A randomized trial of AmBisome monotherapy and AmBisome and miltefosine combination to treat visceral leishmaniasis in HIV co-infected patients in Ethiopia

摘要

Author summary Visceral Leishmaniasis is a complex parasitological disease and is particularly challenging to treat in patients coinfected with human immunodeficiency virus (HIV). Antimonial drugs used in first-line treatments for immunocompetent patients in eastern Africa are more toxic in immunocompromised patients. In 2010, a WHO expert committee recommended a lipid formulation of amphotericin B as first line treatment for HIV/VL co-infected patients, based on a single clinical trial conducted in Spain and empirical information obtained from scattered case reports using AmBisome (liposomal amphotericin B). In addition, Mdecins Sans Frontires began a compassionate use regimen combining AmBisome and miltefosine a in a treatment centre in Northwest Ethiopia with encouraging results. Here, we report the results of a trial to assess the efficacy and safety of both the currently internationally recommended treatment of AmBisome monotherapy and the new AmBisome-miltefosine combination regimen, in Ethiopian patients. The results of this trial show that one course of treatment with either regimen could be insufficient to clear parasites in a high proportion of patients and that an extended treatment strategy, of administrating a second course of treatment, could lead to a high parasite clearance rate in patients treated with the combination regimen.