Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. This randomized clinical trial found that an oral lipid nanocrystal (LNC) formulation of amphotericin B was no less effective in the treatment of cryptococcal meningitis in patient cohorts with Human Immunodeficiency Virus (HIV). Early fungicidal activity in the cerebrospinal fluid was comparable among both experimental and control groups.

2. LNC also demonstrated higher tolerability compared to intravenous (IV) amphotericin, as well as a comparable safety profile.

Evidence Rating Level: 1 (Excellent)

HIV and acquired immune deficiency syndrome (AIDS) predisposes sufferers to opportunistic infections. Among the most common of these is a fungal infection, cryptococcal meningitis. Although over 50 species of cryptococcus exist, C. neoformans, a yeast found in pigeon droppings, and C. gattii, cause the majority of infections in humans. Without treatment, cryptococcal meningitis is fatal. Intravenous (IV) Amphotericin B has long been the gold standard of treatment, however, a new oral formulation of amphotericin has recently been developed. The current randomized clinical trial tested oral lipid nanocrystal (LNC) amphotericin B (MAT2203, Matinas Biopharma) to assess its comparable safety, tolerability, and efficacy compared to the gold standard. Arm 1 received oral LNC + flucytosine with (n = 40) or without (n = 40) 2 IV loading doses, and controls received IV amphotericin + flucytosine (n = 41). Cerebrospinal fluid early fungicidal activity (CSF EFA; CSF cryptococcus clearance rate) was not statistically significantly different between the LNC and IV amphotericin regimens. Rates of 18-week survival were 85% in both the IV amphotericin group and all-oral LNC amphotericin, and 90% in the LNC amphotericin with 2 IV loading doses. There was a decrease of 4.6% in absolute risk difference in mortality for the LNC + 2 IV loading doses group (95% CI: −18.9% to 9.6%). The tolerability of LNC was excellent, and toxicities were significantly reduced in the LNC group compared to the IV amphotericin control group. Clinical AEs (41% LNC amphotericin vs. 56% controls) and serious AEs (26% LNC amphotericin vs. 27% controls) were the same among the control and experimental groups. In controls, potassium AEs occurred more than three times as often (p = .04), new onset anemia occurred more than nine times more frequently, mild nephrotoxicity within 6 weeks occurred twice more often than the LNC + 2 IV loading dose group, and four times more often than the LNC oral only group. Overall, these results indicate that antifungal activity in CSF was similar among both the oral and IV groups, all while maintaining a sound safety and tolerability profile. Future studies should explore the administration of LNC in other opportunistic fungal infections, which could result in tangible benefits and reductions in mortality among the immunocompromised.

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