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The Role of Comorbidity in Determining Outcomes in HIV

The Role of Comorbidity in Determining Outcomes in HIV. Amy C. Justice, MD, PhD Grand Rounds University of Pittsburgh School of Medicine February 1, 2002. Topics To Be Covered. HIV/AIDS Treatment and Survival Definitions of Comorbidity Prevalence of Comorbidity in HIV

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The Role of Comorbidity in Determining Outcomes in HIV

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  1. The Role of Comorbidity in Determining Outcomes in HIV Amy C. Justice, MD, PhD Grand Rounds University of Pittsburgh School of Medicine February 1, 2002

  2. Topics To Be Covered • HIV/AIDS Treatment and Survival • Definitions of Comorbidity • Prevalence of Comorbidity in HIV • Medical Comorbidity and Outcomes • Psychiatric Comorbidity and Outcomes • Alcohol and Outcomes

  3. Learning Objectives • Common comorbid conditions in HIV • How comorbid conditions influence outcomes • Role of alcohol use/abuse as a comorbidity

  4. HIV/AIDS Timeline Protease Inhibitors (HAART) Prevention for PC Pneumonia AIDS 1st Recognized AZT Multidrug Rx Test for HIV 1981 1984 1987 1989 1992 1996 1998 2002

  5. HIV to AIDS to Death AIDS-Defining Condition HIV + Death 8-10 yrs. 1-3 yrs.

  6. Median Years Survival with AIDS King et al Long-Term HIV/AIDS Survival Estimation in the HAART Era. Under review.

  7. Not All Equally Benefit From Rx • Gaps in Survival • by Age • by Insurance Status • Suggest differences in • Access, adherence to treatment • Comorbid medical/psychiatric disease • Susceptibility to treatment toxicity

  8. Median Survival (Months) with AIDS by Age 1981-1992 Research on Aging 1998;665-685

  9. Extrapolated Median Survival (Months) After AIDS 1994-97 Extrapolated from New England Journal of Medicine 1998;338:13;853-860

  10. Patient Outcomes in HIV in 2002 Aging Comorbid Diseaseand Drug Toxicity HIV Access to HIV Treatment

  11. Strict Definition of Comorbidity “Many…elements of illness may be due to … other diseases… [than the disease under study]. The associated illness arising from these other diseases produces a co-morbidity that may affect … prognosis and therapeutic response…” AR Feinstein, Clinical Judgment, 1967

  12. Comorbidity • May be • Medical or psychiatric • Exacerbated by “primary disease” • May exacerbate “primary disease” • But, is not caused by “primary disease” • Treating primary disease will not treat the comorbidity (may exacerbate comorbidity)

  13. Identifying Role of Comorbidity Difficult to know whether condition is Caused by “primary disease” Toxicity from treatment for “primary disease” “Independent” of “primary disease” Must study those with/without primary disease Etiology of condition may facilitate treatment

  14. Example : Medical Comorbidity • Macrocytic anemia • HIV infection • Zidovudine and stavudine • Alcohol abuse

  15. Example: Psychiatric Comorbidity • Depression • Situational depression associated with dx of HIV • Antiretrovirals associated with depression • HIV risk behaviors (substance abuse and sex with multiple partners) associated with depression

  16. Functional Definition of Comorbidity • Any condition not included in the CDC list of AIDS defining conditions.

  17. How Common is Major Medical Comorbidity in HIV?

  18. HIV/AIDS Conditions Provider-Reported (N = 810) %

  19. General Medical Comorbidities Provider-Reported (N = 811) %

  20. Mean Comorbidity Counts (N = 810) *P <0.001 based on Studentized T-test

  21. Distribution of HIV and General Medical Condition Counts Provider-Report (N = 810) % Number of Conditions

  22. Mean Conditions Counts By CD4 Count /mm3 (N = 805) *P < 0.001 *P = 0.77

  23. General MedicalComorbidity By Age 40 <50 Yrs 35 50+ Yrs 30 25 20 15 10 5 0 HTN Hyper-lipidemia DM Stroke Pacrea-titis Cancer MI/CAD CHF PVD P<.05 in all cases

  24. Mean Counts By Age (N = 800) *P < 0.001 *P = 0.22

  25. How Common is Neuro-Psychiatric Comorbidity in HIV?

  26. Cognitive Dysfunction* by Age Cognitive Impairment? AIDS Dementia 40 35 30 25 % 20 15 10 5 0 20-29 30-39 40-49 50-59 60+ *Provider-report

  27. Prevalence of Mental Disorders (3 year) in VACS 3

  28. How Important Is Comorbidity in HIV Infection? • Does it influence quality of life? • Does it complicate treatment? • Does it influence survival?

