The Project

Malaria infection during pregnancy is an important driver of maternal and neonatal health especially among HIV-infected women. In Africa, at least one million pregnancies are co-infected with malaria and HIV annually. The interaction between the two infections is particularly deleterious in pregnancy, leading to increased risk of malaria and HIV viral load, which may increase the frequency of mother to child transmission of HIV (MTCT-HIV). Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-uninfected women but it is contraindicated in those HIV-infected on cotrimoxazole prophylaxis (CTXp) due to potential adverse effects.

A recent trial showed that an effective antimalarial added to CTXp and long-lasting insecticide treated nets (LLITNs) in HIV-infected pregnant women improves malaria prevention and maternal health. However, the antimalarial used –mefloquine- was not well tolerated and it was associated with an increase in HIV viral load at delivery and a two-fold increased risk of MTCT-HIV. These findings highlight the need to find alternative drugs with better tolerability and safety profile to prevent malaria in this vulnerable group and to further study the pharmacological interactions between antimalarials and antiretrovirals (ARVs).

Work Packages

Overview of workplan

The project will include six work packages (WPs). Two of them (WP1 and WP6) relate to the Project Management and Communication, Advocacy and Exploitation activities, whereas WP2, and 3 comprise the main research tasks, and 4 and 5 will address Capacity Building and Networking actions. ISGlobal, as overall Project Coordinator leads the aforementioned WPs 1 and 6.

WP 1: Project Management

The Project Management WP is the essential “gluing” mechanism for the success of the project. WP1 will be coordinated by Dr Mireia Piqueras (ISGlobal, Spain) and deal with strategic direction, optimizing the use made of the project committees, and supervising WP leaders as they execute their role. It will entail overall steering of the project, thereby linking with all Executive Committee activities and receiving inputs and guidance from the external and independent Data Safety and Monitoring Board (DSMB). It will centralize all efforts addressed to maximize scientific quality of the project’s outputs, including quality assurance mechanisms, and guarantee continuous supervision of ethical issues on all the project’s fronts, including timely detection, analysis and documentation, therefore creating an ethical awareness layer that will impregnate all of the project activities.

The Scientific Coordination led by Prof. Clara Menéndez Santos, as overall project coordinator, will be fully aligned with all Project Management activities throughout the project, in order to ensure highly efficient and synergistic leadership efforts. All the African and European institutions involved in the project will be represented in the management of the consortium in order to ensure the coordination between partners and strengthen networking. The development of a management and coordination strategy is essential for efficient and effective implementation and monitoring of the project. In this sense, the tasks involved in this work package directly facilitate the accomplishment of the other work package objectives and the overall project goal, and include:

Establishment of the trial’s DSMB.
Development of a project management strategy to help ensure implementation and integration of work packages activities and minimize risks and conflicts that could arise during the project.
Developing and monitoring a project timeline to meet established milestones and objectives.
Developing a system for financial and contractual monitoring to ensure project funds are appropriate disbursed and used.

The MAMAH consortium will adopt the H2020 Governance structure for Large Projects, and so it is reflected in the Consortium Agreement.

WP2: Clinical Trial

The core of the Project activities is centred in the Clinical Trial under WP2, coordinated by Dr Francisco Saúte (Fundação Manhiça, Mozambique). The activities described in WP2 will be critical for the successful accomplishment of the project’s objectives by carrying out the proposed randomized placebo-controlled clinical trial in the two African institutions, in partnership with the three European institutions. Pregnant women enrolled in the clinical trial will be followed until the post-partum visit and their infants until one year of age.
Recruitment will start after ethical and regulatory clearances are obtained (expected during first semester of Project Year 2). Based on previous experience in the study countries, recruitment of 664 HIV-infected pregnant women is expected to last 20 months, the intervention will extend six additional months and the follow up is expected to be completed in the next 12 months (first semester of Project Year 5).
The WP2 leader will overview the entire development of the trial, in close collaboration to each site study’s coordinator. In addition, the trial will be externally supervised through the Data Safety Monitoring Board (DSMB), which will regularly meet (in person or “online”) to review the data generated.

WP3: Pharmacokinetics

The Pharmacokinetics (PK) sub-study activities will be coordinated by Prof. Michael Ramharter (Bernhard Nocht Institute for Tropical Medicine, Germany) and work in collaboration with Medicines for Malaria Venture (Geneva, Switzerland). PK activities will be linked to the Clinical Trial where a sub-sample of main trial participants will be invited to participate in the PK sub-study. Biological samples will be collected at pre-specified time points to determine the PK and pharmacodynamics features of study drugs (DHA-PPQ), as well as those of CTX and ARV drugs. Capillary blood samples will be collected onto filter paper from each participant. Filter papers will be dried and stored following manufacturer’s standard operating procedures prior to shipment for the PK analysis.
The results of the PK study are needed to fully characterize potential drug-drug interactions between DHA-PPQ and ARV drugs and CTX in African HIV-infected women.

WP4 : Capacity Building

WP4 will be coordinated by Dr Ghyslain Mombo-Ngoma (CERMEL, Gabon) and will have the support of Dr Heimo Lagler (Medical University of Vienna, Austria). The activities included in this work package will contribute to achieving the project objectives through collaboration between the European and African partners involved to develop the technical capacity and infrastructure required to carry out clinical trials for malaria control. Opportunities for capacity building will occur throughout the entire project in an integrated way. More specifically, this work package will:

Allow investigators and project teams in African sites to gain experience and expertise in new techniques and procedures through infrastructure and technology upgrades.
Provide training to trial’s staff at all levels in a range of relevant topics including: epidemiology, biostatistics, trial and data management, GCP, GCLP, etc.
Provide specific training opportunities at the postgraduate level to African research staff through on-site and academic training opportunities.
Strengthen existing collaboration between African and European institutions, as well as providing opportunities to develop new relationships and future capacity building activities.

WP5 Networking

The networking WP will be coordinated by Dr Meral Esen (University of Tübingen, Germany) and will contribute to the overall project objectives by facilitation of interaction between partners, as well as exchange of information with institutions involved in the broader maternal and child health community. Joint planning, problem solving, and sharing of knowledge will increase the strength and impact of the project. Since many issues faced at individual sites will be common among the partners, there will be opportunities for real-time learning and support. Other activities will include:

Facilitate frequent and meaningful contacts between partners through meetings, teleconferences, exchange visits, etc.
Provide formal and informal educational opportunities throughout the project.
Provide opportunities for participation in local, regional, and international meetings.
Increase attention to communication mechanisms with key stakeholders, communities, and the general public.

The team will explore possible synergies and concrete ways to coordinate and collaborate with any other EDCTP-funded proposals of the same or related topic.

WP6 Communication, advocacy and exploitation

WP6 will be coordinated by Dr Raquel González (ISGlobal, Spain). Especially important for the success of the project will be the establishment of a continuous communication flow. This will help to identify possible risks and implement appropriate contingency measures in the framework of the Executive Committee. A project Communication and Advocacy plan will be developed in order to ensure timely, accurate, and effective communication among partners, key stakeholders and the wider scientific community and public. Policies for external communication will be developed in order to ensure consistency across the Consortium in relation with the amount, form and content of any messages delivered to the target audiences. This activity will also comprise updates of the communication tools as required during the project lifetime. Finally, advocacy activities will be developed to raise awareness in order to increase access to antimalarials during pregnancy and quality ANC services for all but especially for HIV-infected pregnant women.