challenging cases in hiv implications of anemia david h. henry, md clinical professor of medicine...
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![Page 1: Challenging Cases in HIV Implications of Anemia David H. Henry, MD Clinical Professor of Medicine Pennsylvania Hospital Joan Karnell Cancer Center Philadelphia,](https://reader036.vdocuments.net/reader036/viewer/2022062515/56649c9e5503460f9495e733/html5/thumbnails/1.jpg)
Challenging Cases in HIVImplications of Anemia
David H. Henry, MDClinical Professor of Medicine
Pennsylvania Hospital Joan Karnell Cancer Center
Philadelphia, PA
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Case Discussion #1
• A 37-year-old female, HIV positive for five years.• CD4 350 cells/mm3, viral load undetectable (<50 copies/mL)• Current Therapy: Combivir® + Sustiva®
• She has a two-month history of weakness• Denies GI/GU bleeding• Menstrual cycle normal• Physical examination is unremarkable • Stool Hemoccult negative
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Case Discussion #1
• Lab results– Hemoglobin 7.6 g/dL
– MCV 92
– RDW 10%
– WBC 6.8
– Platelets 440
– Peripheral smear, NCNC RBC, and reticulocytes 0.2%
– Creatinine 0.9 mg/dL
– Ferritin 440 ng/mL
– B12 340 pg/mL
– Folate 10 nmol/L
– EPO level 600 mU/mL
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Case Discussion #1
• Clinical evaluation– Underproductive anemia mechanism with normal MCV
– Normal creatinine, B12, folate, and ferritin
– Reticulocytes are very low consistent with bone marrow, severely depressed
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Anemia Work-up
Reticulocyte count Underproductive (<5%) Overdestructive (>10%)
………………………………………..
110 ….. B12, folate deficiency, MDS
MCV 90 ….. ACD, CRF, drugs……….
70 ….. Fe deficiency, thalassemia…
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Case Discussion #1
• What is your diagnosis of this patient? Anemia of chronic disease secondary to HIV Treatment-related anemia Anemia due to blood loss (GI/GU bleeding)
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Case Discussion #1
• What is your diagnosis of this patient?– AZT-related anemia
• AZT-related anemia comes in two forms:─ MCV normal
» Severe anemia and severe EPO elevation (bone marrow failure)
─ MCV increased
» Mild anemia and mild EPO elevation
• AZT-related anemia of profound type─ Frequently happens in patients who have been on AZT
for some time, as in this patient
─ Patients have normal MCV
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Case Discussion #1
• What therapy would you consider for this patient? Discontinuation of AZT therapy Begin EPO therapy (epoetin alfa) Change HIV therapy to non-AZT-containing regimen Discontinue AZT-therapy and begin EPO therapy Change HIV therapy and begin EPO therapy
• Recommendation– Discontinuation of AZT usually results in complete
recovery– Not responsive to EPO therapy (EPO > 500 mU/mL)
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Case Discussion #2
• A 47-year-old male, IV drug user
• Complaining of weakness, low-grade fevers, and night sweats
• Denies GI or GU bleeding
• History of shingles, but no other opportunistic infections
• Physical examination reveals temperature 99.6º F
• Few enlarged cervical axillary lymph nodes and positive thrush
• Stool Hemoccult negative
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Case Discussion #2
• Lab results:– Hemoglobin 9.1 g/dL
– WBC 3.7
– Platelets 560
– Reticulocyte 0.9%
– MCV 89
– Creatinine 1.2 mg/dL
– Chest x-ray negative
– Urinalysis and urine culture unremarkable
– Blood culture sent, the patient agrees to HIV testing, which is positive
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Case Discussion #2
• Baseline labs:– CD4 80 cells/mm3
– Viral load over 100,000 copies/mL
– Ferritin 620 ng/mL
– B12 400 pg/mL
– Folate 9 nmol/L
– EPO level 30 mU/mL
• Patient agrees to start HAART and HIV resistance testing is sent– Four weeks later, blood cultures return positive for MAI
(Mycobacterium avium-intracellulare)
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Case Discussion #2
