• Cytomegalovirus (CMV) • Herpes simplex virus (HSV) • Aphthous ulceration
P: Plan
Diagnostic Evaluation
Oropharyngeal candidiasis Clinical examination alone usually is diagnostic. If the diagnosis is unclear, organisms may be detected on smear or culture if necessary.
• On a potassium hydroxide (KOH) preparation of a smear collected by gentle scraping of the affected area with a wooden tongue depressor, visible hyphae or blastospheres on KOH mount indicate Candida infection.
• Culture is diagnostic and may detect non- albicans species in cases resistant to first-line therapies. Sensitivities also may be needed in such cases to diagnose azole-resistant infections.
Esophageal candidiasis
A presumptive diagnosis usually can be made with a recent onset of typical symptoms, especially in the presence of thrush, and empiric antifungal therapy may be started as a diagnostic trial. If the patient fails to improve clinically after 3-7 days of therapy, endoscopy should be performed for a definitive diagnosis.
Treatment
Treatment of oropharyngeal candidiasis • Oral therapy is convenient and very effective
as first-line treatment. Note that azole antifungal drugs are not recommended for use during pregnancy. Topical therapy is less expensive, safe for use during pregnancy, and effective for mild to moderate disease. All therapies should be given for 7-14 days. • Preferred oral therapy: Fluconazole 100 mg
PO QD
• Preferred topical therapy:
• Clotrimazole troches 10 mg dissolved in the mouth 5 times daily
• Miconazole mucoadhesive tablet 50 mg PO QD
• Alternative oral therapy:
• Itraconazole oral solution 200 mg PO QD • Posaconazole oral solution 400 mg PO
BID for 1 day, then 400 mg PO QD (Note: These agents may present a greater risk of drug interactions (see “Potential ARV Interactions,” below) and hepatotoxicity than do fluconazole or topical treatments)
• Alternative topical therapy: Nystatin oral suspension 4-6 mL “swish and swallow” QID or 1-2 pastilles 4-5 times daily Treatment of esophageal candidiasis • Duration of therapy: 14-21 days
• Preferred therapy:
• Fluconazole 100 mg PO (up to 400 mg) QD; IV therapy can be given if the patient is unable to swallow pills.
• Itraconazole oral solution 200 mg PO QD • Alternative therapy:
• Voriconazole 200 mg PO or IV BID • Posaconazole 400 mg PO BID • IV therapy with an echinocandin
Sec tion 6: C omor bidities , Coinf ec tions , and C omplications
(caspofungin, micafungin, anidulafungin), or amphotericin, if the patient is unable to tolerate PO therapy (Note: Treatment with echinocandins is associated with a higher rate of relapse; see “Potential ARV Interactions,” below, regarding potential drug-drug interactions between voriconazole or posaconazole and ARVs) Treatment of refractory candidiasis Oral or esophageal candidiasis that does not improve after at least 7-14 days of appropriate antifungal therapy can be considered refractory to treatment. The primary risk factors for development of refractory candidiasis are CD4 counts of <50 cells/µL and prolonged, chronic antifungal therapy (especially with azoles). In such cases, it is important to confirm the diagnosis of candidiasis. As noted, other infections such as HSV, CMV, and aphthous ulcerations can cause similar symptoms. Once refractory candidiasis is confirmed, several treatment options are available, including the following:
• Posaconazole 400 mg PO BID
• Itraconazole oral solution ≥200 mg PO QD • Voriconazole 200 mg PO or IV BID (see
“Potential ARV Interactions,” below)
• Therapy with an echinocandin (caspofungin 50 mg QD; micafungin 150 mg QD;
anidulafungin 100 mg for 1 dose, then 50 mg QD), or amphotericin B deoxycholate or lipid preparation
(Note: Treatment with echinocandins is associated with a higher rate of relapse. See “Potential ARV Interactions,” below, for information on potential drug interactions.)
The choice of treatment depends upon
anticipated drug-drug interactions, the patient’s preferences and tolerability, availability of medications, and the provider’s experience. Consult with an HIV or infectious disease expert for advice about treatment regimens.
Maintenance therapy
Use caution when considering chronic maintenance therapy, because it has been associated with refractory and azole-resistant candidiasis, as noted above. Fluconazole 100 mg PO QD or TIW can be effective for patients who have had multiple or severe recurrences of oral disease (azole sensitive). Fluconazole 100-200 mg PO QD or posaconazole 400 mg PO BID (see “Potential ARV Interactions,” below) can be considered for patients who have had frequent or severe recurrent esophageal candidiasis.
There are no data to guide this decision; it is reasonable to discontinue maintenance therapy in patients who achieve immunologic responses on fully suppressive ART (i.e., with an increase in CD4 count to ≥200 cells/µL). Patients with fluconazole-refractory oropharyngeal or esophageal disease who respond to IV echinocandins are recommended to take posaconazole or voriconazole suppression until they achieve immune reconstitution on ART, because of high relapse rates.
