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Fungal Opportunistic Infections in HIV DiseasePenn Community Infectious Diseases, Penn Presbyterian Medical Center, 51 North 39th Street, Suite W241, Philadelphia, PA 19104 melody.duffalo{at}uphs.upenn.edu Fungal pathogens can lead to many of the complications seen in advanced HIV disease and are commonly identified in HIV-infected populations with decreased immune function. Common fungal organisms affecting individuals with AIDS include Cryptococcus neoformans, various Candida species, and Histoplasma capsulatum. While infection with these organisms can be fatal, appropriate identification and management of the condition can result in reduced mortality and the opportunity for effectivemanagement of HIV disease with highly active antiretroviral therapy. This article describes the clinical presentation and treatment of 3 fungal infections common in the immunocompromised individual with AIDS. Current antifungal therapy for themanagement of these infections is discussed. In addition, the role of newer antifungal agents in the setting of these conditions is reviewed.
Key Words: Fungal disease opportunistic infections HIV disease review treatment References
Palella FJ, Delaney KM, Moorman AC, et al. Decliningmorbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998;338:853-860. Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report, 2003. Vol 15. Atlanta, Ga: US Department of Health and Human Services, Center for Disease Control and Prevention; 2004. Available at: http://www.cdc.gov/hiv/stats/hasrlink.htm. Fichtenbaum CJ. Candidiasis. In: Dolin R, Masur H, Saag M, eds. AIDS Therapy. 2nd ed. Philadelphia, Pa: Churchill-Livingstone; 2003:531-542. Cauda R, Tacconelli E, Tumbarello M, et al. Role of protease inhibitors in preventing recurrent oral candidiasis in patientswith HIV infection: a prospective case-control study. J Acquir Immune Defic Syndr. 1999;21:20-20.[Web of Science][Medline] [Order article via Infotrieve] Martins MD, Lozano-Chiu M, Rex JH. Declining rates of oropharyngeal candidiasis and carriage of Candida albicans associated with trends toward reduced rates of carriage of fluconazole-resistant C. albicansin human immunodeficiency virus-infected patients. Clin Infect Dis. 1998;27:1291-1291.[Web of Science][Medline] [Order article via Infotrieve] Arribas JR, Hernandez-Albujar S, Gonzalez-Garcia JJ, et al. Impact of protease inhibitor therapy on HIV-related oropharyngeal candidiasis. AIDS. 2000;14:979-985.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Pappas PG, Rex JH, Sobel JD, et al; Infectious Diseases Society of America. Guidelines for treatment of candidiasis. Clin Infect Dis. 2004;38:161-189.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Pons V, Greenspan D, Debruin M. Therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized, prospective, multicenter study of oral fluconazole vs. clotrimazole troches. J Acquir Immune Defic Syndr. 1993;6:1311-1316. Pons V, Greenspan D, Lorada-Nur F, et al. Oropharyngeal candidiasis in patients with AIDS: randomized comparison of fluconazole versus nystatin oral suspensions. Clin Infect Dis. 1997;24:1204-1207.[Web of Science][Medline] [Order article via Infotrieve] De Wit S, Weerts D, Goossens H, Clumeck N. Comparison of fluconazole and ketoconazole for oropharyngeal candidiasis in AIDS. Lancet. 1989;1:7468-7468. Smith DE, Midgley J, Allan M, et al. Itraconazole versus ketaconazole in the treatment of oral and oesophageal candidosis in patients infected with HIV. AIDS. 1991;5:1367-1371.[Web of Science][Medline] [Order article via Infotrieve] Laine L, Dretler RH, Conteas CN, et al. Fluconazole compared with ketoconazole for the treatment of Candidaesophagitis in AIDS: a randomized trial. Ann Intern Med. 1992;117:655-660. Barbaro G, Barbarini G, Di Lorenzo G. Fluconazole compared with itraconazole in the treatment of esophageal candidiasis in AIDS patients: a double-blind, randomized, controlled clinical study. Scand J Infect Dis. 1995;37:613-617. Mascarenas CA, Hardin TC, Pennick GJ, et al. Treatment of thrush with itraconazole solution: evidence for topical effect. Clin Infect Dis. 1998;26:12423-12423. Martins MD, Rex JH. Fluconazole suspension for oropharyngeal candidiasis unresponsive to tablets. Ann Intern Med. 1997;126:3323-3323. Ally R, Schurmann D, Kreisel W, et al. A randomized, doubleblind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients. Clin Infect Dis. 2001;33:1447-1454.