Transcript Ongoing Debates in Recurrent Ovarian Cancer A Case–Based

Improving Quality of Life in the
Treatment-Experienced Patient With HIV
Management of Treatment-Related Toxicities
Valery Hughes, RN, MS, C-FNP
Research Nurse Practitioner/Sub-investigator
Weill Medical College of Cornell University
Division of Infectious Diseases
New York, NY
HIV Treatment
The Good and the Bad
• Impact of combination antiretrovirals: good
• Treatment of the newly diagnosed: pretty good
• Choices for experienced patients: maybe not
so good, certainly more complicated
• The purpose of this talk will be to review some
of these issues and discuss ways to address
them
Case Discussion #1
FYG Darunavir, C202
• Diagnosed in 1995, presented with PCP
• History of cryptococcal meningitis, seizures,
wasting, thrush, zoster
• CD4 nadir ~21 cells/mm3 in 2001
• 4 class exposure (had been in T1249/T20
study in early 2001)
• History of:
– Immune reconstitution
– Abacavir hypersensitivity reaction
Case Discussion #1
FYG Darunavir, C202
• Social
–
–
–
–
Employed full time as RN
Lives with daughter in Manhattan apartment
Close, supportive family
Good understanding of HIV life cycle and need for
strict adherence
Case Discussion #1
FYG Darunavir, C202
• Presented for screening in December 2003
– Medications at that time: lopinavir-based regimen
– Baseline HIV RNA 1.7 million copies/mL
Case Discussion #1
FYG Darunavir, C202
• Started DRV-based regimen including ZDV
and ENF on 2/17/04
• Week 2 HIV RNA 14,653 copies/mL
• Hemoglobin: 6.1 g/dL by week 2
– Grade 4 anemia
• Reported fatigue
• Epoetin alfa 40,000 U/mL 1 mL weekly started
– Hgb increased and stabilized at just over 11
Case Discussion #1
FYG Darunavir, C202
HIV-RNA
1800000
Hgb
16
1,700,000
1600000
14.2
14
1400000
12
1200000
11.5
10
1000000
8
800000
6.1
6
600000
400000
4
200000
2
14,653
0
baseline
wk 2
292
wk 8
0
baseline
wk 2
wk 8
Anemia
• Lower than normal levels of Hgb
– Normal Hgb
• Female: 12 to 16 g/dL
• Males: 14 to 18 g/dL
• Causes of anemia
– Decreased RBC production
• infection, medication (AZT-containing), HIV disease itself
– Increased RBC destruction/loss (i.e., hemolysis)
• Blood loss (bleeding ulcer, menstrual cycle)
– Ineffective RBC production
• Nutritional deficiency: vitamin B12, folic acid
Volberding PA, et al. Clin Infect Dis. 2004 May 15;38(10):1454-1463.
Common Symptoms of Anemia
•
•
•
•
•
•
•
•
•
•
•
•
Fatigue
Weakness
Shortness of breath
Dizziness or fainting
Pale skin, including decreased pinkness of the lips, gums, lining on
the eyelids, nail beds and palms
Rapid heart beat (tachycardia)
Feeling cold
Sadness or depression
Decreased sexual function
Difficulty sleeping
Decreased appetite
Impaired cognitive function
Volberding PA, et al. Clin Infect Dis. 2004 May 15;38(10):1454-1463.
Signs and Symptoms of Anemia
CNS
•
•
•
•
Immune System
Debilitating fatigue
Dizziness, vertigo
Depression, sadness
Impaired cognitive function
Gastrointestinal System
• Anorexia
• Nausea
Vascular System
• Low skin temperature
• Pallor of skin, mucous
membranes, and conjunctivae
• Impaired T-cell and
macrophage function
Cardiorespiratory System
• Exertional dyspnea
• Tachycardia, palpitations
• Cardiac enlargement,
hypertrophy
• Increased pulse pressure,
systolic ejection murmur
• Risk of life-threatening cardiac
failure
Genital Tract
• Menstrual problems
• Loss of libido
Volberding PA, et al. Clin Infect Dis. 2004 May 15;38(10):1454-1463.
