Single high-dose liposomal amphotericin B (L-AmB) is non-inferior to daily dosed L-AmB at the standard dose in treatment of fungal clearance in HIV-associated cryptococcal meningitis (CM), according to findings published in Clinical Infectious Diseases.
Several national guidelines recommend L-AmB as treatment for HIV-associated CM but the optimal regimen has not been well defined. The use of a short course of high-dose L-AmB for HIV-associated CM has also not been previously evaluated in a clinical trial. In this study, the investigators conducted an open label phase 2 randomized non-inferiority trial to evaluate alternative regimens of L-AmB. A cohort of 80 HIV-positive individuals with CM were randomly assigned to either L-AmB 10mg/kg day 1 (single dose); L-AmB 10mg/kg day 1, 5mg/kg day 3 (3 doses); L-AmB 10mg/kg day 1, 5 mg/kg days 3 and 7 (3 doses); or standard 14-day L-AmB 3mg/kg/day (control). All regimens were given with fluconazole.
The study’s primary end point was the mean rate of cryptococal infection (EFA) from the cerebrospinal fluid. The difference in mean EFA vs control was −0.11 (95% CI, −0.29,0.07) log10CFU/mL/day faster for the single dose (n=16), −0.05 (95% CI, −0.20,0.10) log10CFU/mL/day faster with 2 doses (n=18), and −0.13 (95% CI, −0.35,0.09) log10CFU/mL/day faster with the 3-dose regimen (n=18). The EFA for all short-course cohorts was non-inferior to the control group at the pre-defined non-inferiority margin. At 10 weeks, the overall mortality was 29% (n=23), and there were no statistical differences between the groups.
“Reductions in the need for toxicity monitoring, fewer drug related adverse events, and the potential for shorter periods of hospitalization are likely to mean that a single high-dose L-AmB treatment strategy is cost effective, and a highly favorable alternative to the current standard of care,” the investigators concluded.
Jarvis JN, Leeme TB, Molefi M, et al. Short course high-dose liposomal amphotericin B for HIV-associated cryptococcal meningitis: a phase-II randomized controlled trial [published online June 26, 2018]. Clin Infect Dis. doi:10.1093/cid/ciy515