Identify and deliver a safe and highly effective treatment that will improve long-term survival for people living with both visceral leishmaniasis and HIV
current phase of drug development
updated 18 Mar 2024
Safe and effective treatment for people living with both HIV and visceral leishmaniasis
First evidence-based treatment for a highly vulnerable population
People living 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 patients living with both HIV and visceral leishmaniasis 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 World Health Organization (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 living with both visceral leishmaniasis and HIV, recommending a combination of liposomal amphotericin B with miltefosine.
Treatment regimens
- Indication: visceral leishmaniasis in people living with HIV
- Dosage in East Africa: liposomal amphotericin B (up to a total dose of 30 mg/kg, at 5 mg/kg on days 1, 3, 5, 7, 9, 11) + miltefosine (100 mg/day for 28 days)
- Dosage in South-East Asia: liposomal amphotericin B (up to a total dose of 30 mg/kg, at 5 mg/kg on days 1, 3, 5, 7, 9, 11) + miltefosine (100 mg/day for 14 days)
Impact
- WHO 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.
- In November 2022, the Ethiopian Ministry of Health adopted the combination treatment liposomal amphotericin B and miltefosine as the country’s first-line treatment regimen for visceral leishmaniasis in people living with HIV.
- 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
Project updates
2023
Following the adoption of the new recommendations for the treatment of visceral leishmaniasis in people living with HIV in Ethiopia, training was provided to 27 health workers caring for this patient population across eight health facilities in the Amhara Region, Oromia Region, and Southern Nations, Nationalities, and Peoples’ Region of Ethiopia. Forty-nine people living with HIV and visceral leishmaniasis were treated with the newly recommended liposomal amphotericin B and miltefosine combination therapy in the DNDi-supported Leishmaniasis Research and Treatment Center in Gondar, Ethiopia.
2022
The World Health Organization (WHO) issued new guidelines recommending the use of a combination treatment of liposomal amphotericin B and miltefosine for the treatment of visceral leishmaniasis in people living with HIV. Countries such as India and Ethiopia where both diseases are prevalent are expected to adopt these guidelines and incorporate the recommended treatment into their national treatment protocols.
2021
The WHO Guideline Development Group evaluated the treatment recommendations for HIV and visceral leishmaniasis co-infection in South Asia and Eastern Africa. Updated recommendations are expected in the first quarter of 2022.
2020
The WHO Guideline Development Group began evaluating HIV and visceral leishmaniasis co-infection treatment recommendations for South Asia and Eastern Africa; updated recommendations are expected in 2021.
2019
DNDi and the Rajendra Memorial Research Institute acted as technical partners in a Phase III study sponsored by MSF in India to evaluate currently recommended liposomal amphotericin B (LAmB) therapy and a combination of LAmB and miltefosine for the treatment of VL in patients co-infected with HIV. The last patient follow-up visit for the study was completed in May 2019 and the publication of study results is expected in 2020. Results of this study and the Phase III study on HIV/VL co-infected patients in Ethiopia will be reviewed in early 2020 by a World Health Organization Guideline Development Group evaluating treatment recommendations for people co-infected with visceral leishmaniasis and HIV.
2018
Results demonstrated the high efficacy of the combination therapy with a 67% cure rate when treatment lasted 28 days, increasing to an 88% cure rate when patients who were not cured received a second round of treatment to clear the parasite, with a full treatment lasting 58 days. Results were presented to the authorities in Ethiopia, and guidelines are under review to consider adopting the new combination treatment.
In addition, top-line results of a Phase III study sponsored by MSF in India, in which DNDi and the Rajendra Memorial Research Institute acted as technical partners, are expected in 2019. These complementary results should support discussions with national and international stakeholders for a new treatment recommendation for visceral leishmaniasis in people co-infected with HIV.
2017
Main efficacy results were presented to the Ethiopian authorities and WHO in Addis Ababa, Ethiopia, in June and December 2017, to promote the implementation of the combination of AmBisome® and miltefosine as first line treatment for HIV/VL co-infected patients, using the strategy of one or two treatment cycles. A scientific paper should be published in 2018 and open the discussions with other stakeholders to support new recommendation for HIV/VL co-infection.
In India, DNDi is technical partner with the Rajendra Memorial Research Institute (RMRI) in a study sponsored by MSF and launched in Bihar in 2017. This Phase III study will test Ambisome monotherapy and Ambisome in combination with miltefosine in 150 patients. 113 patients have been included so far. Recruitment is expected to be completed by early 2018. Results will inform the national road map of kala-azar elimination in India.
2016
With the extended treatment duration, results achieved with the combination treatment were found to be very promising, with the majority of patients achieving visceral leishmaniasis cure. These results were based on a limited number of patients; a new HIV/VL study is therefore under consideration to confirm the results.
News & resources
- 28 March 2024 - 2023 R&D portfolio in review: Leishmaniasis
- 27 January 2023 - Eliminating neglected diseases in Africa: there are good reasons for hope, The Conversation Africa
- 15 December 2022 - Leishmaniasis breakthrough year: new treatments, research, and partnerships
- 27 August 2022 - Una nueva esperanza para los ‘sentenciados a muerte’ de la leishmaniasis visceral y el VIH, El País
- 1 August 2022 - Guidelines for visceral leishmaniasis and HIV co-infection, The Lancet Infectious Diseases
- 7 July 2022 - A nasty disease is even nastier for patients with HIV. Now there’s encouraging news, NPR
- 14 June 2022 - A new hope for people with visceral leishmaniasis and HIV co-infection
- 8 June 2022 - The Science Explained: Evaluating new treatment regimens for visceral leishmaniasis in people living with HIV in India and Ethiopia
- 8 June 2022 - New WHO treatment guidelines offer hope for people co-infected with visceral leishmaniasis and HIV
- 11 February 2022 - 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 III trial, Clinical Infectious Diseases
- 2 March 2021 - Low antileishmanial drug exposure in HIV-positive visceral leishmaniasis patients on antiretrovirals: An Ethiopian cohort study, Journal of Antimicrobial Chemotherapy
- 21 February 2019 - 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
- 18 January 2019 - An HIV/VL patient’s long road to better treatment
- 17 January 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
- 17 January 2019 - Combination therapy found to be more effective in treating patients with leishmaniasis and HIV
- 24 May 2017 - The search for treatments for HIV/VL co-infected patients continues
- 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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