WHO Criteria for Assessment of
Therapy-Induced Toxicity: Anemia
Severity of Anemia
Hgb Range
Grade 0
≥ 11.0 g/dL
Grade 1
9.5-10.9 g/dL
Grade 2
8.0-9.4 g/dL
Grade 3
6.5-7.9 g/dL
Grade 4
< 6.5 g/dL
WHO = World Health Organization
Risk Factors Currently Associated With
Anemia in HIV Infection
•
•
•
•
•
•
•
•
•
•
•
History of clinical AIDS
CD4 cell count of <200 cells/µL
Plasma viral load
Female Gender
African-American race
Zidovudine (AZT) use
Increasing age
Lower body mass index (BMI)
History of bacterial pneumonia
Oral candidiasis
History of fever
Volberding PA, et al. Clin Infect Dis. 2004 May 15;38(10):1454-1463.
Drugs That Commonly Cause Anemia
in HIV-Infected Patients
•
Antiretrovirals
– Zalcitabine
– AZT-containing therapy (Retrovir®,Combivir®, Trizivir®)
•
Antiviral Agents
– Flucytosine
– Amphotericin
•
Anti-Pneumocystis Carinii (Pneumocystis jiroveci) Agents
–
–
–
–
•
Sulfonamides
Trimethoprim
Pyrimethamine
Pentamidine
Antineoplastic Agents
– Cyclophosphamide, doxorubicin, methotrexate, paclitaxel, vinblastine
•
Immune Response Modifiers
– IFN-α
Volberding PA, et al. Clin Infect Dis. 2004 May 15;38(10):1454-1463.
Prevalence of Anemia* by Race
39%
40%
35%
31%
30%
25%
19%
20%
12%
15%
African American
Caucasian
10%
5%
0%
Women
Men
*Anemia was defined as <12 g/dL for women and < 13 g/dL for men
Levine AM, et al. J Acquir Immune Defic Syndr. 2001 Jan 1;26(1):28-35.
Semba RD, et al. Clin Infect Dis. 2002 Jan 15;34(2):260-266.
Prevalence of Anemia* During HAART
70%
64%
60%
47%
50%
40%
54%
52%
46%
35%
No anemia
Mild anemia
Severe anemia
30%
20%
10%
1.5%
1.2%
0.6%
0%
Start
6 Months
12 Months
* No anemia: > 12 g/dL women; >14 g/dL men
Mild anemia: 8-12 g/dL women; 8-14 g/dL men
Severe anemia: <8 g/dL for both women and men
Levine AM, et al. J Acquir Immune Defic Syndr. 2001 Jan 1;26(1):28-35.
Semba RD, et al. Clin Infect Dis. 2002 Jan 15;34(2):260-266.
Anemia
Linear Analog Scale Assessment
Questions about how you felt during the past week are listed below. Place a
vertical mark somewhere between the two extremes to reflect how you feel.
1. How would you rate your energy level during the past week?
As low as
could be
As high as
could be
2. How would you rate your ability to do your daily activities over the past week?
As low as
could be
As high as
could be
3. How would you rate your overall quality of life during the past week?
As low as
could be
As high as
could be
Volberding PA, et al. Clin Infect Dis. 2004 May 15;38(10):1454-1463.
Anemia
Patient Self-Assessment
For each statement, which answer best describes how you're feeling?
1. I lack the strength to do the everyday things I used to do.
All the time
Most of the time
Occasionally
2. I feel tired and weak more quickly than usual.
All the time
Most of the time
Occasionally
3. I feel dizzy after climbing stairs or walking short distances.
All the time
Most of the time
Occasionally
4. I am short-of-breath after simple tasks like cooking meals or getting
dressed.
All the time
Most of the time
Occasionally
5. I find it difficult to concentrate during activities like reading.
All the time
Most of the time
Occasionally
Treatment of HIV and
Treatment-related Anemia
• Transfusion
• Epoetin alfa (PROCRIT®)
Volberding PA, et al. Clin Infect Dis. 2004 May 15;38(10):1454-1463.
