Transcript Care at the Close of Life: Evidence and Experience

Overcoming the False Dichotomy of
Curative vs Palliative Care for
Late-Stage HIV/AIDS
Michael W. Rabow, MD
Education Guides Editor
Care at the Close of Life: Evidence and Experience
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HIV/AIDS
“Let me live the way
I want to live, until I can’t.”
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
Mr C’s Story
• A 33-year-old man with advanced human
immunodeficiency virus (HIV) infection
– Diagnosed 11 years prior
– CD4 cell count of less than 200/μL (20 × 109/L)
– HIV viral load of higher than 750 000 copies/mL
despite ongoing antiretroviral therapy
• He has a history of many past opportunistic
infections
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Pneumocystis jiroveci pneumonia
Cryptococcal meningitis
Cytomegalovirus retinitis
Disseminated Mycobacterium avium complex
Care at the Close of Life: Evidence and Experience
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Mr C’s Story
• He also has had multiple other complications
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Rectal carcinoma
Scrotal carcinoma in situ
Peripheral neuropathy
Chronic wasting syndrome
• Treatment-related complications have included
– Thrombocytopenia after chemotherapy and radiation
for rectal carcinoma
– A ruptured globe after multiple intravitreal ganciclovir
implants for chronic cytomegalovirus retinitis
– Uveitis secondary to rifabutin
– Chronic renal insufficiency secondary to tenofovir
Care at the Close of Life: Evidence and Experience
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Mr C’s Recent Medications
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Didanosine
Ritonavir
Saquinavir
Efavirenz
– The above 4 medications were recently suspended
because of worsening nausea and anorexia and
concerns about possible lactic acidosis
• Levofloxacin
• Ethambutol
– Also recently suspended because of gastrointestinal
intolerance
Care at the Close of Life: Evidence and Experience
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Mr C’s Recent Medications
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Fluconazole
Trimethoprim-sulfamethoxazole
Valacyclovir
Azithromycin
Long-acting morphine sulfate
Dronabinol
Zolpidem
Sertraline
Famotidine
Filgrastim
Erythropoietin
Care at the Close of Life: Evidence and Experience
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Mr C’s Story
• Dr K (Mr C’s HIV physician) wonders whether
Mr C has consistently adhered to antiretroviral
therapy regimens
– Mr C has had a persistently elevated viral load
• Over the years, Mr C was admitted and
discharged from hospice programs several times
– He has had conflicting feelings about advance
directives concerning life-prolonging interventions
Care at the Close of Life: Evidence and Experience
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Challenges of HIV/AIDS as a Chronic Disease
• In developing countries, HIV/AIDS is more likely
to follow the grimly predictable, stereotypic, and
rapidly fatal course seen in the early phase of
the epidemic
– In the United States in the early 1980s, the median
time from AIDS diagnosis to death was often less
than 1 year
• Access limitations in developing countries
– Basic health care
– Antiretroviral therapy
Care at the Close of Life: Evidence and Experience
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Challenges of HIV/AIDS as a Chronic Disease
• AIDS has become a chronic disease in the
United States and other industrialized countries
– Its prevalence has increased, as people live longer
with it
– It is now a prolonged illness with exacerbations and
remissions
– There is a growing cumulative disease burden
– There are significant therapy-related toxic effects
– There are increasing medical and psychiatric
comorbidities
Care at the Close of Life: Evidence and Experience
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Challenges of HIV/AIDS as a Chronic Disease
• Its symptom burden
– Is comparable to other serious chronic illness such as
chronic heart, lung, and renal disease
– Requires palliative care
Care at the Close of Life: Evidence and Experience
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Challenges of HIV/AIDS as a Chronic Disease
• Still, AIDS ultimately remains a life-threatening
illness
– There have been 15 000 deaths per year since 1997
– It is a leading cause of death among young adults
aged 25-44 years, especially among African
Americans and Hispanics
– It requires end-of-life care
Care at the Close of Life: Evidence and Experience
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Challenges of HIV/AIDS as a Chronic Disease
• HIV/AIDS is both a chronic disease and a lifethreatening disease
– It is a false dichotomy to focus on either disease
