When Common Antifungals Stop Working
Rising Drug Resistance in Oral Candidiasis Among People Living with HIV
A Persistent Oral Infection in HIV
Oral candidiasis often known as oral thrush is one of the most common opportunistic infections affecting people living with HIV. Caused by Candida fungi, this condition can appear as white patches, redness, or painful lesions in the mouth. Beyond discomfort, oral candidiasis is often an early warning sign of immune suppression and may signal progression of HIV disease.
For years, antifungal drugs especially azoles such as fluconazole have been the mainstay of treatment. However, clinicians around the world are now facing a growing challenge: these once-reliable medications are increasingly failing to work.
Why Drug Resistance Matters
Repeated or prolonged use of antifungal drugs, particularly in recurrent infections, can allow Candida species to adapt and develop resistance. This problem is compounded by the rise of non-albicans Candida species, which are naturally more resistant to common treatments.
Drug-resistant oral candidiasis does not just mean longer treatment it can lead to repeated infections, higher healthcare costs, and in severe cases, progression to systemic fungal disease.
What Did the Researchers Do?
To better understand the scale of this problem, Keyvanfar and colleagues conducted a systematic review and meta-analysis, published in BMC Infectious Diseases in 2024.
The researchers analyzed data from:
25 observational studies
2,564 Candida isolates
Studies published between 2000 and November 2023
Multiple regions worldwide, including Africa, Asia, and South America
They focused on how often Candida species isolated from HIV-positive patients with oral candidiasis were resistant to commonly used antifungal drugs.
Key Findings: Azoles Under Pressure
The analysis revealed a concerning pattern. Resistance was highest among azole antifungals, which are frequently used as first-line therapy:
Ketoconazole: 25.5% resistance
Fluconazole: 24.8%
Itraconazole & Voriconazole: ~20%
Clotrimazole & Miconazole: 13–15%
Resistance to 5-flucytosine was also notable, though results varied widely between studies.
In contrast, polyenes and echinocandins remained highly effective:
Nystatin: >95% of isolates remained susceptible
Amphotericin B: ~97% susceptibility
Caspofungin: nearly 100% susceptibility, with virtually no resistance reported
These findings suggest that while azoles are still widely prescribed, their effectiveness is steadily eroding in this patient population.
What Does This Mean for Clinical Practice?
The study sends a clear message: empirical use of azoles may no longer be sufficient, especially in recurrent or treatment-resistant cases of oral candidiasis in people living with HIV.
Clinicians may need to:
Consider antifungal susceptibility testing more routinely
Use alternative treatments such as nystatin or amphotericin B when azole resistance is suspected
Reserve caspofungin for refractory or severe cases, despite its intravenous administration
Looking Ahead
This meta-analysis is one of the most comprehensive evaluations to date on antifungal resistance in HIV-associated oral candidiasis. It highlights an urgent need for more targeted treatment strategies and greater awareness of resistance patterns.
As HIV care continues to improve and patients live longer, managing opportunistic infections effectively including knowing when standard therapies may fail will remain a critical part of comprehensive HIV care.
Reference (Original Article)
Keyvanfar, A., Najafiarab, H., Talebian, N., et al. (2024).
Drug-resistant oral candidiasis in patients with HIV infection: a systematic review and meta-analysis.
BMC Infectious Diseases, 24, 546.
DOI: https://doi.org/10.1186/s12879-024-09442-6