1. 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

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 Users are cautioned that, owing to the rapidly changing field of HIV care, this information could become out of date quickly.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

3. May 2013www.aidsetc.org 3 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

4. May 2013www.aidsetc.org 4 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

5. May 2013www.aidsetc.org 5 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

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

7. May 2013www.aidsetc.org 7 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

8. May 2013www.aidsetc.org 8 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)

9. May 2013www.aidsetc.org 9 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

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

11. May 2013www.aidsetc.org 11 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

12. May 2013www.aidsetc.org 12 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

13. May 2013www.aidsetc.org 13 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

14. May 2013www.aidsetc.org 14 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

15. May 2013www.aidsetc.org 15 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

16. May 2013www.aidsetc.org 16 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

17. May 2013www.aidsetc.org 17 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

18. May 2013www.aidsetc.org 18 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

19. May 2013www.aidsetc.org 19 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

20. May 2013www.aidsetc.org 20 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

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

22. May 2013www.aidsetc.org 22  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 About This Slide Set