VACS Scientific Meeting 2010 Welcome & Overview

WELCOME Thank you for coming!

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

Who Are We?

National VACS Project Team 2008

West Haven/Yale VACS Project Team

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-A1069918), NIMH (P30-MH062294), 2009 ARRA award; and the Veterans Health Administration Office of Research and Development (VA REA 08-266) and Office of Academic Affiliations (Medical Informatics Fellowship).

What is VACS?

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

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

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)

Why Are We Here?

“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. 2005.

The VA is Ahead of the Curve

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

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

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

WHAT IS OUR PROGRESS?

As of August, 2009

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.

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.

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

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

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

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

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

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

AIDS Events are Variably Associated with CD4 and Survival By Median (IQR) CD4 By Relative Hazard of Death ART-CC, CID 2009;48:1138-51

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

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

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

LIVER Liver Injury in Veterans: Evaluation and Reduction

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

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

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

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

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

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

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

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

Website Updates: Dorothy Cohen

Migration to new VACS website January 2009 - 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

New VACS website

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

Cancer Core: For Robert Dubrow

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

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

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

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

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

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

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)

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)