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.

Treatment regimens

  • 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) 

Impact

  • 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.
  • 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

2022

WHO released new guidelines recommending the combination treatment of liposomal amphotericin B with miltefosine to treat people co-infected with HIV and visceral leishmaniasis. India, Ethiopia, and other countries where both diseases are endemic are expected to adapt their own treatment guidelines in the future to include the new treatment recommended by the WHO.

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.