• Clinical evaluation
– Underproductive anemia with normal MCV
– Folate, B12, ferritin, and creatinine normal
– EPO level inadequate for a degree of anemia at 30 mU/mL
– No HIV medications started as of yet
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Case Discussion #2
• What is your diagnosis of this patient? Anemia of chronic disease secondary to HIV Anemia associated with opportunistic bone marrow
infection Anemia due to blood loss (GI/GU bleeding) Anemia due to nutritional deficiency
• Diagnosis– Anemia of chronic disease secondary to HIV,
untreated, and development of MAI systemic infection
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Case Discussion #2
• What therapy would you consider for this patient? Initiation of HAART MAI therapy Consideration of EPO therapy All of the above
• Recommendation– Initiation of HAART
– MAI therapy
– Consideration of EPO therapy
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Case Discussion #3
• A 36-year-old male, HIV positive for 10 years
• History of PCP at diagnosis
• HAART second-line therapy: Truvada® + Reyataz® + Norvir®
• CD4 275 cells/mm3
• Viral load 800 copies/mL
• He is complaining of rectal irritation and fatigue for two months. Denies GI or GU bleeding
• On physical exam, no lymphadenopathy and no hepatosplenomegaly
• There is a 2-cm perianal mass with positive stool Hemoccult– Biopsy of anal mass is positive for anal squamous cell carcinoma
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Case Discussion #3
• Lab results– Hemoglobin 8 g/dL
– MCV 70
– RDW 18%
– WBC 4.7
– Platelets 120
– Reticulocytes 0.9%
– EPO level 300 mU/mL
– Ferritin 9 ng/mL
– B12 400 pg/mL
– Folate 7 nmol/L
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Case Discussion #3
• What is your diagnosis of this patient? Anemia of chronic disease secondary to HIV Treatment-related anemia Anemia associated with iron deficiency due to blood
loss (GI/GU bleeding)
Diagnosis– The patient has iron deficiency anemia due to occult
GI bleeding from his anal carcinoma
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Case Discussion #3
• What therapy would you consider for this patient?
• Recommendation– Treatment would consist of p.o./IV iron (some question
about oral iron absorption in patients with inflammation)
– The patient would also require chemoradiation therapy due to his anal cancer
– Initiation of EPO therapy
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Prevalence and Implications of Anemia in the Patient with HIV
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Distribution of Hb in Anemic HIV Patients
Nadler JP et al. 5th IWADRL in HIV, Paris 2003
0%
10%
20%
30%
40%
50%
60%
70%
8.0-8.9 9.0-9.9 10.0-10.9 11.0-11.9 12.0-12.5
Hemoglobin level (g/dL)
Pat
ient
s (
%)
n = 6n = 12
n = 22
n = 36
n = 154
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Distribution of Hb by Gender
Nadler JP et al. 5th IWADRL in HIV, Paris 2003
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Prevalence of Anemia* by Race/Gender
Levine AM et al., J Acquir Immune Defic Syndr 2001:26:28-35Semba R et al., Clin Infect Dis 2002;34:260-266
0%
5%
10%
15%
20%
25%
30%
35%
40%
Women Men
African American
Caucasian
39%
19%
31%
12%
*Anemia was defined as <12 g/dL for women and < 13 g/dL for men
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Baseline Hb by CD4+ Strata
Nadler JP et al. 5th IWADRL in HIV, Paris 2003
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Baseline Hb by VL Strata
Nadler JP et al. 5th IWADRL in HIV, Paris 2003
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Prevalence of Anemia According to Treatment Regimen
Nadler JP et al. 5th IWADRL in HIV, Paris 2003
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Prevalence of Anemia* During HAART
Levine AM et al., J Acquir Immune Defic Syndr 2001:26:28-35Semba R et al., Clin Infect Dis 2002;34:260-266
0%
10%
20%
30%
40%
50%
60%
70%
Start 6 Months 12 Months
No anemia
Mild anemia
Severe anemia
64%
47%54%
0.6%
35%
46%
52%
1.2%1.5%
* 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
