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

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?

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

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%

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

How Common are Neuropsychiatric Comorbidities in HIV?

Number of Neuropsychiatric Comorbidities

Memory Problems

Depression Symptoms P<.001

HIV Dementia

Peripheral Neuropathy Symptoms

Severe Mental Illness

Alcohol Abuse P<.001

Drug Abuse P<.001

Do Neuropsychiatric Comorbidities Complicate Treatment?

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;12:255-266.

Do Neuropsychiatric Comorbidities Affect Survival?

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

Do Neuropsychiatric Comorbidities Affect Quality of Life?

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):220-233.

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

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

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

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

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

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