R&D MODEL & PORTFOLIO
New treatments for HIV/VL co-infection for Africa
PROJECT START: September 2011 OVERALL OBJECTIVE: Develop a new treatment regimen for
New treatments for PKDL for Asia/Africa
PROJECT START: March 2015 OVERALL OBJECTIVE: Evaluate the role of PKDL in transmission
patients co-infected with HIV/VL
2015 OBJECTIVE: Finalize recruitment into HIV/VL coinfection
and epidemiology of Leishmania parasites and to develop a new treatment
2015 OBJECTIVE: Carry out preparations for epidemiological,
study and conduct three interim analyses
infectivity, and PK and treatment studies
This study, initiated in 2014, aimed to evaluate the efficacy of a combination recruited at regimen of AmBisome® with miltefosine, 2 sites and of AmBisome® (at a higher dose) monotherapy in Ethiopian patients co-infected with VL and HIV. The AmBisome® monotherapy arm was dropped due to lower than expected efficacy at the time of the first interim analysis in April 2015, and recruitment into the remaining combination arm was also interrupted after the 2nd interim analysis in July for the same reason. Efficacy and safety data for the treatment period is currently under analysis. All 59 patients recruited continue the 12 months follow-up with pentamidine prophylaxis. The final clinical trial report is expected in 2016.
DNDi is prioritizing the management of PKDL patients who are believed to constitute a reservoir of infection for visceral leishmaniasis in the Indian Sub-continent and East Africa. A synopsis has been developed for a Phase II clinical trial of AmBisome® alone or in combination with miltefosine, to assess the safety and efficacy for the treatment of PKDL patients in India and Bangladesh, and AmBisome® or paromomycin in combination with miltefosine for the treatment of PKDL in Sudan. An infectivity study will also be conducted in both countries, to explore the role of PKDL as a potential reservoir of L. donovani parasites which can be spread by the sandfly. This is of particular concern in the period between epidemics, and the trial aims to ascertain if there is a need for chemotherapy for all PKDL patients to reduce transmission. It also aims to identify immunological biomarkers of infectivity in VL and PKDL cases. In preparation of the study, an insectarium was constructed at the SK hospital in Mymensingh, Bangladesh in 2015.
MAIN PARTNERS: International Centre for Diarrhoeal Disease Research (ICDDR,B), Bangladesh; Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), India; Kala Azar Medical Research Centre, India; Institute of Medical Sciences, Banaras Hindu University, Varanasi, India; Safdarjung Hospital, Delhi, India; Uppsala University, Sweden; Institute of Endemic Disease (IEND), Khartoum University, Sudan; Ministry of Health, Sudan; LEAP
In anthroponotic transmission areas (where disease is transmitted by the vector from human to animals), the WHO recommends secondary prophylaxis with drugs not given in treating primary VL cases to avoid resistance development. As part of the Africoleish consortium, the results from a separate study to assess pentamidine as prophylaxis to prevent VL relapses in HIV-VL population demonstrated monthly pentamidine infusions led to lower rates of VL relapses in HIV co-infected patients following one year of treatment.
MAIN PARTNERS: Gondar University Hospital, Ethiopia; Addis Ababa
University, Ethiopia; London School of Hygiene and Tropical Medicine (LSHTM), UK; Institute of Tropical Medicine (ITM) – Antwerp, Belgium; Médecins Sans Frontières (MSF), The Netherlands; Uppsala University, Sweden; Gilead Sciences, USA; LEAP; The Netherlands Cancer Institute, The Netherlands; Utrecht University, The Netherlands; BaseCon, Denmark; UBC, Switzerland
DNDi Annual Report 2015 › 33