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 Mucocutaneous Candidiasis 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 Users are cautioned that, owing to the rapidly changing field of HIV care, this information could become out of date quickly.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 Mucocutaneous Candidiasis

4.  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 Mucocutaneous Candidiasis: Epidemiology May 2013www.aidsetc.org 4

5.  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 Mucocutaneous Candidiasis: Clinical Manifestations May 2013www.aidsetc.org 5

6. May 2013www.aidsetc.org 6 Erythematous candidiasis Credit: D. Greenspan, DSC, BDS; HIV InSite Pseudomembranous candidiasis Credit: Pediatric AIDS Pictorial Atlas, Baylor International Pediatric AIDS Initiative Mucocutaneous Candidiasis: Clinical Manifestations (2)

7. May 2013www.aidsetc.org 7 Esophageal candidiasis Credit: P. Volberding, MD; UCSF Center for HIV Information Image Library Mucocutaneous Candidiasis: Clinical Manifestations (3)

8.  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 Mucocutaneous Candidiasis: Diagnosis May 2013www.aidsetc.org 8

9.  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 Mucocutaneous Candidiasis: Prevention May 2013www.aidsetc.org 9

10. May 2013www.aidsetc.org 10  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 suspension 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. Mucocutaneous Candidiasis: Treatment

11.  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  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. Mucocutaneous Candidiasis: Treatment (3) May 2013www.aidsetc.org 11

12.  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 Mucocutaneous Candidiasis: Treatment (5) May 2013www.aidsetc.org 12

13.  No special considerations regarding ART initiation Mucocutaneous Candidiasis: ART Initiation May 2013www.aidsetc.org 13

14.  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 Mucocutaneous Candidiasis: Monitoring May 2013www.aidsetc.org 14

15.  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 Mucocutaneous Candidiasis: Treatment Failure May 2013www.aidsetc.org 15

16.  ART and immune reconstitution reduce recurrences  For oropharyngeal or vulvovaginal, chronic suppressive 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 suspension 400 mg PO BID  Azole-refractory oropharyngeal or esophageal candidiasis: recommended until immune reconstitution on ART (if responded to echinocandins, voriconazole, or posaconazole) Mucocutaneous Candidiasis: Preventing Recurrence May 2013www.aidsetc.org 16

17.  Stopping chronic suppressive therapy:  No data; reasonable to stop when CD4 >200 cells/µL after ART initiation Mucocutaneous Candidiasis: Preventing Recurrence (2) May 2013www.aidsetc.org 17

18. May 2013  www.aidsetc.org 18  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 Mucocutaneous Candidiasis: Considerations in Pregnancy

19.  AIDS Info: http://aidsinfo.nih.gov Access the Guidelines Online May 2013www.aidsetc.org 19

20. May 2013www.aidsetc.org 20  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