Transcript Guidelines for Prevention and Treatment of Opportunistic Infections

Guidelines for Prevention and Treatment of
Opportunistic Infections in HIV-Infected
Adults and Adolescents
Coccidioidomycosis 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
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become out of date quickly.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
<250 cells/µL
 Incidence and severity lower after broader
use 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:
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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 >250 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
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Credit: Huang L, MD; HIV InSite
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Coccidioidomycosis: Diagnosis
 Culture of clinical specimens
 Histopathology
 Blood cultures (positive in <50%)
 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 <50 mg/dL, CSF protein normal or mildly
elevated; complement fixation usually positive;
culture positive in <1/3
 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 <250 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:
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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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Coccidioidomycosis:
Monitoring 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 <250 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 >25% 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
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