1. DoD-VA HIV Collaborations
Infectious Diseases Clinical Research Program
Uniformed Services University of the Health Sciences (USU) Department of Preventive Medicine and Biostatistics
DoD-VA HIV Collaborations
Brian Agan, MD
Deputy Science Director
VACS-COMpAAAS Scientific Meeting, 13 Dec 2016
A USU/DOD - NIAID Partnership
National Institute of Allergy and Infectious Diseases
Uniformed Services University, ‘America’s Medical School’

2. VACS Uniformed Services Workgroup
David Rimland, MD
Founding Director
Vincent Marconi, MD
Current Co-Director
Brian Agan, MD
Current Co-Director
Members: Sheldon Brown, Adeel Butt, Sarah Felter, Matt Freiberg, Anu Ganesan, Cynthia Gilbert, Matt Goetz, Kirsha Gordon, Grace Macalino, James Mancuso, Sarah Nagy, Tom O’Bryan, Jason Okulicz, KrisAnn Oursler, Mona Rai, Maria Rodriguez, Christina Schofield, Melissa Skanderson, Julie Womack, Seung Hyun Won

3. Current Project Areas Cost Effectiveness Continuum of Care
Outcomes Comparison – Guest PLoS ONE 2013
Covariate modeling – Rentsch PLoS ONE 2014
QALY comparison by CD4 initiation – Agan
SF6D vs QALY modeling – Rai/Won
CD4 modeling – Aldrete
Continuum of Care
Atlanta VAMC Continuum – Mangal ARHR 2014
Qualitative Saturation Methods – Hennink QHR 2016
Resilience in Veterans Predicts Retention – Wessinger submitted
Navigating VA care model – Hennink
Comparing retention in AVAMC to Grady – Fullard
Biomarker Studies
Longitudinal Biomarker Changes – So-Armah CHIVR 2014
Pre-HIV D-dimer predicts serious non-AIDS – Freiberg PLoS ONE 2016
HIV Biomarker Proteomics – Agan/Freiberg
Overlap Cohort
VACS Index – Won
Concepts in Development – DM, Hepatitis, Alcohol, CVD, Mental Health, Neuro

4. Infectious Diseases Clinical Research Program
Vision
To substantially reduce the impact of infectious disease in the military population through collaborative clinical research.
Mission
To conduct multicenter infectious diseases clinical research, focusing on high-impact cohort and interventional trials, to inform and improve care of the Warfighter.
Established Uniformed Services University of the Health Sciences (USU) and National Institute Allergy & Infectious Diseases (NIAID/NIH) Interagency Agreement
Chartered by ASD(HA) as a Tri-Service DoD research center at USU
Oversight by Executive and Operational Steering Committees (incl VA Rep)

5. Infectious Diseases Clinical Research Program
Tri-service Collaborative Clinical Research Partner Network
USU Research Center
Military hospitals and clinics (within US and overseas)
Military Medical Research Lab Commands (involved in ID research)
NIH, VA, Academia, and Industry collaborations
Centralized scientific and IRB review [established via MOU approved by ASD(HA), Service SGs, and USU President]
Programmatic regulatory compliance and monitoring
Centralized data management, specimen repositories, and statistical support
IDCRP Research Areas
Human Immunodeficiency Virus
Deployment / Travel-Associated Infections
Skin and Soft-Tissue Infections
Sexually Transmitted Infections
Emerging Infectious Diseases and Antimicrobial Resistance
Acute Respiratory Infections
Trauma-Related Infections

6. U.S. Military HIV Natural History Study
Ongoing prospective continuous enrollment observational cohort study
HIV+ DoD Active Duty & Beneficiaries >18 y/o
All subjects provide Informed Consent
Visits q6 months  clinical data + repositoried blood
Strengths of the cohort
Screened population
Racial diversity
Access to healthcare and medications
Stable socioeconomic status
Educated
Minimal substance abuse
Excellent follow-up
Approx 5950 enrolled, 3800 dated seroconverters, 1600 active
Median seroconversion: years (IQR )
Median time to enrollment: years (IQR )
Mean age at enrollment: years (SD 8.5 yrs)
Active duty at enrollment: 87.3%
Male gender: %

