Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents Histoplasmosis Slide Set

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Guidelines for Prevention and Treatment of
Opportunistic Infections in HIV-Infected Adults
and AdolescentsHistoplasmosis Slide Set

• Prepared by the AETC National Resource Center
  based on recommendations from the CDC, National
  Institutes of Health, and HIV Medicine
  Association/Infectious Diseases Society of
  America

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About This Presentation
These slides were developed using recommendations
published in May 2013. The intended audience is
clinicians involved in the care of patients with
HIV. Users are cautioned that, owing to the
rapidly changing field of HIV care, this
information could become out of date quickly.
Finally, it is intended that these slides be used
as prepared, without changes in either content or
attribution. Users are asked to honor this
intent. -AETC National Resource
Center http//www.aidsetc.org
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Histoplasmosis Epidemiology

• Caused by Histoplasma capsulatum
• Endemic in midwest United States, Puerto Rico,
  Latin America
• Occurs in up to 5 of HIV-infected individuals in
  endemic areas
• In nonendemic areas, usually seen in those who
  previously lived in endemic area

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Histoplasmosis Epidemiology (2)

• Acquired by inhalation
• Risks include working with surface soil,
  cleaning chicken coops contaminated with
  droppings disturbing bird or bat droppings
  exploring caves cleaning, remodeling, or
  demolishing old buildings

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Histoplasmosis Epidemiology (3)

• Reactivation of latent infection may occur
• Systemic illness more likely in patients with CD4
  count lt150 cells/µL
• Pulmonary histoplasmosis may occur with CD4 count
  gt300 cells/µL
• Incidence has declined with use of potent ART

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Histoplasmosis Clinical Manifestations

• Disseminated disease fever, fatigue, weight
  loss, hepatosplenomegaly
• Cough, chest pain, dyspnea in 50
• Shock and multiorgan failure in 10
• Most common in patients with low CD4 count
• Isolated pulmonary disease usually occurs in
  patients with CD4 count gt300 cells/µL
• CNS, GI, and skin manifestations possible
• CNS fever, headache, seizures, focal
  neurological deficits, altered mental status
• GI fever, diarrhea, abdominal pain, weight loss

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Histoplasmosis Clinical Manifestations (2)

• Acute disseminated histoplasmosis, chest X ray
  (L) and CT scan (R)

Credit Images courtesy AIDS Images Library
(www.aids-images.ch)
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Histoplasmosis Clinical Manifestations (3)

• Skin lesions of histoplasmosis

Credit Image courtesy AIDS Images Library
(www.aids-images.ch)
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Histoplasmosis Diagnosis

• Detection of Histoplasma antigen in serum or
  urine
• Sensitive for disseminated histoplasmosis and
  acute pulmonary infection
• In disseminated disease, urine Ag test positive
  in up to 100, serum Ag test positive in up to
  92
• Ag detection in BAL fluid appears sensitive
• Insensitive for chronic pulmonary infection
• Biopsy with histopathologic examination shows
  characteristic budding yeast

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Histoplasmosis Diagnosis (2)

• Culture from blood, bone marrow, respiratory
  secretions, other involved sites (positive in
  gt85, but may take 2-4 weeks)
• Serologic tests usually less useful in AIDS
  patients with disseminated disease, may be
  helpful in patients with higher CD4 counts and
  pulmonary disease

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Histoplasmosis Diagnosis (3)

• Diagnosis of meningitis may be difficult
• CSF cultures and fungal stains 50 sensitive
• Antigen and antibody tests positive in up to 70
  of cases
• Consider presumptive diagnosis of Histoplasma
  meningitis if patient has disseminated
  histoplasmosis and CNS infection that is
  otherwise unexplained
• CSF findings lymphocytic pleocytosis, elevated
  protein, low glucose

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Histoplasmosis Prevention

• Preventing exposure
• In endemic areas, impossible to avoid exposure
  completely
• Avoid higher-risk activities if CD4 lt150 cells/µL
• Primary prophylaxis
• Itraconazole can reduce frequency of disease in
  patients with advanced HIV infection in highly
  endemic areas, but no survival benefit
• Consider itraconazole 200 mg QD for patients with
  CD4 counts lt150 cells/µL who are at high risk of
  infection (occupational exposure or hyperendemic
  area gt10 cases/100 patient-years)
• Discontinuing primary prophylaxis
• Discontinue when CD4 count 150 cells/µL for 6
  monthson effective ART

