Module 6
Oropharyngeal Candidiasis
in Persons Living with HIV/AIDS
Oropharyngeal Candidiasis in
Persons Living with HIV/AIDS
David A. Reznik, D.D.S.
Chief, Dental Service
Grady Health System
Atlanta, Georgia
Angular Cheilitis
• The clinical presentation of Angular cheilitis
(AC) is erythema and/or fissuring of the corners
of the mouth.
• AC can occur with or without the presence of
erythematous and/or pseudomembranous
candidiasis.
• Treatment involves the use of a topical
antifungal cream directly applied to the affected
areas four times a day for the two-week
treatment period.
Angular Cheilitis
Angular Cheilitis
•
Erythematous candidiasis (EC)
• EC presents as a red, flat, subtle lesion
either on the dorsal surface of the tongue
and/or the hard/soft palates.
• EC tends to be symptomatic with patients
complaining of oral burning, most
frequently while eating salty or spicy
foods or drinking acidic beverages.
Erythematous candidiasis (EC)
• Clinical diagnosis is based on
appearance, taking into consideration the
person’s medical history and virologic
status.
• The presence of fungal hyphae or
blastospores can be confirmed by
performing a potassium hydroxide
preparation.
Erythematous candidiasis (EC)
Erythematous candidiasis (EC)
Erythematous candidiasis (EC)
•
Erythematous candidiasis (EC)
Pseudomembranous
candidiasis (PC)
• PC appears as creamy white curd-like plaques
on the buccal mucosa, tongue and other oral
mucosal surfaces that will wipe away, leaving a
red or bleeding underlying surface.
• The most common organism involved with the
presentation of candidiasis is Candida albicans,
however there are increasing reports of the
increased incidence of non-albicans species. 1
–
1. Powderly WG, Mayer KH, Perfect JR. Diagnosis and treatment of oropharyngeal candidiasis
in patients infected with HIV: a critical reassessment. AIDS Res Hum Retroviruses 1999 Nov
1;15(16):1405-12.
Clinical Diagnosis of PC
• The diagnosis of PC is based on clinical
appearance taking into consideration the
person’s medical history.
• Potassium hydroxide preparation, fungal
culture or biopsy, may be useful in
obtaining an accurate diagnosis.
Mild to Moderate
Pseudomembranous Candidiasis
Mild to Moderate
Pseudomembranous Candidiasis
Moderate to Severe
Pseudomembranous Candidiasis
Moderate to Severe
Pseudomembranous Candidiasis
Azole Resistant
Pseudomembranous
Candidiasis (C. albicans)
Azole Resistant
Pseudomembranous
Candidiasis (C. glabrata)
Trends in Candidiasis in the
HAART-Era
• There has been a decline in the occurrence of
PC in patients who are on successful highly
active retroviral regimens containing protease
inhibitors 2
• A review of the literature suggests that immune
reconstruction alone does not account for this
reduction, but rather the added effect of
protease inhibitors on candidal virulence
factors such as aspartyl protease.3
2 Patton LL, McKaig R, Straauss R, Rogers D, Enron JJ Jr. Changing prevalence of oral manifestations of human immunodeficiency
virus in the era of protease inhibitor therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:299-304.
3 Cauda, R, Tacconelli E, Tumbarello M, Morace G, De Bernardis F, Torosantucci A, Cassone A. Role of protease inhibitors in
preventing recurrent oral candidosis in patients with HIV infection: a prospective case-control study. J Acquir Defic Syndr Hum
Retrovirl, Vol 21(1), May 99.
Treatment of Candidiasis
• Treatment should be based on the extent
of the infection with topical therapies
(nystatin, clotrimazole) utilized for mild to
moderate cases and systemic therapies
(fluconazole) used for moderate to severe
presentations.
• Antifungal therapy should last for two
weeks to reduce the colony forming units
to the lowest level possible to prevent
recurrence.
Azole Resistance
• As HIV disease progresses and
immunosuppression becomes more
severe, the incidence and severity of
oropharyngeal candidiasis increase. The
introduction of oral azoles, most notably
fluconazole, has led to the increased
incidence of azole resistant Candida
albicans as well as the emergence of nonalbicans species such as Candida glabrata,
which are inherently resistant to this class
of drug1
Azole Resistance
• Factors that increase the probability of azole
resistant strains of Candida presenting in the
oral cavity include previous exposure to azoles,
low CD4 count and the presence of nonalbicans species.4,5
• To minimize the risk of resistance, topical
therapies should be considered for first-line
treatment of initial or recurrent cases of mild to
moderate oropharyngeal candidiasis.1
4. Maenza JR, Keruly JC, Moore RD, Chaisson RE, Merz WG, Gallant JE. Risk factors for
fluconazole-resistant candidiasis in human immunodeficiency virus-infected patients.
