewal grant due this fall
Advance our thinking about the intervention
Do we want to shift to emphasizing interventions most likely to improve risk of mortality rather than focusing on liver?
Have some fun together
Enjoy DC in the spring

41. Attention all speakers
Out of courtesy to the other speakers and the audience, PLEASE KEEP TO TIME

42. Attention Everyone
Please feel free to add to the discussion. We have gotten to where we are by listening to each other!

43. Website Updates: Dorothy Cohen

44. Migration to new VACS website
January Tridion SiteEdit – Yale content management system
More user friendly and functional website
New format:
Cohort characteristics
Data documentation
Library
Press/publicity
Publications (abstracts, posters, presentations, articles)
Investigators’ projects/specifications

45. New VACS website

46. Coming soon to the Website
Grants
Workgroups and committees
HIV Risk Index
CP/VC survey frequencies
ICD9 frequencies

47. Cancer Core:
For Robert Dubrow

48. Cancer Core Robert Dubrow (Chair) Sheldon Brown Adeel Butt
Cynthia Gibert
Matthew Goetz
Amy Justice
David Rimland
Maria Rodriguez-Barradas

49. Approved projects
Genetic risk factors for non-Hodgkin’s lymphoma in AIDS
Contributes DNA samples to a multi-center project, Charles Rabkin (NCI), P.I.
Antiretroviral therapy in relation to cancer incidence and survival in an HIV-Infected cohort

50. Validation of cancer diagnoses
NA-ACCORD ARRA Supplement
Contributed to development of the NA-ACCORD Cancer Data Collection System that will be used for validation of cancer endpoints by all participating cohorts
VACS 8
Linkage with VA Central Cancer Registry
Linkage with local cancer registries from 4 VACS sites
ICD-9 codes
Medical record review

51. Validation of cancer diagnoses (cont.)
Virtual Cohort
Linkage with VA Central Cancer Registry
ICD-9 codes
Cancer-type-specific algorithms developed from the VACS 8 validation

52. VACCR Cancer Diagnoses
Consented Cohorts
Total N: 8,001
Number of cancers: 921
Virtual Cohort
Total N: 121,782
Number of cancers: 9,704

53. VACCR Virtual Cohort Cancer Diagnoses
NHL
728 KS
473
Anal
350 HD
149
Liver
385
Prostate
2,185
Lung
1,485
Colorectal
649

54. Abstracts
HIV infection is an independent risk factor for lung cancer (CROI, oral presentation)
Trends in cumulative incidence of cancer among HIV-infected patients in North America (NA-ACCORD) (CROI, poster)
Risk of anal cancer in HIV-Infected patients and HIV-uninfected controls in North America (NA-ACCORD) (International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies [ICMAOI], oral presentation)

55. Abstracts (cont.)
Cervical cancer epidemiology among HIV-infected women in North America (NA-ACCORD) (ICMAOI, oral presentation)
Cervical cancer epidemiology among HIV-infected women in North America (NA-ACCORD) (International Papillomavirus Conference, oral presentation)
CD4 count trajectories of HIV-infected women in North America with cervical cancer after initiating HAART (NA-ACCORD) (XVIII International AIDS Conference, submitted)