management or symptom management
• Its treatment plan must integrate both
– Curative or disease-specific interventions
• Highly active antiretroviral therapy (HAART)
• Treatment of opportunistic infections
– Symptom palliation
Care at the Close of Life: Evidence and Experience
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Late-Stage HIV Disease
• Late-stage disease is defined as longstanding,
symptomatic HIV disease
• It is associated with
– Severe immunosuppression
– Significant cumulative morbidity
– Failure of or inability to tolerate antiretroviral therapy
Care at the Close of Life: Evidence and Experience
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Medical Challenges: Cumulative Disease Burden
• Life-prolonging treatment can create morbidities
– Decline in physical functioning
– Poorer quality of life
– Worse appearance
• Adverse effects of disease-specific therapy
– eg, nausea or vomiting, neuropathy, uveitis, renal
insufficiency, hyperamylasemia, lactic acidosis
• Hazards of longstanding HIV-associated
immunosuppression
– eg, cancer
Care at the Close of Life: Evidence and Experience
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Medical Challenges: Comorbid Illnesses
• Comorbid illnesses have a major impact on
morbidity and mortality in patients with HIV/AIDS
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Hepatitis B
Hepatitis C
Non–AIDS-defining cancers
Psychiatric disorders
Substance abuse–related sequelae
• Some comorbid illness can account for a burden
of mortality comparable to or greater than the
total mortality of AIDS itself
– Malignancy
– Cirrhosis or liver failure
Care at the Close of Life: Evidence and Experience
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Medical Challenges: Aging
• There is a growing prevalence of age-related
comorbidities
– Degenerative joint disease
– Osteoporosis
– Psychiatric disorders, especially mood and anxiety
disorders
– Cognitive decline
• HIV-related cognitive disorders
• Age-related cortical impairments
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Immunologic senescence
Age-associated increased cancer risk
Increasing prevalence of metabolic disorders
Increasing prevalence of cardiovascular disease
Care at the Close of Life: Evidence and Experience
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Medical Challenges: Aging
• Polypharmacy
– Common in elderly patients in general
– Has implications for HIV-related therapies
• Risk of increasing social isolation
– Common in elderly patients in general
– Is potentially compounded by the stigma and isolation
related to HIV/AIDS
• Impact of long-term survival on maintaining safer
sex behaviors
– Fatigue with respect to self-regulatory behavior
Care at the Close of Life: Evidence and Experience
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Medical Challenges: Pain and Other Symptoms
• High prevalence of pain and other symptoms
– Especially in the later stages
– May be underrecognized, undertreated, or both
Care at the Close of Life: Evidence and Experience
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Prevalence of Symptoms in Patients With AIDS
Symptom
Percentage Range
Fatigue or lack of energy
48-85
Weight loss
37-91
Pain
29-76
Anorexia
26-51
Anxiety
25-40
Insomnia
21-50
Cough
19-60
Nausea or vomiting
17-43
Dyspnea or respiratory symptoms
15-48
Depression or sadness
15-40
Diarrhea
11-32
Constipation
10-29
Care at the Close of Life: Evidence and Experience
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Medical Challenges: Symptoms
• Symptom management
– May improve adherence to HIV-specific therapies
– Has been demonstrated effective in limited research
• Patient self-care symptom management
strategies with documented utility in AIDS
include
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Exercise
Meditation
Prayer
Complementary and integrative practices
Care at the Close of Life: Evidence and Experience
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Medical Challenges: Symptoms
• The best palliation may be
– Disease-specific therapy
• eg, fluconazole for cryptococcal meningitis
– Symptom-specific therapy
• eg, antiemetics for medication-induced nausea
Care at the Close of Life: Evidence and Experience
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Medical Challenges: Psychiatric Symptoms
• Psychotic, anxiety, or mood disorders can cause
significant morbidity
• They may also shorten longevity
– They may affect patients’ motivation and capacity to
adhere to medical treatment
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
Medical Challenges: Psychiatric Symptoms
• Cognitive disorders in late-stage HIV disease
– Confound the clinical picture
– Limit information processing and decision making
