ANRS DREAMM : Project to reduce the mortality rate of People Living with HIV and presenting with suspected central nervous system infection
In order to reduce the mortality of HIV-related infections of the central nervous system (CNS), ANRS | Emerging Infectious Diseases has sponsored – in conjunction with St George's University of London (SGUL) and the Pasteur Institute, and co-funded – in conjunction with the European and Developing Countries Clinical Trials Partnership (EDCTP), the ANRS DREAMM project: - Driving Reduced AIDS-associated Meningo-encephalitis Mortality. Its aim was to show that an appropriate and effective diagnostic and treatment model for people living with HIV (PLHIV) and presenting with suspected CNS infection can impact mortality in sub-Saharan Africa. It has also strengthened local health systems by mapping and optimizing clinical and laboratory pathways to reduce time to care. Conducted in three sub-Saharan African countries, Cameroon, Malawi, and Tanzania, the project was extended from 2016 to 2021.
One third of the advanced stages of HIV infection is caused by infections of the central nervous system (CNS). Cryptococcal meningitis is the leading cause of HIV-related meningo-encephalitis in some countries, responsible for around 15-20% of HIV-related deaths – with 135 900 annual deaths recorded in resource-limited countries. Studies show that 70% of the mortality rate is accounted for within 10 weeks of detection of the disease in under-resourced health establishments, because diagnoses confirming CNS infections are, among other things, rarely made in low-resource countries. Other reasons may also explain this high mortality rate: ineffective communication between the clinics receiving the patients and the diagnostic laboratories – with the latter often located far away from the former – delayed and/or ineffective treatment choices, lack of access to diagnostic tests and essential antifungal drugs, such as flucytosine and amphotericin B.
DREAMM was built on the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, sponsored and funded by the Medical Research Council (MRC) and ANRS, the results of which have enabled the World Health Organization (WHO) to adapt its cryptococcal meningitis treatment guidance by incorporating new regimens more appropriate for countries of the Global South compared with the hitherto standard treatment for HIV-infected patients presenting with cryptococcal meningitis.
According to the scientific teams, this was to their knowledge the first multi-center scientific implementation project on HIV-related CNS infection. The population studied included PLHIV of ≥18 years of age presenting with a first episode of suspected CNS infection.
The design (before/after) of DREAMM evaluated its impact on patient care and mortality rate in five public hospitals. The study consisted of three phases (observation, training, and implementation) :
- To begin with, an observation phase was set up to measure the mortality rate at two and ten weeks in 139 patients with suspected CNS infections. By describing the patients’ care based on their data, the team showed that in the observation phase there were 10% cases of CNS infection confirmed by microbiological testing, while in the implementation phase the rate was much higher, reaching 77% of people diagnosed using microbiological confirmation.
- During the training phase, the DREAMM project teams, in collaboration with local personnel, developed an open-access training guide to train all personnel involved in the study, so that patients arriving at the hospital could be integrated into the care system, screened, and put on treatment – in accordance with the latest local and WHO guidelines – within a very short time.
- 356 participants were then included in the implementation phase. The scientific teams implemented an algorithm for the management of HIV-related CNS infections by means of rapid diagnostic tests by the bedside as well as the treatment recommended by the WHO for cryptococcal meningitis* . They then evaluated the impact produced by the implementation of the new screening algorithm and the use of the treatment.
Importance of African hospital leadership in study implementation
The entire ANRS DREAMM project was led by local people in positions of responsibility (hospital director, research and implementation manager, health ministry, etc.). They developed a study design appropriate to each country so that the algorithm used corresponded to each site. This choice of implementation enabled the local players to best evaluate the preferred approach for the long-term implementation of the project as well as to design and adapt communication to their communities.
"The humanitarian approach is truly the essence of DREAMM. It is a fairness-based project that has put African players at the center of the decisions and has shown that when we give the right equipment (tests, drugs, etc.) to the hospital personnel and we offer them appropriate training while strengthening the hospital system, the same personnel are perfectly capable of reducing the HIV and meningitis mortality rate in a significant way."
Angela Loyse, coordinating investigator of the DREAMM project and Senior Lecturer in Infectious Diseases at St George’s, University of London
"This project has enabled us to return to good hospital practices, improving communication and the involvement of the various stakeholders in order to care for patients more effectively. DREAMM has also shown very good results, which is why we need these treatments and diagnostic capacities to be available because, by diagnosing early, we can treat early and therefore save lives. There is a real need to implement it on a broad scale."
Charles Kouanfack, principal investigator of the DREAMM project in Cameroon
The preliminary results of this study were presented at IAS 2021 and CROI 2022; the final results will also be published in an article very shortly.
* - Treatment used in Cameroon: two weeks of flucytosine combined with fluconazole (cf. 2nd line of the WHO 2018 guidelines, in accordance with the Ministry of Health guidelines
- Treatment used in Tanzania and Malawi: one week of amphotericin B combined with flucytosine (1st line of the WHO 2018 guidelines)
List of partner institutions :
• Amana Hospital (Dar es Salaam, Tanzania)
• Mwananyamala Hospital (Dar es Salaam, Tanzania)
• National Institute for Medical Research (NIMRI) (Tanzania)
• Kamuzu Central Hospital (Lilongwe, Malawi)
• Zomba Central Hospital (Zomba, Malawi)
• UNC Project Malawi (Lilongwe, Malawi)
• Lighthouse (Malawi)
• Hôpital Central de Yaoundé (Cameroon)
• Centre Pasteur du Cameroun (Yaoundé, Cameroon).
For more information :
ClinicalTrials.gov : https://clinicaltrials.gov/ct2/show/NCT03226379
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