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1. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and AdolescentsMucocutaneous Candidiasis 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 Users are cautioned that, owing to the rapidly changing field of HIV care, this information could become out of date quickly.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. Mucocutaneous Candidiasis:Epidemiology • Oropharyngeal and esophageal candidiasis are common • Most common in patients with CD4 count <200 cells/µL • Prevalence lower in patients on ART • Vulvovaginal candidiasis • Occurs in HIV-noninfected women; does not indicate immunosuppression • In advanced immunosuppression, may be more severe or recur more frequently • Usually caused by Candida albicans; other species (especially C glabrata) seen in advanced immunosuppression, refractory cases www.aidsetc.org

4. Mucocutaneous Candidiasis:Clinical Manifestations • Oropharyngeal (thrush): • Pseudomembranous: painless, creamy white plaques on buccal or oropharyngeal mucosa or tongue; can be scraped off easily • Erythematous: patches on anterior or posterior upper palate or tongue • Angular cheilosis • Esophageal: • Retrosternal burning pain or discomfort, odynophagia, fever; on endoscopy, whitish plaques with or without mucosal ulceration • Vulvovaginal: • Creamy discharge, mucosal burning and itching www.aidsetc.org

5. Mucocutaneous Candidiasis:Clinical Manifestations (2) Pseudomembranous candidiasis Credit: Pediatric AIDS Pictorial Atlas, Baylor International Pediatric AIDS Initiative Erythematous candidiasis Credit: D. Greenspan, DSC, BDS;HIV InSite www.aidsetc.org

6. Mucocutaneous Candidiasis:Clinical Manifestations (3) Esophageal candidiasis Credit: P. Volberding, MD; UCSF Center for HIV Information Image Library www.aidsetc.org

7. Mucocutaneous Candidiasis:Diagnosis • Oropharyngeal: • Usually clinical diagnosis • For laboratory confirmation: KOH preparation; culture • Esophageal: • Empiric diagnosis: symptoms and response to trial of therapy (usually appropriate before endoscopy); visualization of lesions + fungal smear or brushings • Endoscopy with histopathology and culture • Vulvovaginal: • Clinical diagnosis, and KOH preparation www.aidsetc.org

8. Mucocutaneous Candidiasis:Prevention • Preventing exposure • Candida are common mucosal commensals; no measures to reduce exposure • Primary prophylaxis • Not recommended: mucosal disease has low mortality; acute therapy is effective; concern for drug resistance, drug interactions, expense www.aidsetc.org

9. Mucocutaneous Candidiasis:Treatment Oropharyngeal • Preferred (7-14 days) • Fluconazole 100 mg PO QD • Clotrimazole troches 10 mg PO 5 times daily • Miconazole mucoadhesive buccal tablet 50 mg QD to canine fossa • Alternative • Itraconazole* oral solution 200 mg PO QD • Posaconazole* oral solution 400 mg PO BID x 1, then 400 mg QD • Nystatin suspension 4-6 mL QID or 1-2 flavored pastilles 4-5 times daily * May have significant drug interactions with certain ARV medications; consult information on drug interactions before coadministering with ARVs. . www.aidsetc.org

10. Mucocutaneous Candidiasis:Treatment (3) Esophageal • Systemic therapy required • Preferred (14-21 days) • Fluconazole 100 mg (up to 400 mg) PO or IV QD • Itraconazole* oral solution 200 mg PO QD • Alternative • Voriconazole* 200 mg PO BID • Posaconazole* 400 mg PO BID • Caspofungin 50 mg IV QD • Micafungin 150 mg IV QD • Anidulafungin 100 mg IV x 1, then 50 mg IV QD • Amphotericin B deoxycholate 0.6 mg/kg IV QD • Amphotericin B (lipid formulation) 3-4 mg/kg IV QD * May have significant drug interactions with certain ARV medications; consult information on drug interactions before coadministering with ARVs. www.aidsetc.org

11. Mucocutaneous Candidiasis:Treatment (5) Vulvovaginal, uncomplicated • Preferred • Fluconazole 150 mg PO for 1 dose • Topical azoles for 3-7 days • Alternative • Topical nystatin 100,000 units/day for 14 days • Itraconazole oral solution 200 mg QD for 3 days • Severe or recurrent • Fluconazole 100-20 mg PO or topical antifungal for ≥7 days www.aidsetc.org

12. Mucocutaneous Candidiasis:ART Initiation • No special considerations regarding ART initiation www.aidsetc.org

13. Mucocutaneous Candidiasis:Monitoring • Response usually rapid (48-72 hours) • Adverse effects: • Rare with topical treatment • For prolonged oral azole treatment (>21 days), monitor for hepatoxicity • No reports of IRIS www.aidsetc.org

14. Mucocutaneous Candidiasis:Treatment Failure • Persistence of signs and symptoms after 7-14 days of appropriate therapy • Testing (eg, culture) needed to confirm treatment failure owing to azole resistance • Refractory disease: • Posaconazole effective in 75% of azole-refractory candidiasis • Oral itraconazole effective in most fluconazole-refractory mucosal candidiasis • Consider anidulafungin, caspofungin, micafungin, voriconazole • Amphotericin B usually effective www.aidsetc.org

15. Mucocutaneous Candidiasis:Preventing Recurrence • ART and immune reconstitution reduce recurrences • For oropharyngeal or vulvovaginal, chronic maintenance therapy generally not recommended • If frequent or severe recurrences, consider fluconazole 100 mg PO QD or TIW (oral); fluconazole 150 mg PO weekly (vaginal) • For esophageal, consider fluconazole 100-200 mg PO QD or posaconazole 400 mg PO BID • Azole-refractory oropharyngeal or esophageal candidiasis: recommended until immune reconstitution on ART (if responded to echinocandins, voriconazole, or posaconazole) www.aidsetc.org

16. Mucocutaneous Candidiasis:Preventing Recurrence • Stopping secondary prophylaxis: • No data; reasonable to stop when CD4 >200 cells/µL after ART initiation www.aidsetc.org

17. Mucocutaneous Candidiasis:Considerations in Pregnancy • Diagnosis: as in nonpregnant adults • Oral or vaginal candidiasis: topical therapy preferred • For invasive or refractory esophageal candidiasis in 1st trimester, amphotericin B recommended (rather than fluconazole or itraconazole) • High-dose fluconazole and itraconazole: teratogenic in animal studies; teratogenic effects not seen in infants born to women receiving single doses • Systemically absorbed azoles should not be used for prophylaxis during pregnancy • Anidulafungin, caspofungin, micafungin, posaconazole, voriconazole are teratogenic in animals; no human data: not recommended www.aidsetc.org

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

19. 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