• Useful interventions include
– Psychiatrists and other mental health professionals
– Support groups
• Randomized controlled trials demonstrate less depression
and feelings of meaninglessness and better spiritual wellbeing
Care at the Close of Life: Evidence and Experience
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Medical Challenges: Combining Disease-Specific
and Palliative Approaches
• AIDS care cannot readily be dichotomized into
curative vs palliative approaches
• However, there is a disconnect between the
paradigms of HIV care and palliative care
– At the XIV International Conference on AIDS in 2002,
less than 1% of nearly 6000 abstracts focused
primarily on palliative care–related topics
– At the 14th Annual Assembly of the American
Academy of Hospice and Palliative Medicine in 2002,
only 2% of the 105 abstracts dealt primarily with
HIV/AIDS
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
Medical Challenges: Combining Disease-Specific
and Palliative Approaches
• Comprehensive HIV/AIDS care must include
scrupulous management of HAART medications,
but also of symptoms and psychiatric disease
• The clinician must be aware of the potential for
drug interactions between palliative and HIV
medications
– eg, certain opioids, antidepressants, anticonvulsants,
and benzodiazepines interact with the protease
inhibitors, nonnucleoside reverse transcriptase
inhibitors, and rifamycins
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
Medical Challenges: Combining Disease-Specific
and Palliative Approaches
• Some medications that are not routinely used in
HIV/AIDS treatment may be needed for palliation
– eg, short-term use of corticosteroids for anorexia,
malaise, fevers, fatigue, or nausea is not deleterious
and may improve quality of life for patients with
late-stage disease
• Clinicians must remain aware of ongoing
inequalities in access and integration of care for
patients with AIDS
Care at the Close of Life: Evidence and Experience
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Prognostic Challenges: Clinical Markers
• Pre-HAART mortality was readily and uniformly
predicted by
– Occurrence of specific opportunistic infections
– Surrogate markers
• CD4 T-lymphocyte cell counts
• HIV viral loads
Care at the Close of Life: Evidence and Experience
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Prognostic Challenges: Clinical Markers
• Now, prognostic markers are much less reliable
in late-stage disease
– Any of the traditional prognostic markers may be
overridden by the potential impact of HAART
– US National Hospice Organization guidelines no
longer predict 6-month mortality accurately
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
Prognostic Challenges: Clinical Markers
• Better predictors of prognosis in advanced HIV
– Functional deficits
• Impaired activities of daily living
• Cognitive impairments on mental status examination
– Existence of other life-threatening conditions
• Cancer
• End-organ failure
• New prospective studies are needed to develop
prognostic variables for late-stage HIV disease
in the HAART era
Care at the Close of Life: Evidence and Experience
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Prognostic Challenges: Discontinuation of HAART
• There are detailed guidelines for the initiation of
HAART
• But there are no guidelines to guide the
discontinuation of HAART in the setting of
treatment failure
• The clinician must weigh the potential benefits
and risks of its discontinuation
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
Potential Benefits of HAART in Late-Stage HIV
• Selection for less fit virus (ie, less pathogenic
than wild type virus), even in the presence of
elevated viral loads
• Protection against HIV encephalopathy or
dementia
• Relief or easing of symptoms possibly associated
with high viral loads (eg, constitutional symptoms)
• Continued therapeutic effect, albeit attenuated
• Psychological and emotional benefits of
continued disease-combating therapy
Care at the Close of Life: Evidence and Experience
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Potential Risks of HAART in Late-Stage HIV
• Cumulative and multiple drug toxic effects may
occur in the setting of therapeutic futility
• There may be diminished quality of life from the
demands of the treatment regimen
• There may be therapeutic confusion (ie, use of
future-directed, disease-modifying therapy in a
dying patient)
Care at the Close of Life: Evidence and Experience
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Potential Risks of HAART in Late-Stage HIV
• Distraction from end-of-life and advance care
planning issues, with a narrow focus on
medication adherence and monitoring
• Evidence is lacking for some of the potential
benefits mentioned although they are commonly
