Identify and deliver a safe and highly effective treatment that will improve long-term survival for people with visceral leishmaniasis and HIV co-infection
current phase of drug development
updated 8 Jun 2022
Safe and effective treatment for people co-infected with HIV and visceral leishmaniasis
First evidence-based treatment for this highly vulnerable population
People co-infected with HIV and visceral leishmaniasis rarely achieve sustainable control of the visceral parasite – they have poor response to treatment, higher risk of death, and often experience multiple relapse episodes. In 2011, in an effort to improve treatment options, Médecins Sans Frontières (MSF) began administering a new regimen under compassionate use to co-infected patients in Abdurafi Health Centre in North-West Ethiopia; the treatment combines liposomal amphotericin B with the oral drug miltefosine.
Following promising results, DNDi and partners conducted a Phase III study, starting in 2014, to compare liposomal amphotericin B monotherapy – the WHO and international recommendations at the time – with a combination of liposomal amphotericin B infusions and oral miltefosine. In this study in Ethiopia, the new treatment strategy was shown to have an 88% efficacy rate at the end of therapy (after 58 days), whereas the efficacy of the current standard treatment was 55% in the trial.
Meanwhile in India, a similar MSF-led study showed the new treatment regimen was efficacious for 96% of cases after 210 days, while a lower rate of 88% was observed for cases receiving the standard treatment.
Based on the results of these two studies, in June 2022 WHO released new treatment guidelines for the treatment of people co-infected with visceral leishmaniasis and HIV, recommending a combination of liposomal amphotericin B with miltefosine.
- Indication: visceral leishmaniasis in people living with HIV
- Dosage in East Africa: liposomal amphotericin B (up to a cumulative treatment dose of 30 mg/kg body weight, given as 5 mg/kg on each treatment day 1, 3, 5, 7, 9, 11) + miltefosine (100 mg/day for 28 days)
- Dosage in South-East Asia: liposomal amphotericin B (≤ 30 mg/kg, at 5 mg/kg on days 1, 3, 5, 7, 9, 11) + miltefosine (100 mg/day for 14 days)
- The World Health Organization has reviewed all available evidence, including the results of these two trials, and has issued new treatment guidance for visceral leishmaniasis and HIV co-infection as of June 2022, with the liposomal amphotericin B and miltefosine combination as the recommended treatment for visceral leishmaniasis in people living with HIV.
- The Ethiopian government is changing their national treatment guidelines for visceral leishmaniasis and HIV co-infection to make the liposomal amphotericin B and miltefosine combination the country’s new first-line treatment regimen.
- The Indian government is also planning to update their treatment guidelines.
‘It is often hard to treat people living with these two diseases, because their weakened immune systems do not respond well to standard treatments. The new treatment greatly increases their chance of being cured during a visceral leishmaniasis occurrence.’
Dr Rezika Mohammed, Assistant Professor of Internal Medicine, University of Gondar, and Principal Investigator of the study in Ethiopia
Key scientific articles
- AmBisome monotherapy and combination AmBisome – miltefosine therapy for the treatment of visceral leishmaniasis in patients co-infected with HIV in India: a randomised open label, parallel arm, phase 3 trial. Clinical Infectious Diseases, February 2022.
- Low antileishmanial drug exposure in HIV-positive visceral leishmaniasis patients on antiretrovirals: an Ethiopian cohort study. Journal of Antimicrobial Chemotherapy, May 2021
- Long term outcomes and prognostics of visceral leishmaniasis in HIV infected patients with use of pentamidine as secondary prophylaxis based on CD4 level: a prospective cohort study in Ethiopia. PLOS Neglected Tropical Diseases, February 2019.
- A randomized trial of AmBisome® monotherapy and AmBisome® and miltefosine combination to treat visceral leishmaniasis in HIV co-infected patients in Ethiopia. PLOS Neglected Tropical Diseases, January 2019.
News and press releases
- 8 June 2022 – New WHO treatment guidelines offer hope for people co-infected with visceral leishmaniasis and HIV
- The Science Explained: Evaluating new treatment regimens for visceral leishmaniasis in people living with HIV in India and Ethiopia
- 17 January 2019 – Combination therapy found to be more effective in treating patients with leishmaniasis and HIV
- 6 October 2014 – Phase III clinical study in Ethiopia launched to test two treatments for HIV-visceral leishmaniasis co-infected patients
- 23 April 2013 – International consortium, to bring new treatments for kala-azar patients in East Africa, receives funding boost from European Union
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