Abstract
BACKGROUND
Visceral leishmaniasis (VL) in patients living with Human-Immunodeficiency-Virus (HIV) present an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian sub-continent.
METHODS
This is a randomised open label, parallel arm phase-3 trial conducted within a single hospital in Patna, India. 150 patients aged =18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to one of two treatment arms, either a total 40mg/kg intravenous liposomal amphotericin B(AmBisome) administered in 8 equal doses over 24-days, or a total 30mg/kg intravenous liposomal amphotericin B(AmBisome) administered in 6 equal doses given concomitantly with a total 1.4g oral miltefosine administered through two daily doses of 50mg over 14-days. The primary outcome was ITT relapse-free-survival at day-210, defined as absence of signs and symptoms of VL, or if symptomatic negative parasitological investigations.
FINDINGS
Among 243 patients assessed for eligibility, 150 were recruited between 2nd January 2017 and 5th April 2018, with no loss-to-follow-up. Relapse free survival at day-210 was 85%, (64/75; 95%CI 77-100) in the monotherapy arm, and 96%, (72/75;95%CI 90-100) in the combination arm. 19%(28/150) were infected with concurrent tuberculosis, divided equally between arms. Excluding those with concurrent tuberculosis, relapse free survival at day-210 was 90%, (55/61;95%CI 82-100) in the monotherapy and 97%, (59/61;95%CI 91-100) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm.
CONCLUSIONS
Combination therapy appears to be safe, well tolerated and effective, and halves treatment duration of current recommendations.
