1. for the VACS Project Team
Medical and NeuroPsychiatric Comorbidity in HIV Infection and Its Association with Patient Outcomes ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Amy C. Justice, MD, PhD
Kathleen A. McGinnis, MS
Joseph W. Wagner, MPH
Joseph Conigliaro, MD
Linda Rabeneck, MD
for the VACS Project Team

2. How Important are Neuropsychiatric Comorbidities in HIV
How common are they?
Do they complicate treatment?
Do they influence survival?
Do they affect quality of life?

3. Veterans Aging Cohort 3 Site Study (VACS 3) ~~~~~~~~~~~~~~~~~~~~~~~~~
Funded by Robert Wood Johnson Foundation and National Institute of Aging
Enrolled 881 veterans with HIV infection
July 1999 to August 2000
At 3 VA sites: Cleveland, Manhattan, Houston
Of HIV+ patients seen in the clinics, 85% enrolled
Data
Patient and provider surveys
Electronic medical records
To date 83 deaths

4. Characteristics of VACS 3
(n=881)
Median Age (range)
50 years (29-79)
Age > 50 years
42%
Gender
Male
Female
99% 1%
Race
White
African-American
Hispanic and other
33%
54%
12%
HIV Risk Factor
MSM
Heterosexual
IVDU
37%
24%

5. Neuropsychiatric Variables
Memory
Problems
Patient reported trouble remembering
Depression Symptoms
Patient completed Center for Epidemiologic Studies Depression Scale (CESD)*
HIV Dementia
Provider reported that patient ever had HIV dementia
Peripheral Neuropathy Symptoms
Patient report of bothersome pain or numbness in hands and feet
Severe Mental Illness
ICD-9 codes for patient having manic depression/bipolar disorder or schizophrenia
Alcohol Abuse
ICD-9 codes for alcohol abuse or dependence
Drug Abuse
ICD-9 codes for drug abuse or dependence
These are not state of the art measures of neurocognitive function. However, these measures are useful for hypothesis generating. We did do formal neurocognitive testing in VACS 5 and those data will be available or analysis soon.
CESD had good sensitivity and specificity for detecting symptoms of depression.
The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) is based on the World Health Organization's Ninth Revision, International Classification of Diseases (ICD-9). ICD-9-CM is the official system of assigning codes to diagnoses and procedures associated with hospital utilization in the United States.
*Andreson E, Malmgren J, Carter W, PatrickD. Screening for depression in well older adults: evaluation of a short form of the CES-D. Am J Prev Med 1994;10:77-84

6. How Common are Neuropsychiatric Comorbidities in HIV?

7. Number of Neuropsychiatric Comorbidities

8. Memory Problems

9. Depression Symptoms
P<.001

10. HIV Dementia

11. Peripheral Neuropathy Symptoms

12. Severe Mental Illness

13. Alcohol Abuse
P<.001

14. Drug Abuse
P<.001

15. Do Neuropsychiatric Comorbidities Complicate Treatment?

16. Adherence to HIV Medication
Memory Problems
Depression
Symptoms
HIV Dementia
Peripheral Neuropathy
Severe Mental Illness
Alcohol Abuse
Drug Abuse
% “Perfectly” Adherent
yes no
Missed no doses in past 4 days 65 71 64 69 68 59 72 63 66 70
Did not miss any meds last weekend 74 80 82 77 78 75
Never missed any HIV meds 23 31 27 29 22 28 26 24
Statistically significant differences shown in red (p<0.05)
ARVs – on any NNRTIs, NRTIs, or PIs
NRTI – nucleotide reverse transcript inhibitors - reduce growth of HIV
NNRTI – non-nucleotide reverse transcript inhibitors - Keep HIV from copying DNA
PI – Protease Inhibitors – interferes with ability to assemble itself
Note: Adherence questions from: Chesney MA, Ickovics JR, Chambers DB, Gifford AL, Neidig J, Zwickl B, et al. Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: the AACTG Adherence Intstruments. AIDS Care 2000;12:

17. Do Neuropsychiatric Comorbidities Affect Survival?

18. Survival Univariate Multivariate* Comorbidity Hazard Ratio p
Memory Problems
.72 .2
.53
.012
Depression Symptoms
1.69
.02
1.82
.014
HIV Dementia
1.09 .9
1.18 .7
P. Neuropathy Symptoms
1.60
.04
1.59
.06
Severe Mental Illness
1.20 .6
1.16
Alcohol Abuse
1.43
.12
1.45
Drug Abuse
1.21 .4
.96
*also adjusted for age, CD4, and viral load

19. Do Neuropsychiatric Comorbidities Affect Quality of Life?

20. Health Related Quality of Life ~~~~~~~~~~~~~~~~~~~~~~~~~
Based on the Short Form-12 from baseline patient survey
A standard instrument used for measuring Health Related Quality of Life
Uses standardized scoring methods to create:
Physical Health Composite Score
Mental Health Composite Score
Scores range from 0 for worst health to 100 for best health
These scores have been shown to have excellent precision and reliability for the summary scores generated by the longer instrument (SF-36).8
These were scored using established methods. The scores range from 0 for worst health to 100 for best health.
1Ware JE, Kosinski M, Keller SD. A 12-item Short-Form Health Survey. construction of scales and preliminary tests of reliability and validity. Medical Care 1996; 34(3):

21. Physical HRQOL Univariate Multivariate* Comorbidity Coef. p
Memory Problems
-5.97
<.001
-3.43
Depression Symptoms
-6.31
-3.91
HIV Dementia
-3.47
.03
-1.50 .3
P. Neuropathy Symptoms
-6.05
-3.58
Severe Mental Illness
-2.01
.06
-.68 .5
Alcohol Abuse
-2.68
-1.41 .1
Drug Abuse
-1.89
.006
.44 .6
*also adjusted for age, CD4, and viral load
Those with cancer score about 9 points lower than healthy people
Those allergies and asthma score about 3-4 points lower than healthy people

22. Mental HRQOL Univariate Multivariate* Comorbidity Coef. p
Memory Problems
-7.34
<.001
-2.16
Depression Symptoms
-13.67
-12.42
HIV Dementia
.48 .8
-1.18 .4
P. Neuropathy Symptoms
-5.35
-.55
Severe Mental Illness
-3.04
.002
.15 .9
Alcohol Abuse
-4.02
-1.11 .2
Drug Abuse
-3.71
-.18
*also adjusted for age, CD4, and viral load

23. Limitations ~~~~~~~~~~~~~~~~~~~~~~~~~
Inadequate psychiatric and cognitive assessments
Neuropsychiatric testing has been conducted in VACS 5 Site Feasibility Study in collaboration with the HIV Neurobehavioral Research Center (HNRC)
No HIV negative controls
Few women
Limited size and short follow-up interval

24. Summary ~~~~~~~~~~~~~~~~~~~~~~~~~
Neuropsychiatric comorbidities are common in persons with HIV
Those with memory problems, depression symptoms, peripheral neuropathy symptoms, and who have abused drugs are less likely to be “perfectly” adherent

25. Summary ~~~~~~~~~~~~~~~~~~~~~~~~~
Memory problems, depression symptoms and peripheral neuropathy symptoms
negatively associated with physical HRQOL
negatively associated with survival (except memory problems)
Memory problems and depression symptoms
negatively associated with mental HRQOL

26. Website ~~~~~~~~~~~~~~~~~~~~~~
Special thanks to the participating veterans and
the sites (Cleveland, Manhattan, and Houston)