Reduction in mortality from HIV-related CNS infections in routine care in Africa (DREAMM): a before-and-after, implementation study.

Autor:	Mfinanga S; National Institute for Medical Research, Muhimbili Medical Research Centre, Dar es Salaam, Tanzania; Department of International Public Health, Liverpool School of Tropical Medicine, Liverpool, UK., Kanyama C; University of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe, Malawi., Kouanfack C; University of Dschang, Dschang, Cameroon., Nyirenda S; Zomba Central Hospital, Zomba, Malawi., Kivuyo SL; National Institute for Medical Research, Muhimbili Medical Research Centre, Dar es Salaam, Tanzania., Boyer-Chammard T; Unité de Mycologie Moléculaire, Institut Pasteur, Université de Paris, Centre National de la Recherche Scientifique, Paris, France., Phiri S; Lighthouse Trust, Lilongwe, Malawi., Ngoma J; Kamuzu Central Hospital, Lilongwe, Malawi., Shimwela M; Amana Hospital, Dar es Salaam, Tanzania., Nkungu D; Mwananyamala Hospital, Dar es Salaam, Tanzania., Fomete LN; Yaoundé Central Hospital, Yaoundé, Cameroon., Simbauranga R; National Institute for Medical Research, Muhimbili Medical Research Centre, Dar es Salaam, Tanzania., Chawinga C; University of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe, Malawi., Ngakam N; Yaoundé Central Hospital, Yaoundé, Cameroon., Heller T; Lighthouse Trust, Lilongwe, Malawi., Lontsi SS; Yaoundé Central Hospital, Yaoundé, Cameroon., Aghakishiyeva E; Institute for Infection and Immunity, St George's University of London, London, UK., Jalava K; Wood Street Veterinary Hospital, Barnet, UK., Fuller S; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK., Reid AM; Leeds Institute of Medical Education, University of Leeds, Leeds, UK., Rajasingham R; University of Minnesota, Minneapolis, MN, USA., Lawrence DS; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana., Hosseinipour MC; University of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe, Malawi., Beaumont E; Department of Infectious Disease Epidemiology and International Health, London School of Hygiene and Tropical Medicine, London, UK., Bradley J; Department of Infectious Disease Epidemiology and International Health, London School of Hygiene and Tropical Medicine, London, UK., Jaffar S; UCL Institute for Global Health, University College London, London, UK., Lortholary O; Unité de Mycologie Moléculaire, Institut Pasteur, Université de Paris, Centre National de la Recherche Scientifique, Paris, France; Necker-Enfants Malades Hospital, Assistance Publique - Hôpitaux de Paris, Institut Hospitalier Universitaire Imagine, Paris, France., Harrison T; Institute for Infection and Immunity, St George's University of London, London, UK., Molloy SF; Institute for Infection and Immunity, St George's University of London, London, UK., Sturny-Leclère A; Institut Pasteur, Université Paris Cité, National Reference Center for Invasive Mycoses and Antifungals, Translational Mycology Research Group, Mycology Department, Paris, France., Loyse A; Unité de Mycologie Moléculaire, Institut Pasteur, Université de Paris, Centre National de la Recherche Scientifique, Paris, France; Institute for Infection and Immunity, St George's University of London, London, UK. Electronic address: aloyse@sgul.ac.uk.
Jazyk:	angličtina
Zdroj:	The lancet. HIV [Lancet HIV] 2023 Oct; Vol. 10 (10), pp. e663-e673.
DOI:	10.1016/S2352-3018(23)00182-0
Abstrakt:	Background: Four decades into the HIV epidemic, CNS infection remains a leading cause of preventable HIV-related deaths in routine care. The Driving Reduced AIDS-associated Meningo-encephalitis Mortality (DREAMM) project aimed to develop, implement, and evaluate pragmatic implementation interventions and strategies to reduce mortality from HIV-related CNS infection. Methods: DREAMM took place in five public hospitals in Cameroon, Malawi, and Tanzania. The main intervention was a stepwise algorithm for HIV-related CNS infections including bedside rapid diagnostic testing and implementation of WHO cryptococcal meningitis guidelines. A health system strengthening approach for hospitals was adopted to deliver quality care through a co-designed education programme, optimised clinical and laboratory pathways, and communities of practice. DREAMM was led and driven by local leadership and divided into three phases: observation (including situational analyses of routine care), training, and implementation. Consecutive adults (aged ≥18 years) living with HIV presenting with a first episode of suspected CNS infection were eligible for recruitment. The primary endpoint was the comparison of 2-week all-cause mortality between observation and implementation phases. This study completed follow-up in September, 2021. The project was registered on ClinicalTrials.gov, NCT03226379. Findings: From November, 2016 to April, 2019, 139 eligible participants were enrolled in the observation phase. From Jan 9, 2018, to March 25, 2021, 362 participants were enrolled into the implementation phase. 216 (76%) of 286 participants had advanced HIV disease (209 participants had missing CD4 cell count), and 340 (69%) of 494 participants had exposure to antiretroviral therapy (ART; one participant had missing ART data). In the implementation phase 269 (76%) of 356 participants had a probable CNS infection, 203 (76%) of whom received a confirmed microbiological or radiological diagnosis of CNS infection using existing diagnostic tests and medicines. 63 (49%) of 129 participants died at 2 weeks in the observation phase compared with 63 (24%) of 266 in the implementation phase; and all-cause mortality was lower in the implementation phase when adjusted for site, sex, age, ART exposure (adjusted risk difference -23%, 95% CI -33 to -13; p<0·001). At 10 weeks, 71 (55%) died in the observation phase compared with 103 (39%) in the implementation phase (-13%, -24 to -3; p=0·01). Interpretation: DREAMM substantially reduced mortality from HIV-associated CNS infection in resource-limited settings in Africa. DREAMM scale-up is urgently required to reduce deaths in public hospitals and help meet Sustainable Development Goals. Funding: European and Developing Countries Clinical Trials Partnership, French Agency for Research on AIDS and Viral Hepatitis. Translations: For the French and Portuguese translations of the abstract see Supplementary Materials section. Competing Interests: Declaration of interests AL, DSL, and JB all received support for this project from European and Developing Countries Clinical Trials Partnership (EDCTP), paid to their institutions. AL has received grants from EDCTP, the National Institute for Health and Care Research, and the National Institutes of Health, and consultancy fees from Unitaid to advise on the Unitaid-CHAI Advanced HIV Disease programme, all paid to St George's University of London; AL is also the Chair and Lead of the End AIDS Action Group, which encompasses the work of the Cryptococcal Meningitis Action gorup, an unfunded role. RR received a grant from The National Institute of Allergy and Infectious Diseases, paid to their institution. OL receives consulting fees and payments or honoraria of less than US$1000 per year from Gilead Sciences; and is part of the advisory board for Mundipharma. THa received an investigator award from Gilead Sciences and has received payments or honoraria from Gilead Sciences and Pfizer for speaking fees. All other authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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