1. Amy C. Justice, MD, PhD For the VACS Project Team
A Better Index of Mortality Risk: Combining HIV and “Non-HIV” Biomarkers
Amy C. Justice, MD, PhD
For the VACS Project Team

2. Veterans with HIV infection have…
More prevalent:
Liver disease
Renal disease
Pulmonary disease
Intracranial hemorrhage
Thrombosis
Cancer
Multi-morbidity
Less prevalent (maybe):
Obesity
Diabetes
Hyperlipidemia
Hypertension
Vascular disease
…than age/site/race matched uninfected veterans

3. Suspected Root Causes Substance use Viral hepatitis Treatment toxicity
More cigarettes, more drugs, similar alcohol
Viral hepatitis
More chronic Hepatitis C and B
Treatment toxicity
Antiretrovirals
Others (some “non-HIV”)
HIV infection
Chronic inflammation
Immune compromise, deregulation

4. Act in Concert, HIV Biomarkers Alone Do Not Capture Full Effect
Aging
Treatment Toxicity
HIV Progression
Substance Use and Other Behaviors

5. Developing a Unifying Index
HIV biomarker with
“Non-HIV” biomarkers

6. A Word on Biomarkers FIB-4
>3.25 for likely liver fibrosis/cirrhosis
<1.35 for unlikely liver fibrosis/cirrhosis
=age X AST /(platelets X Sqrt of ALT)
eGFR
<30 for stage IV renal insufficiency
=186.3 X creatinine X age X (1-(0.258 X gender)) X (1+(0.21 X black))

7. Development Set Nested Models (Poisson)
HIV Biomarkers
"Non-HIV" Biomarkers
Combined
(c stat=0.69)
(c stat=0.72)
(c stat=0.74)
CART
n=4813
IRR
95% CI
log VL>5 copies/mm3
1.28
1.12
1.45
1.16
1.02
1.33
CD cells/mm3
0.79
0.65
0.96
0.76
0.62
0.93
CD cells/mm3
0.70
0.59
0.84
0.71
0.85
CD cells/mm3
0.57
0.48
0.68
0.64
0.53
0.77
CD cells/mm3
0.45
0.37
0.54
0.46
0.69
AIDS Defining Diagnosis
1.55
1.37
1.76
1.44
1.26
1.64
Hemoglobin<10 g/dL
2.34
2.77
1.70
1.41
2.05
Hemoglobin g/dL
2.02
1.78
2.3
1.58
1.83
FIB
1.67
1.93
1.66
1.42
FIB4 <1.45
0.81
0.72
0.63
0.83
eGFR<30 ml/min
1.88
2.47
2.13
1.61
2.82
Viral Hepatitis
1.31
1.48
1.38
1.22
1.57
Development Set Nested Models (Poisson)
All models also adjusted for substance abuse and dependence and age.

8. Mortality by Quintiles of Estimated Risk

9. HIV and “Non-HIV” Markers
Percent
Quintiles of Mortality Risk Based on “Non-HIV” Markers Only

10. Biomarker Index by FIB-4
<1.45
>1.45
Age 50+ years %
21.0
40.6
<0.0001
Alcohol or Drug Ad or Ab %
26.3
37.3
CD4 cell count >350 %
46.6
30.7
Viral Load <5 log %
85.3
77.2
AIDS Free
80.0
74.4
Hemoglobin <12
17.7
26.0
Chronic Hepatitis B or C
34.8
63.9
eGFR<30
1.3
2.8

11. Limitations
Don’t know if changes in index equate to changes in mortality
Have not elucidated causal chain, e.g.
HIV to liver disease to death?
Liver disease to HIV progression to death?
Etc.

12. Conclusions Could be used to assess mortality risk
Could be used as a surrogate outcome
May inform prioritization of care

13. The VACS Project Team in West Haven, CT

14. Veterans Aging Cohort Study
PI and Co-PI: AC Justice, DA Fiellin
Scientific Officer (NIAAA): K Bryant
Participating VA Medical Centers: Atlanta (D. Rimland, C Jones-Taylor), 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, J Conigliaro, K Crothers, J Chang, S Crystal, N Day, J Erdos, M Freiberg, M Kozal, M Gaziano, M Gerschenson, B Good, A Gordon, J Goulet, M Hernan, K Kraemer, J Lim, S Maisto, P Miller, L Mole, P O’Connor, R Papas, H Paek, J Robins, C Rinaldo, M Roberts, J Samet, B Tierney, J Whittle
Staff: D Cohen, A Consorte, K Gordon, F Kidwai, F Levin, K McGinnis, M Rambo, J Rogers, M Skanderson, F Whitsett
Major Collaborators: Immunology Case Registry, Pharmacy Benefits Management, Framingham Heart Study, Women’s Interagency HIV Study, Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), Health Economics Research Center (HERC), Center for Health Equity Research and Promotion (CHERP), ART-CC, NA-ACCORD
Funded by: National Institute on Alcohol Abuse and Alcoholism (2U10 AA 13566); National Institute on Aging (K23 G00826); Robert Wood Johnson Generalist Faculty Scholar Award; an Inter-Agency Agreement between National Institute on Aging, National Institute of Mental Health, and the Veterans Health Administration; the VHA Office of Research and Development; and, VHA Public Health Strategic Health Care Group.