Potential ARV Interactions There may be significant drug-drug interac- tions between certain systemic antifungals (particularly itraconazole, voriconazole, and posaconazole) and ritonavir-boosted pro- tease inhibitors (PIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), elvitegravir/ cobicistat, or maraviroc. Some combinations are contraindicated and others require dos- age adjustment of the ARV, the antifungal, or both. Check for adverse drug interactions before prescribing. For example, voriconazole use is not recommended for patients taking ritonavir-boosted PIs, and dosage adjustment of both voriconazole and NNRTIs may be re- quired when voriconazole is used concurrently with NNRTIs. See relevant tables in the U.S. Department of Health and Human Services Guidelines for the Use of Antiretroviral Agents in
HIV-1-Infected Adults and Adolescents, or consult
392 | Guide for HIV/AIDS Clinical Care Sec tion 6: C omor bidities , Coinf ec tions , and C omplications
Patient Education
• Patients should maintain good oral hygiene by brushing teeth after each meal.
• A soft toothbrush should be used to avoid mouth trauma.
• Advise patients to rinse the mouth of all food before using lozenges or liquid medications.
• Tell patients to avoid foods or liquids that are very hot in temperature or very spicy. • Patients who have candidiasis under a
denture or partial denture should remove the prosthesis before using topical agents such as clotrimazole or nystatin. When not in use, the prosthesis should be stored in a chlorhexidine solution.
• Pregnant women and women who may become pregnant should avoid azole drugs (e.g., fluconazole, itraconazole, voriconazole) during pregnancy because they can cause skeletal and craniofacial abnormalities in infants.
• Patients should be informed of proper storage of oral solutions (e.g., refrigeration requirements).
References
• Aberg JA, Gallant JE, Ghanem KG et al.; HIV Medicine Association of the Infectious Diseases Society of America. Primary Care Guidelines for the Management of Persons Infected With HIV: 2013 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jan;58(1):e1-e34.
• Klein RS, Harris CA, Small CB, et al. Oral candidiasis in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome. N Engl J Med. 1984 Aug 9;311(6):354-8.
• Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1- infected adults and adolescents. Department of Health and Human Services. Available at aidsinfo.nih.gov/guidelines. Accessed December 1, 2013.
• Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at aidsinfo.nih.gov/guidelines. Accessed December 1, 2013.
• Pappas PG, Kauffman CA, Andes D, et al.; Infectious Diseases Society of America. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009 Mar 1;48(5):503-35. • Skiest DJ, Vazquez JA, Anstead GM, et al.
Posaconazole for the treatment of azole- refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection. Clin Infect Dis. 2007 Feb 15;44(4):607-14.
Sec tion 6: C omor bidities , Coinf ec tions , and C omplications
S: Subjective
The patient may complain of itching, burning, or swelling of the labia and vulva; a thick white or yellowish vaginal discharge; painful intercourse; and pain and burning on urination.
The most important elements in the history include the following:
• Type and duration of symptoms • Previous vaginal yeast infection • Oral contraceptive use
• Recent or ongoing broad-spectrum antibiotic therapy
• Recent corticosteroid therapy
• Sexual exposures (to evaluate for sexually transmitted diseases) • Diabetes history • Cushing syndrome • Obesity • Hypothyroidism • Pregnancy
• Use of douches, vaginal deodorants, or bath additives
O: Objective
Perform a focused physical examination of the external genitalia, vagina, and cervix. This may reveal inflammation of the vulva with evidence of discharge on the labial folds and vaginal opening. Speculum examination usually reveals a thick, white discharge with plaques adhering to the vaginal walls and cervix. Bimanual examination should not elicit pain or tenderness and otherwise should be normal.
A: Assessment
Rule out other causes of vaginal discharge and pruritus:
• Bacterial vaginosis • Atrophic vaginitis
• Chemical or mechanical causes • Trichomoniasis
• Gonorrhea, chlamydia, and other sexually transmitted diseases
• Scabies • Pediculosis
Candidiasis, Vulvovaginal
Background
Vulvovaginal candidiasis is a yeast infection caused by several types of Candida, typically Candida albicans. This disease is common in all women, but may occur more frequently and more severely in immunocompromised women.
Although refractory vaginal Candida infections by themselves should not be considered indicators of HIV infection, they may be the first clinical manifestation of HIV infection and can occur early in the course of disease (at CD4 counts of >500 cells/µL). The frequency of vaginal candidiasis tends to increase as CD4 counts decrease; however, this may be attributable in part to increased use of antibiotics among women with advanced HIV infection.
Risk factors for candidiasis include diabetes mellitus and the use of oral contraceptives, corticosteroids, or antibiotics.
394 | Guide for HIV/AIDS Clinical Care Sec tion 6: C omor bidities , Coinf ec tions , and C omplications
P: Plan
Diagnostic Evaluation
A presumptive diagnosis is made on the basis of the clinical presentation and potassium hydroxide (KOH) preparation:
• Perform microscopic examination of a KOH preparation of vaginal secretions. This usually reveals pseudohyphae and Candida spores (presumptive diagnosis).
• Definitive diagnosis rarely is needed, but may be made by analysis of a culture of vaginal secretions; this may be useful if azole-resistant or non-albicans species are suspected.
• In the presence of urinary tract symptoms (beyond external vulvar burning), perform urinalysis, culture, or both on a clean-catch urine specimen.
• Consider testing for gonorrhea and chlamydia in patients with a history of possible sexual exposure.