What is the mechanism of action of the drug used to treat a patient with Human Immunodeficiency Virus (HIV) presenting with oral candidiasis, who is currently on Azithromycin (azithromycin), with a viral load of 17,000 and a CD4 count of 120?

From the Guidelines

The patient should be treated with fluconazole, which works by inhibiting ergosterol synthesis in the fungal cell membrane, as it is the most effective treatment for oral candidiasis in HIV patients with low CD4 counts, according to the most recent and highest quality study 1. The patient is presenting with oral candidiasis (thrush), which is a common opportunistic infection in HIV patients with low CD4 counts (below 200, in this case 120).

• The appropriate treatment would be an antifungal medication like fluconazole,
• which works by inhibiting ergosterol synthesis in the fungal cell membrane.
• Ergosterol is essential for maintaining cell membrane integrity in fungi,
• and its disruption leads to increased permeability, leakage of cellular contents, and ultimately cell death. This mechanism is specific to azole antifungals,
• which target the cytochrome P450-dependent enzyme lanosterol 14-alpha-demethylase,
• preventing the conversion of lanosterol to ergosterol. The patient's high viral load and low CD4 count indicate advanced HIV infection requiring both treatment of the opportunistic infection and initiation of antiretroviral therapy to improve immune function, as recommended by 1 and 1.
• The use of HAART has been associated with decreasing rates of oral carriage of Candida species and reduced frequency of symptomatic oropharyngeal candidiasis, as noted in 1.
• Therefore, initiation of antiretroviral therapy is crucial in managing the patient's condition, in addition to treating the oral candidiasis with fluconazole, as supported by 1.
• It is also important to note that fluconazole-refractory infections can be treated with itraconazole solution or posaconazole suspension, as recommended by 1 and 1. However, fluconazole remains the first-line treatment for oral candidiasis in HIV patients, due to its efficacy and safety profile, as established by 1.

From the FDA Drug Label

1. 4 Microbiology Mechanism of Action Voriconazole is an azole antifungal drug. The primary mode of action of voriconazole is the inhibition of fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylation, an essential step in fungal ergosterol biosynthesis

• The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell wall and may be responsible for the antifungal activity of voriconazole.

The mechanism of action of the drug used to treat a patient with Human Immunodeficiency Virus (HIV) presenting with oral candidiasis is inhibition of fungal cytochrome P-450-mediated 14 alpha-lanosterol demethylation. This is the primary mode of action of voriconazole, an azole antifungal drug 2.

From the Research

Mechanism of Action of Antifungal Drugs

The patient with Human Immunodeficiency Virus (HIV) presenting with oral candidiasis is likely to be treated with antifungal drugs. The mechanism of action of these drugs varies:

• Polyenes (nystatin, amphotericin B) work by binding to ergosterol in the fungal cell membrane, creating pores that allow ions to escape, leading to cell death 3.
• Azoles (ketoconazole, miconazole, clotrimazole, fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole) inhibit the synthesis of ergosterol, a critical component of the fungal cell membrane, by blocking the enzyme lanosterol 14α-demethylase 3.
• Echinocandins (caspofungin, micafungin, anidulafungin) inhibit the synthesis of β-glucan, a key component of the fungal cell wall, by blocking the enzyme glucan synthase 3.

Treatment Options for Oral Candidiasis

The treatment options for oral candidiasis in HIV-infected patients include:

• Topical antifungal agents such as nystatin, miconazole, and clotrimazole 4, 3.
• Systemic antifungal agents such as fluconazole, itraconazole, and posaconazole 5, 6.
• Echinocandins (caspofungin, micafungin, and anidulafungin) can be used as alternative agents in patients with fluconazole-refractory mucosal candidiasis 6.

Considerations for Treatment

When treating oral candidiasis in HIV-infected patients, it is essential to consider the degree of immunosuppression, as relapse is more common in patients with lower CD4 counts 6. Additionally, the potential for drug interactions and resistance should be taken into account, particularly when using azole antifungals 5, 7. The patient's current medication, azithromycin, should also be considered when selecting an antifungal agent to avoid potential interactions.