This project intends to carry out studies by 2016 that are essential for future evaluation of a potential oral combination for VL infections. It also aims to bring to patients affected by VL-HIV in East Africa a package of care composed of new treatment options for VL and a preventive intervention option to avoid relapses. These studies will ultimately allow to bring cost-effective and suitable therapeutic interventions to both primary VL and VL-HIV co-infected patients.

Identification of a new oral combination therapy
The studies in the AfriCoLeish project are a Phase II Proof-of-Concept trial to assess the safety and efficacy of a new oral treatment for VL (fexinidazole) and a miltefosine allometric dose pharmacokinetics and safety study in paediatric VL patients (Work Package 1).

  • The Phase II Proof-of-Concept (PoC) clinical trial is the first study to assess efficacy and safety of fexinidazole as a new oral treatment for primary VL patients. Adults aged 15- 60years will be treated with the 10 day course treatment, which is the same regimen used for HAT patients, and very well tolerated. Patients will be continuously monitored for safety, and efficacy evaluations will be done at the end of treatment and after 6 months post treatment.
  • Results from the LEAP 0208 study indicated that children treated with miltefosine were underexposed as compared to adults and this was reflected in a poorer clinical outcome over the 6 months after treatment. Therefore, a further study will assess PK and safety of miltefosine allometric dose given twice a day (BID) for 28 days in paediatric VL patients aged 4-12y. Efficacy assessment at end of treatment and 6 months follow-up will be a secondary endpoint for this study. Results from this study will guide how to best adjust miltefosine dose in VL patients (especially children), as well as duration of treatment when used in combination.

Promising results of these two studies would allow moving forward with the development of new treatments, including the assessment of the efficacy and safety of a potential oral combination.

New treatment options for patitents with HIV and VL
Monthly pentamidine secondary prophylaxis (4 mg/kg IV, every 3-4 weeks) may reduce the risk of relapse and improve long-term survival of co-infected patients (Work Package 2). In addition, new regimens tested for HIV-VL co-infected patients (high dose AmBisome 40 mg/kg, high dose combination of AmBisome (30mg/kg) and miltefosine for 28 days) will offer the possibility of achieving high initial cure rates of VL, contributing to reduced disease burden on patients and health systems (Work Package 3). Through this randomized clinical trial in Eastern Africa, the project will, for the first time, provide conclusive evidence-based data on the WHO recommendation to treat kala-azar/HIV co-infected patients using AmBisome 40 mg/kg total dose, and on the locally used regimen of AmBisome 30mg/kg in combination with Miltefosine that is used by MSF in Ethiopia. The additional key innovation will be to combine these two elements with early commencement of anti-retroviral therapy (ART) as a standard package of care for VL-HIV co-infected individuals. As data will be collected in prospective studies, the outcomes obtained will not only be important for the region but also other areas where VL-HIV co-infection exists, including Europe, Asia and Latin America.

Translation into policy and implementation of treatments
A critical element will be the ongoing close collaboration with stakeholders such as National Control Programmes, State health providers and key NGOs to secure commitment and to bridge the gap between clinical trials / registration, policy recommendation and implementation in the field; these activities, as well as wider advocacy and awareness-raising activities, are integrated in a Dissemination of results to support translation into policy and implementation of treatments work package.

All the Consortium partners are part of the Leishmaniasis East Africa Platform (LEAP Platform). In addition to its capacity building role for the implementation of clinical studies in the region, LEAP plays an important support role in the AfriCoLeish project as it effectively provides a platform to disseminate and validate the results of the clinical trials, and in turn provides a forum for the exchange of information, allowing for the efficient translation of research results into policy. Thus, LEAP will play a key role in driving the amendment of national treatment guidelines, and ultimately in ensuring patients´ access to the new treatments.