Prevention and Treatment of Coccidioidomycosis in HIV-Infected Adults

1. 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

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 Users are cautioned that, owing to the rapidly changing field of HIV care, this information could become out of date quickly.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

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

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 www.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) www.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 www.aidsetc.org

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

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

22. 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 www.aidsetc.org