Antifungals Used to Treat HIV-Related Infections

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:

  • Candidiasis
  • Cryptococcosis (including cryptococcal meningitis)
  • Histoplasmosis
  • Coccidioidomycosis (Valley Fever)

A number of other fungal infections (including aspergillosis, penicillosis, and blastomycosis) are also common in later-stage disease, most often in people with CD4 counts below 250.

There are a number of drugs 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: polyene antifungals, azole antifungals, antimetabolite antifungals, and echinocandins.

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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

Amphotericin B is commonly used for the treatment of systemic (whole-body) fungal infections such as cryptococcal meningitis. When delivered intravenously, amphotericin B is known to have serious side effects, often with an acute reaction occurring shortly after infusion (e.g., fever, chills, rigor, nausea, vomiting, headache, and muscle/joint pain). As such, the 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 is safe for use with low drug toxicity.


Nystatin is delivered 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.

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)

Diflucan (fluconazole) is 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 (ketoconazole) 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)

Sporanox (itraconazole) is 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 treatment when treating cryptococcal meningitis.

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

Antimetabolite Antifungal

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

Ancobon is used for treating serious cases of candidiasis and cryptococcosis. It 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.


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 used in people with intolerance to other traditional antifungals. All three are administered intravenously have similar safety, efficacy, and tolerability.

The three approved by the U.S. Food and Drug Administration (FDA) are:

  • Eraxis (anidulafungin)
  • Cancidas (caspofungin)
  • Mycamine (micafungin)
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By James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.