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Hegener P, Troke PF, Fatkenheuer G, Diehl V, et al. Treatment of fluconazole-resistant candidiasis with voriconazole in patients with AIDS. AIDS. 1998;12:222-278.[Web of Science][Medline] [Order article via Infotrieve] Sobel JD, Brooker D, Stein GE, Thomason JL, et al. Single oral dose fluconazole comparedwith conventional clotrimazole topical therapy of Candida vaginitis. Fluconazole Vaginitis Study Group. Am J Obstet Gynecol. 1995;172(4 pt 1):1263-1268.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Powderly WG, Finkelstein D, Feinberg J, et al. A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. N Engl J Med. 1995;332:700-705. Schuman P, Capps L, Peng, et al. Weekly fluconazole for the prevention of mucosal candidiasis in women with HIV infection. Ann Intern Med. 1997;126:689-696. Powderly WG. Resistant candidiasis. AIDS Res Hum Retroviruses. 1994;10:925-929.[Web of Science][Medline] [Order article via Infotrieve] Maenza JR, Keruly JC, Moore RD, et al. Risk factors for fluconazole-resistant candidiasis in human immunodeficiency virus-infected patients. J Infect Dis. 1996;173:219-225.[Web of Science][Medline] [Order article via Infotrieve] Fichtenbaum CJ, Koletar S, Yiannoutsos C, et al. Refractory mucosal candidiasis in advanced human immunodeficiency virus infection. Clin Infect Dis. 2000;30:749-756.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Valdez H, Gripshover BM, Salata RA, Lederman MM. Resolution of azole-resistant oropharyngeal candidiasis after initiation of potent combination antiretroviral therapy. AIDS. 1998;12:538-538.[Web of Science][Medline] [Order article via Infotrieve] Phillips P, Zemcov J, Mahmood W, et al. Itraconazole cyclodextrin solution for fluconazole-refractory oropharyngeal candidiasis in AIDS: correlation of clinical response with in vitro susceptibility. AIDS. 1996;10:1369-1376.[Web of Science][Medline] [Order article via Infotrieve] Dentinger PJ, Swenson CF, Anaizi NH. Stability of amphotericin B in an extemporaneously compounded oral suspension. Am J Health Syst Pharm. 2001;58:1021-1024. Heinic GS, Stevens DA, Greenspan D, et al. Fluconazole-resistant Candidain AIDS patients: report of two cases. Oral Surg Oral Med Oral Pathol. 1993;76:711-715.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Quereda C, Polanco AM, Giner C, et al. Correlation between in vitro resistance to fluconazole and clinical outcome of oropharyngeal candidiasis in HIV-infected patients. Eur J Clin Microbiol Infect Dis. 1996;15:30-37.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Maenza JR, Merz WG, Romagnoli MJ, et al. Infection due to fluconazole-resistant Candidain patients with AIDS: prevalence and microbiology. Clin Infect Dis. 1997;24:28-34.[Web of Science][Medline] [Order article via Infotrieve] Laguna F, Rodriguez-Tudela JL, Martinez-Suarez JV, et al. Patterns of fluconazole susceptibility in isolates from human immunodeficiency virusinfected patients with oropharyngeal candidiasis due to Candida albicans. Clin Infect Dis. 1997;24:124-130.[Web of Science][Medline] [Order article via Infotrieve] Marichal P, Vanden Bossche H. Mechanisms of resistance to azole antifungals. Acta Biochimica Polonica 1995;42:509-516.[Web of Science][Medline] [Order article via Infotrieve] Arathoon EG, Gotuzzo E, Noriega LM, Berman RS, Di Nubile MJ, Sable CA. Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiasis. Antimicrob Agents Chemother. 2002;46:451-457. Villanueva A, Arathoon EG, Gotuzzo E, Berman RS, DiNubile MJ, Sable CA. A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis. Clin Infect Dis. 2001;33:1529-1535.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Villanueva A, Gotuzzo E, Arathoon E, et al. A randomized double-blind study of caspofungin versus fluconazole for the treatment of esophageal candidiasis. Am J Med. 2002;113:294-299.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Kartsonis N, DiNubile MJ, Bartizal K, Hicks PS, Ryan D, Sable CA. Efficacy of caspofungin in the treatment of esophageal candidiasis resistant to fluconazole. J Acquir Immune Defic Syndr Hum Retrovirol. 2002;31:183-187. Levits SM. The ecology of Cryptococcus neoformansand the epidemiology of cryptococcosis. Rev Infect Dis. 1991:13;1163-1169.