Guidelines for Prevention and Treatment of Opportunistic Infections

Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents Aspergillosis 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 Users are cautioned that, owing to the rapidly changing field of HIV care, this information could become out of date quickly.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

Aspergillosis: Epidemiology § Caused by Aspergillus fumigatus, occasionally by other Aspergillus species § Invasive aspergillosis is rare in HIV-infected persons § Risk factors: low CD 4 count (<100 cells/µL), neutropenia, use of corticosteroids, exposure to broad-spectrum antibiotics, underlying lung disease § Less common with widespread use of potent ART 3 May 2013 www. aidsetc. org

Aspergillosis: Clinical Manifestations § 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 4 May 2013 www. aidsetc. org

Aspergillosis: Diagnosis § 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 5 May 2013 www. aidsetc. org

Aspergillosis: Preventing Disease § 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 6 May 2013 www. aidsetc. org

Aspergillosis: Treatment § Not systematically evaluated in HIV-infected patients § Preferred: § Voriconazole 6 mg/kg IV Q 12 H for 1 day, then 4 mg/kg IV Q 12 H until clinical improvement, then 200 mg PO Q 12 H § Significant interactions with protease inhibitors and efavirenz § Duration of therapy: not established; continue at least until CD 4 >200 cells/µL and infection appears resolved 7 May 2013 www. aidsetc. org

Aspergillosis: Treatment (2) § 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 CD 4 >200 cells/µL and infection appears resolved 8 May 2013 www. aidsetc. org

Aspergillosis: ART Initiation § 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 9 May 2013 www. aidsetc. org

Aspergillosis: Monitoring and Adverse Events § 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 10 May 2013 www. aidsetc. org

Aspergillosis: Treatment Failure § 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 11 May 2013 www. aidsetc. org

Aspergillosis: Preventing Recurrence § Chronic maintenance: insufficient data to recommend for or against 12 May 2013 www. aidsetc. org

Aspergillosis: Considerations in Pregnancy § 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 1 st trimester § Echinocandins: bone and visceral abnormalities in animals; avoid in 1 st trimester 13 May 2013 www. aidsetc. org

Websites to Access the Guidelines § http: //www. aidsetc. org § http: //aidsinfo. nih. gov 14 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 15 May 2013 www. aidsetc. org