Abstract
BackgroundVisceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. AmBisome monotherapy at 40 mg/kg is recommended by the World Health Organization. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment.Methodology/Principal findingsAn open-label, non-comparative randomized trial of AmBisome (30 mg/kg) with miltefosine (100 mg/day for 28 days), and AmBisome monotherapy (40 mg/kg) was conducted in Ethiopian VL patients co-infected with HIV (NCT02011958). A sequential design was used with a triangular continuation region. The primary outcome was parasite clearance at day 29, after the first round of treatment. Patients with clinical improvement but without parasite clearance at day 29 received a second round of the allocated treatment. Efficacy was evaluated again at day 58, after completion of treatment.Recruitment was stopped after inclusion of 19 and 39 patients in monotherapy and combination arms respectively, as per pre-specified stopping rules. At D29, intention-to-treat efficacy in the AmBisome arm was 70% (95% CI 45–87%) in the unadjusted analysis, and 50% (95% CI 27–73%) in the adjusted analysis, while in the combination arm, it was 81% (95% CI 67–90%) and 67% (95% CI 48–82%) respectively. At D58, the adjusted efficacy was 55% (95% CI 32–78%) in the monotherapy arm, and 88% (95% CI 79–98%) in the combination arm.No major safety concerns related to the study medication were identified. Ten SAEs were observed within the treatment period, and 4 deaths unrelated to the study medication.Conclusions/SignificanceThe extended treatment strategy with the combination regimen showed the highest documented efficacy in HIV-VL patients; these results support a recommendation of this regimen as first-line treatment strategy for HIV-VL patients in eastern Africa.Trial registration numberwww.clinicaltrials.gov NCT02011958.
Highlights
Human immunodeficiency virus (HIV) affects visceral leishmaniasis (VL) by increasing its incidence, altering its clinical manifestation and severity, and, more importantly, by worsening treatment outcomes and relapse rates [1,2]
Visceral Leishmaniasis is a complex parasitological disease and is challenging to treat in patients coinfected with human immunodeficiency virus (HIV)
In 2010, a WHO expert committee recommended a lipid formulation of amphotericin B as first line treatment for HIV/Visceral leishmaniasis (VL) coinfected patients, based on a single clinical trial conducted in Spain and empirical information obtained from scattered case reports using AmBisome
Summary
Human immunodeficiency virus (HIV) affects visceral leishmaniasis (VL) by increasing its incidence, altering its clinical manifestation and severity, and, more importantly, by worsening treatment outcomes and relapse rates [1,2]. HIV-VL co-infection has been observed in at least 35 countries on four continents [3,4,5,6]. Following the introduction of highly active anti-retroviral therapy (HAART), the incidence of VL in HIV patients has decreased in most settings [7]. Northwest Ethiopia has the highest burden globally, with HIV rates among VL patients ranging between 20–40% [2,3]. Migrant workers are at high risk of HIV infection [2,8,9]. Visceral leishmaniasis (VL) in human immunodeficiency virus (HIV) co-infected patients requires special case management. The objective of the study was to assess if a combination of a lower dose of AmBisome with miltefosine would show acceptable efficacy at the end of treatment
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