Treatment of HIV and
Treatment-related Anemia
• Epoetin alfa
– 40,000 Units QW or 10,000 Units TIW
• Allow at least 4 weeks to assess dose response
– ± Iron supplementation as indicated*
– If no response at 4 weeks
• Increase from 10,000 Units TIW to 20,000 Units TIW
• Increase from 40,000 Units QW to 60,000 Units QW
– Optimal Hgb: ≥13 g/dL men, ≥12 g/dL women
– Maintain Hgb by titrating dose or increasing dosing interval
*Ferritin <100ng/mL, transferrin saturation <20%
TIW = three times weekly; QW = once weekly
Volberding PA, et al. Clin Infect Dis. 2004 May 15;38(10):1454-1463.
Case Discussion #1
FYG Darunavir, C202
• Enfuvirtide injection site reactions
– Increased risks include decreased overall
subcutaneous fat
– No hard data regarding traditional injections vs. the
Biojector®2000
– Anecdotes are about 70/30 in favor of the
Biojector®2000 in my practice
– FYG used traditional injections and had the classic
reactions worse on thighs than on abdomen
Injection Site Reactions
•
•
•
•
Ice before
Ice after
Heat after
Pressure after
• Results?
Adherence
• Multiple factors influence adherence
– Readiness to start or continue treatment
• This needs to be evaluated fully in the context of the
patient’s life: a full social history is important
– Belief in treatment efficacy
– Fear of side effects
– Psychiatric disorders
Predictors of Good Adherence
• Availability of emotional and practical life
supports
• Ability to fit the medications into daily routine
• Understanding that poor adherence leads to
resistance
• Recognition that taking all medication doses is
important
• Feeling comfortable taking medications in
front of people
Willard S. J Assoc Nurses AIDS Care. 2006 Mar-Apr;17(2):16-26.
Predictors of Poor Adherence
•
•
•
•
•
Poor clinician-patient relationship
Active drug and alcohol use
Active mental illness, particularly depression
Lack of patient education
Inability of patients to identify their
medications
• Lack of reliable access
• Domestic violence and discrimination
• Medication side effects
Willard S. J Assoc Nurses AIDS Care. 2006 Mar-Apr;17(2):16-26.
SIDE EFFECTS
Case Discussion #2
TLR
• Found to be positive after becoming septic
post-hysterectomy
• Single mother, disclosure issues, very angry
about how she was infected
• Started naïve study (A5095, in fact) and
quickly became undetectable
• Ultimately failed 3 regimens: why?
Case Discussion #2
TLR
• Disclosure issues
– She never told her mother or her children, and did
not want to be seen “taking pills”
• Often missed evening and weekend doses
• Anger issues
– Had only had sex with one man, and found later
that he knew he was HIV positive
– Would not discuss this with social worker, MD,
psychiatrist, sister, anyone; but, anger and grief
often erupted during visits about adherence
Case Discussion #2
TLR
• What did we do?
– Presented a united message
• We all said the same thing: “take all your doses or choose
to stay off treatment”
– Supported her choice to stay off medications
– Encouraged her to disclose to her family to help
get family support
– Restarted regimen when she felt she could be
adherent
Lipodystrophy
• No generally accepted case definition of
syndrome(s)
• Initial reports suggested clustering of:
–
–
–
–
Central fat accumulation
Lipoatrophy
Dyslipidemia
Insulin resistance/type 2 diabetes mellitus
• One syndrome or several?
Lipodystrophy as a Metabolic Syndrome
• Compared with age and BMI matched controls from
the Framingham Offspring Study, HIV+ patients with
lipodystrophy had:
– Higher diastolic blood pressure
– Elevated triglycerides, total cholesterol (not LDL)
– Lower HDL
– Elevated tPA and PAI-1 levels (markers of impaired
fibrinolysis)
Hadigan C, et al. Clin Infect Dis. 2001 Jan;32(1):130-139.
Hadigan C, et al. J Clin Endocrinol Metab. 2001 Feb;86(2):939-943.
Case Discussion #3
DWC Darunavir, C202
• 36-year-old African American found to be
HIV+ in 1993
–
–
–
–
Cryptococcal meningitis in 1994
No other OIs
Peripheral neuropathy
Triple-class exposure starting in 1993
• Type 2 Diabetes, 2002
• Hypertension, 2003
• Hyperlipidemia, 2003
Case Discussion #3
DWC Darunavir, C202
• Presented with moderate lipoaccumulation:
– In dorsocervical area
– +Gynecomastia with band of fatty tissue extending bilaterally
and symmetrically laterally into the axilla*
• Otherwise very muscular
• Very aggressive about managing his body shape as
much as possible
– 5 x per week: 30 min cardio and 45 min weight training
*As described by Palella FJ Jr, et al. JAMA. 2006 Aug 16;296(7):766-768.
