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

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Guidelines for Prevention and Treatment of
Opportunistic Infections in HIV-Infected Adults
and AdolescentsCoccidioidomycosis 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information could become out of date quickly.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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Coccidioidomycosis Epidemiology

• Caused by Coccidioides immitis and C posadasii
• Endemic in southwest United States, parts of
  Central and South America
• Increased risk with extensive exposure to soil
• May cause disease via reactivation of previous
  infection
• Disease may occur in those with no discernible
  immunodeficiency
• Increased risk in HIV patients with CD4 count
  lt250 cells/µL
• Incidence and severity lower after broaderuse of
  ART

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Coccidioidomycosis Clinical Manifestations

• Severity associated with lower CD4 counts, lack
  of HIV suppression
• In HIV infection, 6 common syndromes
• Focal pneumonia
• Diffuse pneumonia (presents like PCP)
• Cutaneous involvement
• Meningitis
• Liver or lymph node involvement
• Positive coccidioidal serology tests without
  evidence of localized infections

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Coccidioidomycosis Clinical Manifestations (2)

• Focal pneumonia most common if CD4 count gt250
  cells/µL
• Other syndromes usually occur with more advanced
  immunosuppression
• Meningitis headache, progressive lethargy,
  fever, nausea or vomiting, confusion

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Coccidioidomycosis Manifestations

• Chest X ray disseminated coccidioidomycosis

Credit Huang L, MD HIV InSite
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Coccidioidomycosis Diagnosis

• Culture of clinical specimens
• Histopathology
• Blood cultures (positive in lt50)
• Coccidioidal IgM and IgG serology (EIA,
  immunodiffusion, classical tube precipitin,
  complement fixation) useful but poorer
  sensitivity in patients with low CD4 counts
• CSF analysis typically shows lymphocytic
  pleocytosis, CSF glucose lt50 mg/dL, CSF protein
  normal or mildly elevated complement fixation
  usually positiveculture positive in lt1/3
• Newer coccidioidomycosis-specific antigen assay
  detects antigen in urine and serum

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Coccidioidomycosis Prevention

• Preventing exposure
• In endemic areas, impossible to avoid exposure
  completely
• HIV-infected persons avoid extensive exposure to
  disturbed soil in endemic areas (eg, excavation
  sites, dust storms)

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Coccidioidomycosis Prevention

• Preventing disease
• Primary prophylaxis not recommended
• For HIV-infected persons in endemic regions
  yearly serologic testing is reasonable
• If new positive IgM or IgG serologic test and CD4
  count lt250 cells/µL
• Fluconazole 400 mg PO QD
• Outside endemic regions routine testing not
  useful and should not be done

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Coccidioidomycosis Treatment

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

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Coccidioidomycosis Treatment

• Severe nonmeningeal infection diffuse pulmonary
  or severely ill with disseminated disease
• Acute phase (continue until clinical
  improvement)
• Preferred
• Amphotericin B deoxycholate 0.7-1.0 mg/kg IV QD
• Lipid-formulation amphotericin B 4-6 mg/kg IV QD
• Alternative add fluconazole or itraconazole to
  amphotericin B (itraconazole preferred for bone
  disease)
• Maintenance therapy (continue indefinitely)
• Fluconazole 400 mg PO QD
• Itraconazole 200 mg PO BID

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Coccidioidomycosis Treatment (2)

• Mild disease focal pneumonia
• Preferred
• Fluconazole 400 mg PO QD
• Itraconazole 200 mg PO BID
• Alternative (limited data)
• Posaconazole 200-400 mg PO BID
• Voriconazole 200 mg PO BID

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Coccidioidomycosis Treatment (3)

• Meningeal infection
• Consult with specialist
• Acute phase
• Preferred fluconazole 400-800 mg IV or PO QD
• Alternative
• Itraconazole 200 mg PO BID
• Posaconazole 200-400 mg PO BID
• Voriconazole 200-400 mg PO BID
• Intrathecal amphotericin B if azoles not
  effective
• Hydrocephalus may develop may need CSF shunt
• Lifelong therapy required relapse in 80 of HIV
  patients with azole therapy discontinued

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Coccidioidomycosis ART Initiation

• Start ART as soon as possible after start of
  antifungal therapy
• IRIS has been reported (1 case)
• Triazoles have complex, sometimes bidirectional
  interactions with certain ARVs dosage
  adjustments may be needed

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CoccidioidomycosisMonitoring and Adverse Events

• Monitor complement-fixing antibody every 12
  weeks useful in assessing response to therapy
• Increase in titer suggests recurrence or
  worsening reassess management
• IRIS 1 reported case

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Coccidioidomycosis Treatment Failure

• Failure of fluconazole or itraconazole
• Severely ill amphotericin B (deoxycholate or
  lipid formulation)
• Not severely ill consider posaconazole 200 mg PO
  BID or voriconazole 200 mg PO BID (limited data
  for both)
• Note significant interactions between
  voriconazole and NNRTIs or ritonavir

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Coccidioidomycosis Preventing Recurrence

• Consider lifelong suppressive therapy if CD4
  count remains lt250 cells/µL
• Preferred
• Fluconazole 400 mg PO QD
• Itraconazole 200 mg PO BID
• Alternative (if patient did not initially respond
  to fluconazole or itraconazole)
• Posaconazole 200 mg PO BID
• Voriconazole 200 mg PO BID

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Coccidioidomycosis Preventing Recurrence (2)

• Discontinuing secondary prophylaxis
• Focal pneumonia
• May discontinue after 12 months of therapy if CD4
  250 cells/µL on effective ART
• Monitor for recurrence (serial chest X rays and
  coccidioidal serology)
• Diffuse pulmonary or nonmeningeal disseminated
  disease
• Relapses in gt25 of cases, even in HIV-uninfected
  patients
• Some would continue therapy indefinitely consult
  with expert
• Meningitis
• Relapses in 80
• Continue therapy lifelong

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Coccidioidomycosis Considerations in Pregnancy

• More likely to disseminate if acquired during 2nd
  or 3rd trimester
• Amphoteracin B or its lipid formulations are
  preferred initial regimen
• At delivery, evaluate neonate for renal
  dysfunction and hypokalemia

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Coccidioidomycosis Considerations in Pregnancy
(2)

• Azoles avoid in 1st trimester--risk of
  teratogenicity
• Coccidioidal meningitis
• Only alternative to azoles is intrathecal
  amphotericin B
• Choice of treatment should be based on
  risk/benefit considerations and in consultation
  with the mother and with infectious disease and
  obstetric experts
• 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