- Target disease: HIV/VL co-infection
- Main partners (AfriCoLeish): Addis Ababa University, Ethiopia; BaseCon, Denmark; Gilead Sciences, USA; Gondar University Hospital, Ethiopia; Institute of Tropical Medicine Antwerp, Belgium; LEAP; London School of Hygiene & Tropical Medicine, UK; Médecins Sans Frontières, Spain; Médecins Sans Frontières, The Netherlands; Netherlands Cancer Institute, The Netherlands; Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), India; Sanofi, France; UBC, Switzerland; Uppsala University, Sweden; Utrecht University, The Netherlands.
- Project start: September 2011
- Funding (since project start): Department for International Development (DFID), UK; Dutch Ministry of Foreign Affairs (DGIS), The Netherlands; European Union – Specific International Scientific Cooperation Activities (FP7); Federal Ministry of Education and Research (BMBF through KfW), Germany; Médecins Sans Frontières/Doctors without Borders, International; Medicor Foundation, Liechtenstein; Spanish Agency for International Development Cooperation (AECID), Spain; Swiss Agency for Development and Cooperation (SDC), Switzerland; Other private foundations and individuals.
People co-infected with HIV and VL rarely achieve sustainable control of the parasite and present multiple episodes of relapse. In 2011, MSF began using a compassionate regimen, combining liposomal amphotericin B (often better known as AmBisome, the brand name of the drug produced by Gilead) with the oral drug miltefosine in Abdurafi Health Centre in North-West Ethiopia. To provide the necessary scientific evidence, DNDi ran a Phase
III study, starting in 2014, testing both AmBisome monotherapy as per current WHO and international recommendations, and a combination of AmBisome infusion and miltefosine orally for 28 days in 58 HIV/VL patients in two sites in Ethiopia. After 132 patients had been enrolled, recruitment was interrupted at the time of the second interim analysis, as efficacy at the end of treatment was lower than expected. Patients who had not achieved cure at the end of treatment were given a second cycle of the same treatment.
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 VL in people co-infected with HIV.
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.
With the extended treatment duration, results achieved with the combination treatment were found to be very promising, with the majority of patients achieving VL cure. These results were based on a limited number of patients; a new HIV/VL study is therefore under consideration to confirm the results.
Last update: August 2019