[Web of Science][Medline] [Order article via Infotrieve] Pinner RW, Hajjeh RA, Powderly WG. Prospects for preventing cryptococcosis in persons infected with human immunodeficiency virus. Clin Infect Dis. 1995;21(suppl 1):S103-S107. Kwon-Chung KJ, Kozel TR, Edman JC, et al. Cryptococcosis. In: Medical Mycology. Philadelphia, Pa: Lea & Febiger; 1992:397-397. Brodt HR, Kamps BS, Gute P, et al. Changing incidence of AIDSdefining illnesses in the era of antiretroviral combination therapy. AIDS. 1997;11:1731-1738.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] French N, Gray K, Watera C, et al. Cryptococcal infection in a cohort of HIV-1-infected Ugandan adults. AIDS. 2002;16:1031-1038.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Desmet P, Kayembe KD, De Vroey C. The value of cryptococcal serum antigen screening among HIV-positive/AIDS patients in Kinshasa, Zaire. AIDS. 1989;3:77-78.[Web of Science][Medline] [Order article via Infotrieve] Concus AP, Helfand RF, Imber MJ, et al. Cutaneous cryptococcosismimicking molluscum contagiosum in a patient with AIDS. J Infect Dis. 1988;158:897-898.[Web of Science][Medline] [Order article via Infotrieve] Saag MS, Graybill RJ, Larsen RA, et al. Practice guidelines for the management of cryptococcal disease. Clin Infect Dis. 2000;30:710-718.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Van der Horst CM, Saag MS, Cloud GA, et al. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group. N Engl J Med. 1997;337:15-21. Saag MS, Cloud GA, Graybill R, NIAIDMycoses Study Group. A comparison of fluconazole versus itraconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1999;28:291-296.[Web of Science][Medline] [Order article via Infotrieve] Utz JP, Tynes JS, Shadomy HJ, et al. 5-fluorocytosine in human cryptococcosis. Antimicrob Agents Chemother. 1968;8:344-346.[Medline] [Order article via Infotrieve] Leenders AC, Reiss P, Portegies P, et al. Liposomal amphotericin B (Ambisome) compared with amphotericin B followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis. AIDS. 1997;11:1463-1471.[Web of Science][Medline] [Order article via Infotrieve] Bennett JE, Dismukes WE, Duma RJ, et al. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. N Engl J Med. 1979;301:126-131.[Abstract] Dismukes WE, Cloud G, Gallis H, et al. Treatment of cryptococcal meningitis with combination of amphotericin B and flucytosine for four as compared with six weeks. N Engl J Med. 1987;317:334-341.[Abstract] Larsen RA, Leal MA, Chan LS. Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS. Ann Intern Med. 1990;113:183-187. Saag MS, Powderly WG, Cloud GA, et al. Comparison of amphotericin Bwith fluconazole in the treatment of acute AIDSassociated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group. N Engl J Med. 1992;326:83-89.[Abstract] Larsen RA, Bozzette SA, Jones B, et al. Fluconazole combined with flucytosine for cryptococcal meningitis in persons with AIDS. Clin Infect Dis. 1994;19:741-745.[Web of Science][Medline] [Order article via Infotrieve] De Gans J, Portegies P, Tiessens G, et al. Itraconazole compared with amphotericin B plus flucytosine in AIDS patients with cryptococcal meningitis. AIDS. 1992;6:185-190.[Web of Science][Medline] [Order article via Infotrieve] Moskovitz BL, Wiesinger B, Cryptococcal meningitis Research Group. Randomized comparative trial of itraconazole and fluconazole for treatment of AIDS-related cryptococcal meningitis. In: Abstracts of the 1st National Conference on Human Retroviruses. Washington, DC: American Society for Microbiology; 1994:61-61. Coker RJ, Viviani M, Gazzard BG, et al. Treatment of cryptococcosis with liposomal amphotericin B (Am Bisome) in 23 patients with AIDS. AIDS. 1993;7:829-835.[Web of Science][Medline] [Order article via Infotrieve] Bozette SA, Larsen R, Chiu J, et al. A controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. NEngl J Med. 1991;324:580-584.[Abstract] Powderly WG, Saag MS, Cloud GA, et al. A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1992;326:793-798.[Abstract] Saag MS, Cloud GA, Graybill R, NIAIDMycoses Study Group. A comparison of fluconazole versus itraconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. Clin Infect Dis. 1999;28:291-296.[Web of Science][Medline] [Order article via Infotrieve] USPHS/IDSA Prevention of Opportunistic Infections Working Group. 