Palella FJ Jr, et al. JAMA. 2006 Aug 16;296(7):766-768.
Psychological Impact of
Morphologic Changes
• Conflicting data on whether there is a negative
impact on QOL or association with depression
– Poor body image reported in men and women
– Decreased social contact, self-esteem, sexual
function in majority of subjects in one study
– Twice as likely to feel recognizable as HIV+ person
Steel, AIDS Pt Care STDs 2006; Huang, AIDS Res 2006;Goetzenich, IAS 2000; Falutz, Forum Nutr 2003;
Oette AIDS Pt Care STDs 2002; Corless AIDS Pt Care STDs 2005; Guaraldi G HIV Clin Trials 2003;
Collins AIDS Behav 2006; Ammassari, JAIDS 2002
Valantin MA, et al. AIDS 2003 Nov 21;17(17):2471-2477.
Risk Factors for Lipoatrophy
•
•
•
•
•
•
•
Older age
Duration of HIV
Lower pre-treatment BMI
Hypertriglyceridemia
Low nadir CD4
TNF- promoter polymorphisms
Use of NRTIs, especially d4T
– PIs may be synergistic
Lichtenstein KA, et al. AIDS. 2001 Jul 27;15(11):1389-1398. McComsey G, et al.
AIDS Read. 2003 Nov;13(11):539-542, 559. Nolan D, et al. AIDS. 2003 Jan 3;17(1):121-123.
Mallal SA, et al. AIDS. 2000 Jul 7;14(10):1309-1316. Dube MP, et al. AIDS 2005 Nov 4;19(16):1807-1818.
Lipodystrophy
Summary
• Morphologic complications of HIV/antiretroviral therapy
are more than cosmetic concerns
– Associated metabolic syndrome with insulin resistance,
dyslipidemia
– Psychological impact
• Accelerated atherosclerosis is a long-term concern
• Metabolic factors appear to be associated with hepatic
steatosis
– Associated with fibrosis and decreased treatment response in
the setting of HCV coinfection
• Promising therapeutic approaches are under study
• Until then, patient teaching regarding diet and exercise
are still valuable
Gastrointestinal – Diarrhea
• Associated with many meds
– If so, can be treatment limiting
• May have an indeterminate cause
• Problem in quality of life
Case Discussion #4
JOG
•
•
•
•
•
•
39-year-old white male
HIV+ 1992
Presented with triple-class failure
History of adherence issues
HIV RNA 248,712 copies/mL (5.39 log10)
CD4 299 cells/mm3
Case Discussion #4
JOG
• Started new regimen 7/30/03 on RESIST-1,
using 500 mg TPV and 200 mg RTV BID
• Developed loose stools 4-5 times a day
almost immediately
• Loose stools attributed to PI regimen because
of temporal relationship
Case Discussion #4
JOG
• Started Imodium with improvement
– Other options might include fiber such as psyllium
husks or other OTC remedies if stool was watery
– If CD4 count was lower, it would warrant work up
including stool studies and GI consult
• Self-discontinued all ARVs despite excellent
virologic and immunologic response
Summary
• In a perfect world, ARVs would be an invisible
patch placed annually and with no side effects
– We are not there yet
• In a perfect world, all patients would be ready
to start treatment, have great support,
unlimited access and fabulous families
• But think how far we have come in 25 years
• Nursing interventions continue to be key in
maintaining the quality of life for people living
with HIV
Thanks to:
Our research subjects,
particularly those discussed
today!
Cornell HIV Clinical Trials Unit
Trip Gulick
Marshall Glesby
Joanne Grenade
Glenn Sturge
Tim Wilkin
Kristen Marks
Kirsis Ham
Todd Stroberg
Christina Megill
Natacha Joseph
Marisol Valentin
Eduardo Baez
Luis Lopez-Detres