• Gakuru, Jane
• Musubire, Abdu
• Nsangi, Laura
• Tugume, Lillian
• Meya, David
• Rutakingirwa, Morris K.
• Kagimu, Enock
• Atukunda, Mucunguzi
• Williams, Darlisha A.
• Mpoza, Edward
• Ellis, Jayne
• Kasibante, John
• Boulware, David R.
• Hullsiek, Kathy Huppler
• Ssebambulidde, Kenneth
• Abassi, Mahsa
• Akampurira, Andrew
• Skipper, Caleb
• Fieberg, Ann M.
• Mugabi, Timothy

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Intravenous (IV) amphotericin B is the gold standard treatment of severe mycoses. A new orally absorbed, less-toxic formulation of amphotericin has been developed (Matinas Biopharma). We evaluated the efficacy of this novel anti-fungal agent amongst adults with cryptococcal meningitis.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted a phase II randomized clinical trial testing oral encochleated amphotericin B (cAMB) versus IV amphotericin B for first episode cryptococcal meningitis in Kampala, Uganda from December 2020 to August 2021. Participants were HIV-positive, CSF cryptococcal antigen (CrAg) positive, and had the capacity to consent and take oral medications (GCS=15). Participants in the experimental arm received two loading doses of either IV deoxycholate amphotericin B 1.0 mg/kg/day or liposomal amphotericin 3 mg/kg/day, followed by 1.8g oral cAMB daily in 6 divided doses through 2 weeks with flucytosine (5FC) at 100mg/kg/day, and thereafter cAMB at 1.2g daily in 4 divided doses through 6 weeks. Participants in the control arm received 7 days of IV amphotericin B (deoxycholate or liposomal) with 5FC, then 7 days of fluconazole 1200mg/day. After 14 days, all participants received fluconazole 800mg/day through 10 weeks and thereafter a maintenance dose of 200mg/day.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We randomized 40 participants to oral cAMB + 5FC and 30 control participants to IV amphotericin + 5FC. With cAMB the 30-day survival was 97.5% (39/40) and 18-week survival was 90% (36/40) compared with 87% (26/30) 18-week survival in IV amphotericin controls.</jats:p><jats:p>The CSF Early Fungicidal Activity (EFA) was lower with oral cAMB (mean EFA = 0.42 log10Cryptococcus CFU/mL/day; 95%CI, 0.29 to 0.54) versus IV amphotericin (mean EFA = 0.52 log10 CFU/mL/day; 95%CI, 0.39 to 0.66). Among those CSF culture positive at baseline, CSF sterility was achieved by 2 weeks in 65% (24/37) of cAMB participants and 68% (17/25) of controls.</jats:p><jats:p>Grade &amp;gt;=3 laboratory adverse events were more common with IV amphotericin. Grade 3–4 anaemia occurred in 10% (n=4) with cAMB versus 37% (n=11) with IV amphotericin. Grade 3 hypokalaemia (&amp;lt; 3mEq/L) occurred in 5% (n=2) with cAMB versus 27% (n=8) with IV amphotericin.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Novel oral cAMB appears to be a safe agent with promising efficacy for HIV-related cryptococcal meningitis.</jats:p></jats:sec><jats:sec><jats:title>Disclosures</jats:title><jats:p>All Authors: No reported disclosures.</jats:p></jats:sec>

Topics

• impedance spectroscopy
• phase
• laser emission spectroscopy
• gold
• size-exclusion chromatography
• gas chromatography
• chemical ionisation