AmBisome Monotheraphy and Combination AmBisome Miltefosine Therapy for the Treatment of Visceral Leishmaniasis in Patients Coinfected with Human Immunodeficiency Virus in India A Randomized Open Label Parallel Arm Phase 3 Trial

Bihar has nearly 40 percent of global Visceral Leishmaniasis (VL) burden. In addition, Bihar is one of the few states in India where rate of new Human Immunodeficiency Virus (HIV) infections is increasing, led to major implications for VL-HIV coinfection. This study used parallel-arm open-label, randomised noncomparative phase 3 trials to investigate the safety and efficacy of two treatment regimens for Visceral Leishmaniasis inpatients co-infected with HIV in Bihar, India. Also, a sub-group analysis restricted to those without TB at time of enrolment was done as secondary objective. This study included patients with aged 18 years and above with a confirmed diagnosis of HIV with a parasitologically confirmed diagnosis of VL. A total of 150 patients were selected and randomly allocated to two treatment arms. A total of 75 patients were given liposomal Amphotericin B (Treatment Arm 1) with a total dose of 40mg/kg. On the other hand, 75 patients were allocated to treatment (treatment arm 2) where combination therapy was administered with a total dose of 30mg/kg Ambisome and a total dose of 1.4 gram of miltefosine (administered as one 50 mg capsule twice a day for 14 days). During treatment, patients were assessed as inpatients on days 1, 3, 10, 14 and 29 days. Following discharge patients were assessed on day 58 (±10 days), day 210 (±1 months) and day 390 (±2 months). Results showed relapse-free survival at day 210 was 85% (64/75; 95% CI, 77–100%) in the monotherapy arm, and 96%, (72/75; 90–100%) in the combination arm. 19% (28/150) were infected with concurrent tuberculosis. Excluding those with concurrent tuberculosis, relapse-free survival at day 210 was 90% (55/61; 82–100%) in the monotherapy and 97% (59/61; 91–100%) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm. Combination therapy appears to be safe, well tolerated, and effective, and halves treatment duration of current recommendations.