2001 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. Available at: www.hivatis.org. Accessed April 4, 2005. Graybill JR, Sobel J, SaagM, et al. Cerebrospinal fluid hypertension patients with AIDS and cryptococcal meningitis. In: Program and Abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy (Toronto, ON, Canada). Washington, DC: American Society for Microbiology; 1997. Abstract I-153. Saag MS, Graybill RJ, Larsen RA, et al, for the Mycoses Study Group Cryptococcal Subproject. Practice guidelines for themanagement of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis. 2000;30:710-718.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Benson CA, Kaplan JE, Masur H, Pau A, Holmes KK. Centers for Disease Control and Prevention. National Institutes of Health. Infectious Diseases Society of America. Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. MMWR Morb Mortal Wkly Rep. 2004;53(RR-15):1-112.[Medline] [Order article via Infotrieve] Williams B, Fojtase kM, Connolly-Stringfield P, Wheat J. Diagnosis of histoplasmosis by antigen detection during an outbreak in Indianapolis, Ind. Arch Pathol Lab Med. 1994;118:1205-1208.[Web of Science][Medline] [Order article via Infotrieve] Johnson PC, Wheat LJ, Cloud GA, et al. Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS. Ann Intern Med. 2002;137:105-109. Hecht FM, Wheat J, Korzun AH, et al. Itraconazole maintenance treatment for histoplasmosis in AIDS: a prospective, multicenter trial. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;16:100-107.[Web of Science][Medline] [Order article via Infotrieve] Sarosi GA, Johnson PC. Disseminated histoplasmosis in patients infected with human immunodeficiency virus. Clin Infect Dis. 1992;14(suppl 1):S60-S67. Wheat LJ, Connolly-Stringfield PA, Baker RL, et al. Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature. Medicine. 1990;69:361-374.[Medline] [Order article via Infotrieve] Wheat J, Hafner R, Wulfsohn M, et al. The National Institute of Allergy and Infectious Diseases Clinical Trials and Mycoses Study Group Collaborators. Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1993;118:610-616. McKinsey DS, Gupta MR, Driks MR, et al. Histoplasmosis in patients with AIDS: efficacy of maintenance amphotericin B therapy. Am J Med. 1992;92:225-227.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Wheat J, MaWhinney S, Hafner R, et al. National Institute of Allergy and Infectious Diseases Acquired Immunodeficiency Syndrome Clinical Trials Group and Mycoses Study Group. Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome. Am J Med. 1997;103:223-232.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Norris S, Wheat J, McKinsey D, et al. Prevention of relapse of histoplasmosis with fluconazole in patients with the acquired immunodeficiency syndrome. Am J Med. 1994;96:504-508.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Wheat J, Sarosi G, McKinsey D, et al. Practice guidelines for the management of patients with histoplasmosis. Infectious Diseases Society of America. Clin Infect Dis. 2000;30:688-695.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Wheat J, Hafner R, Korzun AH, et al. Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trial Group. Am J Med. 1995;98:336-342.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Barone JA, Koh JG, Bierman RH, et al. Food interaction and steady-state pharmacokinetics of itraconazole capsules in healthy male volunteers. Antimicrob Agents Chemother. 1993;37:778-784. Sporanox [package insert]. Titusville, NJ: Janssen; 2001. Ruhnke M, Schmidt-Westhausen A, Trautmann M. In vitro activities of voriconazole (UK-109,496) against fluconazole-susceptible and resistant Candida albicansisolates from oral cavities of patients with human immunodeficiency virus infection. Antimicrob Agents Chemother. 1997;41:575-577. Boucher HW, Groll AH, Chiou CC, Walsh TJ. Newer systemic antifungal agents: pharmacokinetics, safety and efficacy. Drugs. 2004;64:1997-2020.[CrossRef][Web of Science][Medline] [Order article via Infotrieve] Sharkey PK, Graybill JR, Johnson ES, et al. Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1996;22:315-321.[Web of Science][Medline] [Order article via Infotrieve] Abelcet [package insert]. San Diego, Calif: Elan Pharmaceuticals; 2002. Ambisome [package insert]. San Dimas, Calif: Gilead Sciences; 2002. Cancidas [package insert]. Whitehouse Station, NJ: Merck & Co; 2004.
Journal of Pharmacy Practice, Vol. 19, No. 1,
17-30 (2006)
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