7. Biomarker 1 Specimen Selection Map:
Biomarker 1 Specimen Selection Map: (note that time axis is not consistent)
HIV+

9. HIV Biomarker Proteomics
Co-PIs: Agan, Freiberg, Ganz, Hsue
Population: HIV Seroconverters with Pre-HIV, Post-HIV, and Post-ART/VS samples (N=1240)
Data Sources:
HIV NHS: demographic, clinical, pharmacy, lab data; Post-HIV/ART samples
Military Health System: add’l clinical outcomes, pharmacy, lab data; Pre-HIV samples
SOMAscan (SomaLogic): 1130 plasma proteins at each time point
Specific Aims
Aim 1: To discover which protein biomarkers/protein biologic pathways are associated with HIV seroconversion
Aim 2: To discover which protein biomarkers/protein biologic pathways are and are not “affected ” by ART initiation and HIV viral suppression after HIV seroconversion
Aim 3: To determine if protein biomarkers/protein biologic pathways associated with HIV seroconversion, but not returned to pre HIV seroconversion levels with ART and viral suppression, are associated with future non-AIDS diseases and mortality

10. QALYs do not differ by CD4 at ART initiation (350-500 vs >500)
Objective: Evaluate longitudinal health state utility values (HSUV; surrogate for QALYs) as a measure of potential early ART benefit
Hypothesis: Longitudinal HSUV will differ by CD4 at ART initiation
Population: NHS and HAVACS HIV+ subjects with CD4>500 prior to ART and >1 yr f/u after
Outcome: HSUV with contributions from CD4, AIDS defining conditions, and non-AIDS defining conditions

11. Health State Utility Values

12. Combination of HSUV
Most subjects have multiple conditions associated with HSUV decrements – How to combine these?
Use the minimum HSUV (i.e. greatest decrement)
Mathematically combine the HSUV
Data
HSUV
Year
Non-AIDS Dx Code
Utility Value (UV)
From Method 1
From Method 2 1
509
0.76 2
150
0.97
0.745 3
127
0.844
0.672 4
231
0.90
0.641 5
121, 652
{0.81, 0.827}
0.543 6
109
0.79
0.496

14. DoD-VA HIV Collaborations: Next Steps
Cost Effectiveness
Use of SF-12/36 data to evaluate HSUV model
Addition of granular cost data  ICER analysis
Funding options: AHRQ, PCORI, DoD, VA
Continuum of Care
Transition of HIV care from DoD to VA
Joint analysis of longitudinal care continuum in DoD/VA (e.g. viral suppression at 5, 10, 15 years)
Biomarker Studies
Biomarker Proteomics
Cancer, CVD, others  We invite collaboration!

15. DoD-VA HIV Collaborations: Next Steps
Overlap Cohort
Update data set
Concepts for analyses: DM, Hepatitis, Alcohol, CVD, Mental Health, Neuro
Incorporate DoD HIV Virtual Cohort [in IRB review]
1743 Subjects (2012)

16. Acknowledgements USUHS / IDCRP NMCP VA / VACS CAPT Timothy Burgess
CDR Karl Kronmann
Amy Justice
David Tribble
Tahaniyat Lalani
Sheldon Brown
Grace Macalino
Susan Banks
Janet Tate
Daniel Rosenberg
Luca Illinik
David Rimland
Guido Pelaez
MAMC
Vincent Marconi
Seung Hyun Won
Matthew Freiberg
Christina Schofield
Xun Wang
Kaku So-Armah
Mary Fairchok
Morgan Byrne
Cynthia Baker
Tigiste Girma
Ramona Rai
TAMC
Meg Glancey
Emory
COL Tomas Ferguson
WRNMMC
Jodie Guest
LTC J. Hawley-Molloy
CAPT Timothy Whitman
Joseph Lipscomb
Emily Hui
Anuradha Ganesan
University of Vermont
DCC
David Wallace
Russell Tracy
Ed Parmelee
NMCSD
SPL
Xiuping Chu
CAPT Mary Bavaro
William (Chip) Bradley
Sheila Peel
Robert Deiss
Chris Olsen
Mark Manak
Nichol Kirkland
Pamela Wright
Janice Darden
SAMMC
Kimberly Blankenship
NIAID
LtCol Jason Okulicz
SAR
COL(Ret) Edmund Tramont
Thomas O’Bryan
Charlotte Rhodes
Sophia Siddiqui
Terry Sjoberg
Scott Merritt
John Powers