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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 l.jpg

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 l.jpg
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


Learning objectives l.jpg
Learning Objectives

  • Common comorbid conditions in HIV

  • How comorbid conditions influence outcomes

  • Role of alcohol use/abuse as a comorbidity


Hiv aids timeline l.jpg
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


Hiv to aids to death l.jpg
HIV to AIDS to Death

AIDS-Defining Condition

HIV +

Death

8-10 yrs.

1-3 yrs.


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Median Years Survival with AIDS

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


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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



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Extrapolated Median Survival (Months) After AIDS 1994-97

Extrapolated from New England Journal of Medicine 1998;338:13;853-860


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Patient Outcomes in HIV in 2002

Aging

Comorbid Diseaseand Drug Toxicity

HIV

Access to

HIV Treatment


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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


Comorbidity l.jpg
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)


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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


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Example : Medical Comorbidity

  • Macrocytic anemia

    • HIV infection

    • Zidovudine and stavudine

    • Alcohol abuse


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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


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Functional Definition of Comorbidity

  • Any condition not included in the CDC list of AIDS defining conditions.



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HIV/AIDS Conditions

Provider-Reported (N = 810)

%


Slide19 l.jpg

General Medical Comorbidities

Provider-Reported (N = 811)

%


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Mean Comorbidity Counts (N = 810)

*P <0.001 based on Studentized T-test


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Distribution of HIV and General Medical Condition Counts

Provider-Report (N = 810)

%

Number of Conditions


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Mean Conditions Counts By CD4 Count /mm3 (N = 805)

*P < 0.001

*P = 0.77


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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


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Mean Counts By Age (N = 800)

*P < 0.001

*P = 0.22



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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



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How Important Is Comorbidity in HIV Infection?

  • Does it influence quality of life?

  • Does it complicate treatment?

  • Does it influence survival?



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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



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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



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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


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Provider-Reported Illness SeverityComorbidity-Regressions(N = 800)

†Separate regressions for HIV and general medical comorbidities; adjusted for age, race. and CD4 count



Slide37 l.jpg

Effects of Substance Use/Abuse

Psychiatric

Medical

Bone Marrow Suppression

Depression

Nonadherence

Hepatitis

Addiction

Risky Sexual Behaviors



Icd 9 diagnoses of substance abuse l.jpg
ICD-9 Diagnosesof Substance Abuse

40

37%

35

30

25

21%

20

15

10

5

0

Drug Abuse

Alcohol Abuse


Slide40 l.jpg

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


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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



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Are Providers Aware of Alcohol Use?

57%

13%

63%

0.14

Patient ever drank

Patient currently drinks

Agreement (patient)

Kappa


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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”?


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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


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What Can Be Done?

  • Behavioral Interventions with providers and patients

  • Targeted computer reminders


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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)


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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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