Antifungals Used to Treat HIV-Related Infections

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Systemic fungal infections continue to be a major cause of illness and death in people with HIV, while superficial or uncomplicated infections are commonly noted. Among the opportunistic fungal infections most frequently associated with HIV:

A number of other fungal infections (including aspergillosis, penicillosis, and blastomycosis) have also been noted, most often in individuals with CD4 counts below 250 cells/mL.

There are a number of agents commonly used to treat HIV-related fungal infections. The drugs are categorized by their specific mechanism of action, and can be broken down into four general groups:

I. Polyene Antifungals

Polyene antifungals work by breaking down the integrity of the fungal cell membrane, which eventually leads to cell death. The most common polyene antifungals used in HIV are:

  • Amphotericin B: Commonly associated with the treatment of systemic (whole body) fungal infections such as cryptococcal meningitis. When administered intravenously, amphotericin B is known to have serious potential side effects, often with acute reaction occurring shortly after infusion (e.g., fever, chills, rigor, nausea, vomiting, headache, and muscle/joint pain). As such, intravenous administration of amphotericin B is generally indicated in severely immune-compromised or critically ill patients. Oral preparations are available for use in treating candidiasis, which are safe for use with low drug toxicity.
  • Nystatin: Administered either orally or topically for superficial oral, esophageal, and vaginal candidiasis. Nystatin can also be used as a prophylactic (preventative) therapy in HIV-infected patients with high risk for fungal infection (CD4 count of 100 cells/mL or less). Nystatin is available as tablets, mouthwash, pastilles, powders, creams, and ointments.​

    II. Azole Antifungals

    Azole antifungals interrupt the synthesis of enzymes needed to maintain the integrity of the fungal membrane, thereby inhibiting the fungus' ability to grow. Common side effects include rash, headache, dizziness, nausea, vomiting, diarrhea, stomach cramps, and elevated liver enzymes.

    • Diflucan (fluconazole): Arguably one of the most prescribed antifungals worldwide, Diflucan is used for the treatment of superficial and systemic fungal infections, including candidiasis, cryptococcosis, histoplasmosis, and coccidioidomycosis. Diflucan is available in tablet form, as a powder for oral suspension, or as a sterile solution for intravenous use.
    • Nizoral (ketoconazole): Nizoral was the very first oral azole antifungal medication, but has largely been supplanted by other azoles that have less toxicity and far greater absorption. It is available in tablet form, as well as in various topical applications for use on superficial fungal infections, including candidiasis.
    • Sporanox (itraconazole): Commonly used in systemic infection (such as candidiasis or cryptococcosis) when other antifungals are either ineffective or inappropriate. Sporanox is available in capsule form or as an oral solution (considered superior in terms of absorption and bioavailability). The intravenous preparation is no longer available in the U.S. Because of its low penetration into the cerebrospinal fluid, Sporanox is generally used only in second line when treating cryptococcal meningitis.

      Other azoles being used in the treatment of opportunistic fungal infections are VFend (voriconazole) and Posanol (posaconazole).

      III. Antimetabolite Antifungal

      There is only one antimetabolite drug (Ancobon) known to have antifungal properties, which it accomplishes by interfering with both RNA and DNA synthesis.

      • Ancobon (flucytosine): Used for treating serious cases of candidiasis and cryptococcosis, Ancobon is always administered with fluconazole and/or amphotericin B as the development of resistance is common when used alone. The combination of amphotericin B and Ancobon has proven to be favorable in the treatment of cryptococcal meningitis. Ancobon is available in capsule form. Side effects can include gastrointestinal intolerance and bone marrow suppression (including anemia). Rash, headache, confusion, hallucination, sedation, and elevated liver function have also been reported.

      IV. Echinocandins

      A newer class of antifungals called echinocandins are also being employed in the treatment of candidiasis and aspergillosis. Echinocandins work by inhibiting the synthesis of certain polysaccharides in the fungal cell wall. Generally speaking, echinocandins offer lower toxicity and fewer drug-drug interactions, although at present they are more often prescribed in patients with intolerance to other traditional antifungal medications. All three are administered intravenously, with similar safety, efficacy, and tolerability.

      • Eraxis (anidulafungin)
      • Cancidas (caspofungin)
      • Mycamine (micafungin)


      Marty, F. and Mylonakis, E. "Antifungal use in HIV infection." Expert Opinion Pharmacotherapy. February, 2002; 3(2):91-102.

      Mei, H.; Kok, L.; Shariff, M.; et al. "Antifungal Use for Opportunistic Infection in HIV Patients: Comparison of Efficacy and Safety." WebmedCentral AIDS. 2011; 2(12):WMC002674.

      National Institutes of Health (NIH). "Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents." Bethesda, Maryland; updated September 27, 2013.

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