considered in clinical decision making
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
Advance Care Planning
• Physician discussion of advance directives and
life-limiting interventions is less common with
HIV/AIDS patients
• There are multiple barriers to advance care
planning in HIV/AIDS
– Physicians’ discomfort with discussing death
– Physicians’ reluctance to undermine hope
– Availability of HAART
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
Advance Care Planning
• The clinician must address the patient’s concern
that palliative care is somehow less than
standard care
– AIDS is concentrated in vulnerable populations
• African Americans have been noted to be less likely to
consider withdrawal or cessation of life-prolonging measures
than certain other racial or ethnic groups
– There is a persistent societal stigma associated with
AIDS
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
Shift Toward Palliation
• The shift toward palliation is an ongoing iterative
process in which the potential benefits, risks, and
burdens of particular therapies are repeatedly
assessed
– The range of disease-specific treatments narrows
• eg, might continue PCP prophylaxis but not HAART
– The focus of treatment may become primarily palliative
• There is no rigid template for this process
– It requires a specific, individualized treatment plan
– It must be consistent with the patient’s expressed
goals of care
– The goals may evolve over time
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
The “Chronic” Caregiver
• Caregiver emotions have intensified in the
chronic disease era
– Feelings of anger, dread, relief, guilt, isolation, and
feelings of loss of control
– Burdens of exhaustion, anxiety, and uncertainty
• Physicians should proactively address these
issues
– Normalize the need for caregiver help
– Refer to support groups
– Inform caregivers about respite programs that
hospice services may provide
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
The Physician’s Role
• Clinician frustration in advanced HIV in the
HAART era includes
– Being aware of what the therapy can provide and
then being confronted with the evidence of its failure
• The possibility of greater hope is darkened by
disappointment, regret, guilt, and second-guessing
– More of the responsibility for the disease’s outcome is
placed in the hands of the patient and the physician
• Patients and families may blame physicians for the disease
outcome
• Physicians may blame patients for non-adherence
• Physicians may blame themselves for failed treatments
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
The Physician’s Role
• There is an ongoing, even deepening role for the
physician with patients dying of HIV/AIDS
• The experience can be moving and life-changing
for physicians as well
– Many physician-authors have described personal
pain, transcendence, and growth
– “If you listen carefully to your patients, they will tell
you not only what is wrong with them, but also what is
wrong with you.” —Walker Percy in Love in the Ruins
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
The End of the Story
• Mr C developed worsened mobility
– Neuropathy and loss of vision progressed
– He began to rely on a motorized scooter to move
around outside his home
• Ms D (Mr C’s aunt, his primary caregiver) and Dr
K both noted a progressive cognitive
deterioration during the next several months
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
The End of the Story
• Unable to eat or drink at home, Mr C was
admitted to the hospital for comfort care
• Two days later (11 years after his diagnosis of
HIV), Mr C died from hepatic and respiratory
failure
– Likely secondary to aspergillosis and toxic effects
from his therapeutic regimen
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
This Education Guide slide set
has been created as a part of
Care at the Close of Life: Evidence and Experience
Michael W. Rabow, MD
University of California, San Francisco
Education Guides Editor
Stephen J. McPhee, MD; Margaret A. Winker, MD; Michael W. Rabow, MD; Steven Z. Pantilat, MD; Amy J. Markowitz, JD
Care at the Close of Life: Evidence and Experience Editors
Care at the Close of Life: Evidence and Experience
Copyright © American Medical Association. All rights reserved. | JAMA | The McGraw-Hill Companies, Inc.
HIV/AIDS
Selwyn PA, Forstein M. Overcoming the false
dichotomy of curative vs palliative care for latestage HIV/AIDS. In: McPhee SJ, Winker MA,
Rabow MW, Pantilat SZ, Markowitz AJ, eds. Care
at the Close of Life: Evidence and Experience.
New York, NY: McGraw-Hill; 2010:173-185.
http://www.jamaevidence.com/content/6604568
Care at the Close of Life: Evidence and Experience
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