Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents Mucocutaneous 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

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 Users are cautioned that, owing to the rapidly changing field of HIV care, this information could become out of date quickly.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

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 May 2013 www.aidsetc.org

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 May 2013 www.aidsetc.org

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 May 2013 www.aidsetc.org

Mucocutaneous Candidiasis: Clinical Manifestations (3) Esophageal candidiasis Credit: P. Volberding, MD; UCSF Center for HIV Information Image Library May 2013 www.aidsetc.org

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 May 2013 www.aidsetc.org

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 May 2013 www.aidsetc.org

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. . May 2013 www.aidsetc.org

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. May 2013 www.aidsetc.org

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 May 2013 www.aidsetc.org

Mucocutaneous Candidiasis: ART Initiation No special considerations regarding ART initiation May 2013 www.aidsetc.org

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 May 2013 www.aidsetc.org

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 May 2013 www.aidsetc.org

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) May 2013 www.aidsetc.org

Mucocutaneous Candidiasis: Preventing Recurrence Stopping secondary prophylaxis: No data; reasonable to stop when CD4 >200 cells/µL after ART initiation May 2013 www.aidsetc.org

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 May 2013 www.aidsetc.org

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