AmBisome Monotherapy 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 . (11th February 2022)

• Record Type: Journal Article
• Authors: Burza, Sakib; Mahajan, Raman; Kazmi, Shahwar; Alexander, Neal; Kumar, Deepak; Kumar, Vikash; Lasry, Estrella; Harshana, Amit; de Lima Pereira, Alan; Das, Pradeep; Verma, Neena; Das, Vidya Nand Ravi; Lal, Chandra Shekhar; Rewari, Bharat; Goyal, Vishal; Rijal, Suman; Alves, Fabiana; Gill, Naresh; Pandey, Krishna
• Is Part Of: Clinical infectious diseases. Volume 75:Number 8(2022)
• Page Start: 1423
• Page End: 1432
• Publication Date: 2022-02-11
• Subjects: visceral leishmaniasis -- liposomal amphotericin B -- HIV -- miltefosine -- India; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciac127
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: Visceral leishmaniasis (VL) in patients with human immunodeficiency virus (HIV) presents 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 subcontinent. Methods: This is a randomized, open-label, parallel-arm, phase 3 trial conducted within a single hospital in Patna, India. One hundred and fifty patients aged ≥18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to 1 of 2 treatment arms, either a total 40 mg/kg intravenous liposomal amphotericin B (AmBisome; Gilead Pharmaceuticals) administered in 8 equal doses over 24 days or a total 30 mg/kg intravenous AmBisome administered in 6 equal doses given concomitantly with a total 1.4 g oral miltefosine administered through 2 daily doses of 50 mg over 14 days. The primary outcome was intention-to-treat relapse-free survival at day 210, defined as absence of signs and symptoms of VL or, if symptomatic, negative parasitological investigations. Results: Among 243 patients assessed for eligibility, 150 were recruited between 2 January 2017 and 5 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; 90–100%) in the combination arm. Nineteen percent (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; 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. Conclusions: Combination therapy appears to be safe, well tolerated, and effective, and halves treatment duration of current recommendations. Clinical Trials Registration: Clinical Trial Registry India (CTRI/2015/05/005807; the protocol is available online at https://osf.io/avz7r ). Abstract : Evidence on treatments for visceral leishmaniasis infection in human immunodeficiency virus is sparse. This randomised trial showed that combination AmBisome and miltefosine resulted in 96% (72/75;95%CI 90–100) relapse free survival at day 210; whilst monotherapy with AmBisome resulted in 85% (64/75;95%CI 77–100).