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Creagh T, et al. IAS 2001; Poster 1049
Association of Anemia and HIV Disease Progression in Patients Receiving HAART
*Case definition = patients with 2 Hb levels < 11 g/dL; 21% met the case definition†P < .0001‡P = .001
0
1
2
3
4
5
6
7
8
9
Cases* Controls Female cases
Controls Male cases
Controls
Ove
rall
odds
rat
io f
or
HIV
pro
gres
sion
†
‡
(N = 501)
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Drugs that Commonly Cause Anemia in HIV-Infected Patients
• Antiretrovirals– Zalcitabine– AZT-containing therapy (Retrovir®,Combivir®, Trizivir®)
• Antifungal Agents– Flucytosine– Amphotericin
• Anti-Pneumocystis Carinii Agents– Sulfonamides– Trimethoprim– Pyrimethamine– Pentamidine
• Antineoplastic Agents– Cyclophosphamide, doxorubicin, methotrexate, paclitaxel, vinblastine
• Immune Response Modifiers– IFN-α
Volberding P et al., Clinical Infectious Diseases 2004;38:1454-1463
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Hb as a Prognostic Factor for AIDS-Defining Illness (ADI)
• Incidence rate ratio (IRR) events/100 person-years– Hb < 10 g/dL 8.62 (95% CI:5.52, 13.3)
– Hb 10-11 g/dL 7.31 (95% CI:4.52, 11.7)
– Hb 11-12 g/dL 3.93 (95% CI:2.44, 6.35)
– Hb > 12 g/dL Reference group
Moore R et al. CROI 2004, Abstract K5
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Progression to Death for Patients According to Baseline Hb in EuroSIDA: Multivariate Analysis
Mocroft A, et al. AIDS. 1999;13:943-950
Months after recruitment
100
0 6 12 18 24 30 36
90
80
70
60
50
40
Pro
port
ion
aliv
e (%
)
P < .001
Normal (n = 2716)Hb >14 g/dL for men
and >12 g/dL for women
Mild (n = 3917)Hb 8-14 g/dL for men
and 8-12 g/dL for women
Severe (n = 92)Hb <8 g/dL for
men and women
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Recovery From Anemia Is Associated With Improved Survival (N = 3203)
Sullivan PS, et al. Blood. 1998;91:301-308
0
10
20
30
40
50
60
70
Recovery
No recovery
0-49
Med
ian
surv
ival
(m
onth
s)
CD4 count (cells/mL)
50-99 100-149 150-199 ≥200
Risk ratio (99% CI)
0.39(0.30-0.50)
0.43(0.32-0.59)
0.37(0.24-0.57)
0.27(0.17-0.45)
0.39(0.32-0.49)
P = .0001 for all CD4 categories (log rank)
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Progression of Hb During HAART
-2
-1.5
-1
-0.5
0
0.5
1
1.5
2 N=24 treatment-naïve, HIV-infected patients
Time on HAART (months)
0 3 6 9 12 15 18 21 24
Cha
nge
Fro
m B
asel
ine
Viral load( x log10RNA copies/mL)
Hb( x g/dL)
CD4 cell count( x 102 cells/µL)
Servais J, et al. JAIDS. 2001;28:221-225
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Association Between Anemia Treatments and Death Rates
Death Rate: Cox Proportional Hazards Model
Treatment RH P value
All Patients(n = 2348)
Epoetin alfa 0.57 .002
Transfusion 1.32 .003
Patients with Anemia(n = 498)
Epoetin alfa 0.68 .045
Transfusion 1.50 .002
Moore R. JAIDS. 1998;19:29
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Treatment of HIV and Treatment-related Anemia
• Epoetin alfa – Initiate Treatment
– Symptomatic vs asymptomatic
– Hb < 11 g/dL
– EPO < 500 mU/ml
– 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 Hb: ≥13 g/dL men, ≥12 g/dL women– Maintain Hb by titrating dose or increasing dosing interval
*Ferritin <100ng/mL, transferrin saturation <20%
Volberding P et al., Clinical Infectious Diseases 2004;38:1454-1463
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Treatment of HIV and Treatment-related Anemia
• Anemia is a not uncommon complication in HIV– Treatment-related toxicity (AZT-based therapy)
– HIV disease
– Opportunistic bone marrow infections
– Nutritional deficiencies
– Vitamin B12, iron or folate deficiencies
– Blood loss
• Symptoms of anemia can significantly impact a patient’s QOL and physical functioning (fatigue, sleeplessness, cognitive function)
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Treatment of HIV and Treatment-related Anemia
• Anemia risk factors– Female
– African American
– AZT-based therapy
– High HIV-RNA levels
– Low CD4 counts
• Treatment of anemia – Symptomatic, Hb < 11 g/dL, EPO < 500 mU/mL
– Epoetin alfa (40,000 Units QW)
– RBC Transfusions