  29. Comorbidity and Quality of Life

  30. SF-12 ScoresComorbidity Regressions(N = 759) †Separate regressions for HIV and general medical comorbidities; and for SF-12 physical and mental health scores; adjusted for age, race, and CD4 count

  31. Comorbidity and Hospitalization

  32. Inpatient Admissions: Zero InflatedPoisson Regression *Adjusting for age, race, CD4 count, viral load, ART, CES-D score **Includes Toxoplasmosis, Histoplasmosis, and Coccidiomycosis Log Likelihood = -796

  33. Comorbidity and Survival

  34. Survival: Cox Proportional Hazards Model (N=761) *Adjusting for age, race, CD4 count, viral load, ART, CES-D score **Includes Toxoplasmosis, Histoplasmosis, and Coccidiomycosis C Statistic = 0.82

  35. Provider-Reported Illness SeverityComorbidity-Regressions(N = 800) †Separate regressions for HIV and general medical comorbidities; adjusted for age, race. and CD4 count

  36. Special Role of Substance Use

  37. Effects of Substance Use/Abuse Psychiatric Medical Bone Marrow Suppression Depression Nonadherence Hepatitis Addiction Risky Sexual Behaviors

  38. How Common is Substance Use/Abuse in HIV?

  39. ICD-9 Diagnosesof Substance Abuse 40 37% 35 30 25 21% 20 15 10 5 0 Drug Abuse Alcohol Abuse

  40. Substance Use * Pt. Current 100 Pro. Current 90 Pt. Ever 80 70 Pro. Ever 60 % 50 40 30 20 10 0 Illicit Drugs Alcohol *Patient and Provider Report

  41. Why is Alcohol of Special Concern? • Risky sexual behavior • Nonadherence to antiretroviral therapy • Increased susceptibility to ADRs • liver injury • Peripheral red cell destruction • bone marrow injury • Susceptibility to CNS injury • Susceptibility to immune dysfunction

  42. How Common is Alcohol Use/Abuse (HIV+ Veteran Report)

  43. Are Providers Aware of Alcohol Use? 57% 13% 63% 0.14 Patient ever drank Patient currently drinks Agreement (patient) Kappa

  44. What do we Need to Know? • Does alcohol exacerbates HIV progression or associated conditions? • Does alcohol mitigate effectiveness and increases toxicity of antiretroviral treatment? • Does HIV infection increase the risk of common complications of alcohol? • What level of alcohol consumption is “safe”?

  45. VACS 5 & Alcohol: Specific Aims • Influence of alcohol consumption on laboratory measures and patient outcomes among veterans with/without HIV infection and hepatitis C 2) Provider awareness of and attitudes about alcohol consumption among their patients 3) Patient awareness and attitudes toward alcohol consumption

  46. What Can Be Done? • Behavioral Interventions with providers and patients • Targeted computer reminders

  47. Alcohol Faculty Joseph Conigliaro (Co PI) Nancy Day Adam Gordon Robert Cook Kevin Kramer Faculty Charles Rinaldo John Mellors Scott Braithwaite Adeel Butt Shawn Fultz (GIM Fellow) Gabriel Silverman (MS I) Staff Tamra Madenwald Susan Smola Kathleen McGinnis Joseph Wagner Melissa Skanderson Elaine Lasky Rose Pfeuffer Sonia Bhatt Jerome Lee Veterans Aging Cohort Study Center (Pittsburgh)

  48. Los Angeles, CA Matthew Goetz David Leaf Kurt Willis (Coord) Manhattan/Brooklyn, NY Michael Simberkoff David Blumenthal Joseph Leung Cathryn Mancini (Coord) Darlene Chavis (Asst) Atlanta, GA David Rimland (PI) Cedrella Jones-Taylor (Co PI) Laura Gallaher (Coord) Stephanie Grupinski (Asst) Bronx, NY Sheldon Brown (PI) Sarah Garrison (Co PI) Peying Xao (Coord) Katherine Elliot (Asst) Houston , TX Maria Rodriguez-Barradas (PI) Alain Bouckenooghe (Co PI) Deborah Terry (Coord) Cythia Rose (Asst) VACS Sites PIs and CoPIs

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