J Infect Dis 1996 Jan;173(1):219-25
5. Cartledge JD, Midgley J, Gazzard BG. Non-albicans oral candidosis in HIV-positive
patients. J Antimicrob Chemother 1999 Mar;43(3):419-22.
Available Medications Used in
the Management of OPC
• Topical agents
 Clotrimazole troches 10 mg: Dispense 70,
dissolve one troche in mouth 5 times a day
for 14 days
 Nystatin oral suspension 500,000 units:
Swish 5 mls in mouth as long as possible
then swallow, 4 times a day for 14 days
 Nystatin pastilles 100,000 units: dispense 56,
dissolve 1 in mouth 4 times a day for 14 days
Available Medications Used in
the Management of OPC
• Systemic agents
 Fluconazole 100mg: dispense 15 tablets,
take 2 tablets on day 1 followed by 1 tablet a
day for the remainder of the 14 day treatment
period
 Itraconazole oral suspension 10mg/10ml:
dispense 140ml, swish and swallow 10ml
per day for 7 to 14 days. Take medication
without food.
Efficacy of antifungal drugs used in the
treatment of OPC in HIV+ Patients
• Limitations in published literature
 HIV disease status (CD4 count, viral load ) not
reported in ~ 1/2 of the studies
 Antiretroviral therapy reported in only 2 studies,
none involving HAART or protease inhibitors
 Compliance with prescribed drug therapy not
universally assessed
 Speciation of candidal organisms in treatment
failures was rare; drug susceptibility testing not
performed
 Cost-effectiveness analysis not performed
Efficacy of topical antifungal
therapies
• Clinical trials have not been undertaken which
compare the efficacy of the two most frequently
prescribed topical antifungal medications used
in the management of OPC in HIV+ individuals
 nystatin oral suspension
 clotrimazole troches
• The only comparison which can be referenced
include two studies which were designed to
look at the efficacy of two different formulations
of fluconazole.
Selected studies involving
topical antifungal therapies
• Pons et al, 1993, Fluconazole (100 mg) once daily
for 14 days vs Clotrimazole 10 mg troche 5 X daily
for 14 days
 98% C. albicans at baseline
 334 enrolled, 288 evaluated for efficacy
 Fluconazole arm: 91% complete clinical response:
7% clinical improvement
 Clotrimazole arm: 85% complete clinical
response: 9% clinical improvement
 Difference in clinical response: Group 1 vs 2 p= ns
Selected studies involving
topical antifungal therapies
• Pons et al, 1997, Fluconazole liquid suspension
100 mg 1X daily for 14 days vs nystatin oral
suspension 500,000 Units 4 X daily for 14 days
 95% C. albicans at baseline
 167 enrolled, 138 evaluated for efficacy
 Fluconazole suspension arm: 87% complete
cure, 12% improvement
 Nystatin liquid arm: 52% complete cure, 16%
improvement
 Difference in clinical response: P < .001
Conclusions
• Oropharyngeal candidiasis is still a
common oral opportunistic infection 2
• Judicious use of systemic antifungal
therapies is warranted. 1
2.Patton LL, McKaig R, Straauss R, Rogers D, Enron JJ Jr. Changing prevalence of oral
manifestations of human immunodeficiency virus in the era of protease inhibitor therapy. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:299-304
1.Powderly WG, Mayer KH, Perfect JR. Diagnosis and treatment of oropharyngeal candidiasis in
patients infected with HIV: a critical reassessment. AIDS Res Hum Retroviruses 1999 Nov
1;15(16):1405-12.
Conclusions
• There is an increased incidence in
fluconazole refractory oropharyngeal
candidiasis 4,5
• Factors which lead to resistance include
previous exposure to systemic azoles and
low CD4 counts 4
4.Maenza JR, Keruly JC, Moore RD, Chaisson RE, Merz WG, Gallant JE. Risk factors for
fluconazole-resistant candidiasis in human immunodeficiency virus-infected patients.
J Infect Dis 1996 Jan;173(1):219-25
5.Cartledge JD, Midgley J, Gazzard BG. Non-albicans oral candidosis in HIV-positive
patients. J Antimicrob Chemother 1999 Mar;43(3):419-22