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 Users are cautioned that, owing to the rapidly changing field of HIV care, this information could become out of date quickly.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 2 May 2013 www. aidsetc. org

Coccidioidomycosis: Epidemiology 3 § 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 CD 4 count <250 cells/µL § Incidence and severity lower after broader use of ART May 2013 www. aidsetc. org

Coccidioidomycosis: Clinical Manifestations § Severity associated with lower CD 4 counts, lack of HIV suppression § In HIV infection, 6 common syndromes: § § § 4 Focal pneumonia Diffuse pneumonia (presents like PCP) Cutaneous involvement Meningitis Liver or lymph node involvement Positive coccidioidal serology tests without evidence of localized infections May 2013 www. aidsetc. org

Coccidioidomycosis: Clinical Manifestations (2) § Focal pneumonia most common if CD 4 count >250 cells/µL § Other syndromes usually occur with more advanced immunosuppression § Meningitis: headache, progressive lethargy, fever, nausea or vomiting, confusion 5 May 2013 www. aidsetc. org

Coccidioidomycosis: Manifestations Chest X ray: disseminated coccidioidomycosis 6 Credit: Huang L, MD; HIV In. Site May 2013 www. aidsetc. org

Coccidioidomycosis: Diagnosis § Culture of clinical specimens § Histopathology § Blood cultures (positive in <50%) § Coccidioidal Ig. M and Ig. G serology (EIA, immunodiffusion, classical tube precipitin, complement fixation): useful but poorer sensitivity in patients with low CD 4 counts § CSF analysis: typically shows lymphocytic pleocytosis, CSF glucose <50 mg/d. L, 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 7 May 2013 www. aidsetc. org

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) 8 May 2013 www. aidsetc. org

Coccidioidomycosis: Prevention § Preventing disease § Primary prophylaxis not recommended § For HIV-infected persons in endemic regions: yearly serologic testing is reasonable § If new positive Ig. M or Ig. G serologic test and CD 4 count <250 cells/µL § Fluconazole 400 mg PO QD § Outside endemic regions: routine testing not useful and should not be done 9 May 2013 www. aidsetc. org

Coccidioidomycosis: Treatment § Treatment consists of 2 phases: induction and maintenance § Total duration of therapy ≥ 12 months 10 May 2013 www. aidsetc. org

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 11 May 2013 www. aidsetc. org

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 12 May 2013 www. aidsetc. org

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 13 May 2013 www. aidsetc. org

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 14 May 2013 www. aidsetc. org

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 15 May 2013 www. aidsetc. org

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 16 May 2013 www. aidsetc. org

Coccidioidomycosis: Preventing Recurrence § Consider lifelong suppressive therapy if CD 4 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 17 May 2013 www. aidsetc. org

Coccidioidomycosis: Preventing Recurrence (2) Discontinuing secondary prophylaxis: § Focal pneumonia: § May discontinue after 12 months of therapy if CD 4 ≥ 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 18 May 2013 www. aidsetc. org

Coccidioidomycosis: Considerations in Pregnancy § More likely to disseminate if acquired during 2 nd or 3 rd trimester § Amphoteracin B or its lipid formulations are preferred initial regimen § At delivery, evaluate neonate for renal dysfunction and hypokalemia 19 May 2013 www. aidsetc. org

Coccidioidomycosis: Considerations in Pregnancy (2) § Azoles: avoid in 1 st 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 20 May 2013 www. aidsetc. org

Websites to Access the Guidelines § http: //www. aidsetc. org § http: //aidsinfo. nih. gov 21 May 2013 www. aidsetc. org

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 22 May 2013 www. aidsetc. org