1. Prepared by the AETC National Coordinating Resource Center based on recommendations from the CDC, National Institutes of Health, and HIV Medicine Association/Infectious Diseases Society of America Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents Aspergillosis Slide Set

2. 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 Users are cautioned that, owing to the rapidly changing field of HIV care, this information could become out of date quickly.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 Coordinating Resource Center http://www.aidsetc.org About This Presentation May 2013www.aidsetc.org 2

3. May 2013www.aidsetc.org 3  Epidemiology  Clinical Manifestations  Diagnosis  Prevention  Treatment  Considerations in Pregnancy Aspergillosis

4.  Caused by Aspergillus fumigatus, occasionally by other Aspergillus species  Invasive aspergillosis is rare in HIV-infected persons  Risk factors: low CD4 count (<100 cells/µL), neutropenia, use of corticosteroids, exposure to broad-spectrum antibiotics, underlying lung disease  Less common with widespread use of potent ART Aspergillosis: Epidemiology May 2013www.aidsetc.org 4

5.  Respiratory  Invasive pneumonia: fever, cough, dyspnea, chest pain, hemoptysis, hypoxemia; on CXR, diffuse, focal, or cavitary infiltrates, “halo” of low attenuation around a pulmonary nodule (or “air crescent” on CT)  Tracheobronchitis: fever, cough, dyspnea, stridor, wheezing, airway obstruction; tracheal pseudomembrane (multiple ulcerative or plaque-like lesions) seen on bronchoscopy  Other extrapulmonary forms include: sinusitis, cutaneous disease, osteomyelitis Aspergillosis: Clinical Manifestations May 2013www.aidsetc.org 5

6.  Definitive diagnosis:  Histopathology: tissue invasion by septate hyphae, with positive culture for Aspergillus spp  Probable diagnosis of invasive pulmonary disease:  Isolation of Aspergillus spp from respiratory secretions or septate hyphae consistent with Aspergillus in respiratory samples, with typical CT findings  ELISA test for galactomannan: sensitivity better for BAL than for serum; high specificity; not well studied in HIV Aspergillosis: Diagnosis May 2013www.aidsetc.org 6

7.  Preventing exposure:  Aspergillus spp are ubiquitous in the environment; exposure is not avoidable  Avoid dusty environments to decrease exposure to spores  Preventing disease  No data in HIV-infected persons; currently not recommended  Posaconazole effective in patients with certain hematologic malignancies and neutropenia Aspergillosis: Preventing Disease May 2013www.aidsetc.org 7

8.  Not systematically evaluated in HIV-infected patients  Preferred:  Voriconazole 6 mg/kg IV Q12H for 1 day, then 4 mg/kg IV Q12H until clinical improvement, then 200 mg PO Q12H  Significant interactions with protease inhibitors and efavirenz  Duration of therapy: not established; continue at least until CD4 >200 cells/µL and infection appears resolved Aspergillosis: Treatment May 2013www.aidsetc.org 8

9.  Alternative:  Lipid formulation amphotericin B 5 mg/kg IV QD  Amphotericin B deoxycholate 1 mg/kg IV QD  Caspofungin 70 mg IV for 1 dose, then 50 mg IV QD  Micafungin 100-150 mg IV QD  Anidulafungin 200 mg IV for 1 dose, then 100 mg IV QD  Posaconazole 200 mg PO 4 times per day until clinical improvement, then 400 mg PO BID  Duration of therapy: not established; continue at least until CD4 >200 cells/µL and infection appears resolved Aspergillosis: Treatment (2) May 2013www.aidsetc.org 9

10.  Start ART as soon as possible after start of antifungal therapy  IRIS has rarely been reported  Triazoles have complex, sometimes bidirectional interactions with certain ARVs; dosage adjustments may be needed Aspergillosis: ART Initiation May 2013www.aidsetc.org 10

11.  If new or recurrent signs and symptoms, evaluate for relapse or recurrence  IRIS reported rarely  Limited data regarding monitoring of galactomannan levels in response to therapy Aspergillosis: Monitoring and Adverse Events May 2013www.aidsetc.org 11

12.  Prognosis is poor in advanced immunosuppression without effective ART  No data to guide management of treatment failure  If voriconazole used initially, consider change to amphotericin B, or echinocandins in combination with voriconazole or amphotericin B Aspergillosis: Treatment Failure May 2013www.aidsetc.org 12

13.  Chronic maintenance: insufficient data to recommend for or against Aspergillosis: Preventing Recurrence May 2013www.aidsetc.org 13

14.  Amphotericin B or its lipid formulations are preferred initial regimen  At delivery, evaluate neonate for renal dysfunction and hypokalemia  Voriconazole and posaconazole: teratogenic and embryotoxic in animals; generally avoid in pregnancy, especially 1st trimester  Echinocandins: bone and visceral abnormalities in animals; avoid in 1st trimester Aspergillosis: Considerations in Pregnancy May 2013www.aidsetc.org 14

15.  AIDS Info: http://aidsinfo.nih.gov Access the Guidelines Online May 2013www.aidsetc.org 15

16. May 2013www.aidsetc.org 16  This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in May 2013  See the AETC NCRC website for the most current version of this presentation: http://www.aidsetc.org About This Slide Set