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Histoplasmosis Treatment

• Acute treatment consists of 2 phases induction
  and maintenance
• Total duration of therapy 12 months

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Histoplasmosis Treatment (2)

• Disseminated histoplasmosis
• Moderate-severe disease
• Induction (2 weeks or until clinically improved)
  
• Preferred liposomal amphotericin B 3 mg/kg IV QD
• Alternative
• Amphotericin B lipid complex or cholesteryl
  sulfate complex 3 mg/kg IV QD
• Maintenance itraconazole 200 mg PO TID for 3
  days, then BID (liquid formulation preferred)
• Duration of therapy 12 months

Adjust dosage based on interactions with ARVs
and itraconazole serum concentration
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Histoplasmosis Treatment (3)

• Disseminated histoplasmosis
• Less-severe disease
• Induction and maintenance
• Preferred Itraconazole 200 mg PO TID for 3 days,
  then BID (liquid formulation preferred)
• Alternative (limited data)
• Posaconazole 400 mg PO BID
• Voriconazole 400 mg PO BID for 1 day, then 200 mg
  PO BID
• Fluconazole 800 mg PO QD
• Duration of therapy 12 months

Adjust dosage based on interactions with ARVs
and itraconazole serum concentration
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Histoplasmosis Treatment (4)

• Meningitis
• Preferred induction (4-6 weeks)
• Liposomal amphotericin B 5 mg/kg IV QD
• Preferred maintenance (12 months plus resolution
  of CSF abnormalities)
• Itraconazole 200 mg PO BID or TID
• Acute pulmonary histoplasmosis in patients with
  CD4 count gt300 cells/µL
• Manage as in nonimmunocompromised

Adjust dosage based on interactions with ARVs
and itraconazole serum concentration
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Histoplasmosis Treatment (5)

• Other antifungals
• Echinocandins not active against H capsulatum
  should not be used

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Histoplasmosis ART Initiation

• Start ART as soon as possible after starting
  antifungal therapy
• IRIS appears to be uncommon
• Triazoles have complex, sometimes bidirectional
  interactions with certain ARVs dosage
  adjustments may be needed

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Histoplasmosis Monitoring and Adverse Events

• Monitor serum or urine Histoplasma antigen
  useful for determining response to therapy
• Increase in level suggests relapse
• Check serum itraconazole levels after 2 weeks of
  therapy or if potential drug interactions
  (absorption of itraconazole can be erratic)
• IRIS is uncommon ART should not be withheld
  because of concern for IRIS

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Histoplasmosis Treatment Failure

• Use liposomal amphotericin B for severely ill
  patients and those who do not respond to initial
  azole therapy
• Consider posaconazole or voriconazole for
  moderately ill patients intolerant of
  itraconazole
• Note significant interactions between
  voriconazole and NNRTIs or ritonavir

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Histoplasmosis Preventing Recurrence

• Secondary prophylaxis
• Long-term suppressive therapy for patients with
  severe disseminated or CNS infection, after 12
  months of treatment and in those who relapse
  despite appropriate therapy
• Preferred itraconazole 200 mg PO
• Alternative fluconazole 400 mg PO QD (less
  effective than itraconazole)
• Voriconazole or posaconazole no data
• May discontinue if 12 months of itraconazole,
  and negative blood cultures, and Histoplasma
  serum Ag lt2 ng/mL, and CD4 count 150 cells/µL on
  ART for 6 months on ART
• Restart if CD4 count decreases to lt150 cells/µL

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Histoplasmosis Considerations in Pregnancy

• Amphotericin B or its lipid formulations are
  preferred initial regimen
• At delivery, evaluate neonate for renal
  dysfunction and hypokalemia
• Azoles avoid in 1st trimester--risk of
  teratogenicity
• Voriconazole and posaconazole teratogenic and
  embryotoxic in animals avoid throughout pregnancy

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Websites to Access the Guidelines

• http//www.aidsetc.org
• http//aidsinfo.nih.gov

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About This Slide Set

• This presentation was prepared by Susa Coffey,
  MD, for the AETC National Resource Center in May
  2013
• See the AETC NRC website for the most current
  version of this presentation
• http//www.aidsetc.org