Challenging Cases in HIV Implications of Anemia

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Challenging Cases in HIVImplications of Anemia

• David H. Henry, MD
• Clinical 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 (lt50
  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 (lt5) Overdestructive
  (gt10)
• ..
• 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 gt 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
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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
20012628-35 Semba R et al., Clin Infect Dis
200234260-266
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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
20012628-35 Semba R et al., Clin Infect Dis
200234260-266
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Association of Anemia and HIV Disease Progression
in Patients Receiving HAART
Case definition patients with 2 Hb levels lt 11
g/dL 21 met the case definition P lt .0001 P
.001
Creagh T, et al. IAS 2001 Poster 1049
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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-a

Volberding P et al., Clinical Infectious Diseases
2004381454-1463
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Hb as a Prognostic Factor for AIDS-Defining
Illness (ADI)

• Incidence rate ratio (IRR) events/100
  person-years
• Hb lt 10 g/dL 8.62 (95 CI5.52, 13.3)
• Hb 10-11 g/dL 7.31 (95 CI4.52, 11.7)
• Hb 11-12 g/dL 3.93 (95 CI2.44, 6.35)
• Hb gt 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. 199913943-950
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Recovery From Anemia Is Associated With Improved
Survival (N 3203)
Sullivan PS, et al. Blood. 199891301-308
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Progression of Hb During HAART
Servais J, et al. JAIDS. 200128221-225
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Association Between Anemia Treatments and Death
Rates
Moore R. JAIDS. 19981929
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Treatment of HIV and Treatment-related Anemia

• Epoetin alfa
• Initiate Treatment
• Symptomatic vs asymptomatic
• Hb lt 11 g/dL
• EPO lt 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 lt100ng/mL, transferrin saturation lt20
Volberding P et al., Clinical Infectious Diseases
2004381454-1463
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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
  patients 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 lt 11 g/dL, EPO lt 500 mU/mL
• Epoetin alfa (40,000 Units QW)
• RBC Transfusions