Oral amphotericin B may be effective in HIV-associated cryptococcal meningitis

Oral lipid nanocrystal (LNC) amphotericin B has similar efficacy to intravenous (IV) amphotericin in patients with HIV-associated cryptococcal meningitis, according to study results were published in Clinical Infectious Diseases.

In this open-label, phase 2, randomized clinical trial, researchers compared the antifungal efficacy of oral LNC amphotericin B (intervention) against IV amphotericin (control) for the treatment of HIV-associated cryptococcal meningitis across 4 sequential cohorts (n=141). For each cohort, eligible patients (N=141) were randomly assigned 2:5:1 to either interventional or control arms. Patients in the control arms were pooled across the 4 cohorts and considered a single control cohort. Patients in the intervention cohorts received oral LNC amphotericin plus flucytosine with (n=40) or without (n=40) 2 IV loading doses of amphotericin, and those in the control cohort (n=41) received IV amphotericin plus flucytosine.

The trial was conducted between July 2020 and October 2022, with a follow-up period of 18 weeks. The primary endpoint was rate of early fungicidal activity (EFA) of cerebrospinal fluid (CSF) Cryptococcus clearance, defined as the change in log₁₀ Cryptococcus colony-forming units (CFU)/mL in CSF daily as measured via serial quantitative CSF fungal cultures over a period of approximately 2 weeks. The researchers fit a simple linear regression model for each patient.

Among patients included in the analysis, the median age was 36 (IQR, 31-42) years, 50% were women, 67% were naive to antiretroviral therapy, the median CD4 count was 30 (IQR, 10-85) cells/µL, and the median CSF quantitative culture was 6600 Cryptococcus CFU/mL. Of note, 85% of patients had nonsterile CSF at baseline.

At 18 weeks, the rate of survival was higher among patients in the oral arm who received IV loading doses (90%) compared with those who received only oral treatment and those in the control cohort (both 85%). Patients who received oral LNC amphotericin B achieved CSF sterility after 2 weeks at similar rates to those in the control cohort (63% vs 68%, respectively).

There was no significant difference observed between patients in the intervention cohorts in regard to the primary endpoint. For patients who received only oral LNC amphotericin B and those who received oral treatment plus an IV loading dose, the mean EFA was 0.40 and 0.46 log₁₀ CFU/mL daily, respectively.

Limitations of the study include the inability to determine the relative effectiveness between amphotericin and flucytosine.

According to the researchers “If LNC amphotericin with flucytosine can treat a 100% fatal fungal infection of the brain in severely immunocompromised persons with HIV, treatment of other fungal infections should be possible.”

Disclosure: This research was supported by Matinas BioPharma, and multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

By Janelle Barowski, MSN RN

References:

Boulware DR, Atukunda M, Kagimu E, et al. Oral lipid nanocrystal amphotericin B for cryptococcal meningitis: a randomized clinical trial. Clin Infect Dis. Published online August 22, 2023. doi:10.1093/cid/ciad440