2. 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

3. 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

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

5. HIV/AIDS Timeline 1981198919961998 AIDS 1st Recognized 198719921984 Test for HIV AZT Multidrug Rx Protease Inhibitors (HAART) Prevention for PC Pneumonia 2002

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

7. Median Years Survival with AIDS CD4 Count (mm3) Prior to HAART (‘92-95’) Post HAART Short Term Extrapolation Estimation Adjusted for Aging and Rx Failure >2009.1134.615.5 <2003.218.58.7 <5017.55.5 King et al Long-Term HIV/AIDS Survival Estimation in the HAART Era. Under review.

8. 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

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

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

11. Patient Outcomes in HIV in 2002 Access to HIV Treatment HIV Aging Comorbid Disease and Drug Toxicity

12. 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

13. 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)

14. 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

15. Example : Medical Comorbidity Macrocytic anemia –HIV infection –Zidovudine and stavudine –Alcohol abuse

16. 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

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

18. How Common is Major Medical Comorbidity in HIV?

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

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

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

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

23. Mean Conditions Counts By CD4 Count /mm 3 (N = 805) *P < 0.001 *P = 0.77

24. General Medical Comorbidity By Age 0 5 10 15 20 25 30 35 40 HTNHyper- lipidemia DMStrokePacrea- titis CancerMI/CADCHFPVD <50 Yrs 50+ Yrs P<.05 in all cases

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

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

27. Cognitive Dysfunction* by Age *Provider-report 0 5 10 15 20 25 30 35 40 20-2930-3940-4950-5960+ Cognitive Impairment?AIDS Dementia %

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

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

30. Comorbidity and Quality of Life

31. SF-12 Scores Comorbidity 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

32. Comorbidity and Hospitalization

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

34. Comorbidity and Survival

35. 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

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

37. Special Role of Substance Use

38. Effects of Substance Use/Abuse Nonadherence Hepatitis Addiction PsychiatricMedical Risky Sexual Behaviors Depression Bone Marrow Suppression

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

40. ICD-9 Diagnoses of Substance Abuse 37% 21% 0 5 10 15 20 25 30 35 40 Drug AbuseAlcohol Abuse

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

42. 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

43. How Common is Alcohol Use/Abuse (HIV+ Veteran Report) Drinks alcohol86% Drinks currently40% AUDIT (  8) 33% > 6 drinks one occasion33%

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

45. 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”?

46. VACS 5 & Alcohol: Specific Aims 1)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

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

48. Veterans Aging Cohort Study Center (Pittsburgh) 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

49. VACS Sites PIs and CoPIs 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)