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Co-prevalent infections in adults with HIV-associated cryptococcal meningitis are associated with an increased risk of death: a nested analysis of the Advancing Cryptococcal meningitis Treatment for Africa (ACTA) cohort [version 1; peer review: awaiting peer review]

Ellis, J; Kalata, N; Dziwani, E; Matope, A; Wang, D; Molloy, SF; Harrison, TS; ... Heyderman, RS; + view all (2021) Co-prevalent infections in adults with HIV-associated cryptococcal meningitis are associated with an increased risk of death: a nested analysis of the Advancing Cryptococcal meningitis Treatment for Africa (ACTA) cohort [version 1; peer review: awaiting peer review]. Wellcome Open Research , 6 , Article 19. 10.12688/wellcomeopenres.16426.1. Green open access

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Abstract

Background: HIV-associated cryptococcal meningitis accounts for 15% of AIDS related deaths globally. In sub-Saharan Africa, acute mortality ranges from 24% to 100%. In addition to the mortality directly associated with cryptococcosis, patients with HIV-associated cryptococcal meningitis are at risk of a range of opportunistic infections (OIs) and hospital acquired nosocomial infections (HAIs). The attributable mortality associated with co-prevalent infections in cryptococcal meningitis has not been evaluated. Methods: As part of the Advancing Cryptococcal meningitis Treatment for Africa (ACTA) trial, consecutive HIV-positive adults with cryptococcal meningitis were randomised to one of five anti-fungal regimens and followed up until 10-weeks. We conducted a retrospective case note review of ACTA participants recruited from Queen Elizabeth Central Hospital in Blantyre, Malawi to describe the range and prevalence of OIs and HAIs diagnosed, and the attributable mortality associated with these infections. Results: We describe the prevalence of OIs and HAIs in 226 participants. Baseline median CD4 count was 29 cell/mm3, 57% (129/226) were on anti-retroviral therapy. 56% (127/226) had at least one co-prevalent infection during the 10-week study period. Data were collected for 187 co-prevalent infection episodes. Suspected blood stream infection was the commonest co-prevalent infection diagnosed (34/187, 18%), followed by community-acquired pneumonia (32/187, 17%), hospital-acquired pneumonia (13/187, 7%), pulmonary tuberculosis (12/187, 6%) and confirmed blood stream infections (10/187, 5%). All-cause mortality at 10-weeks was 35% (80/226), diagnosis of an OI or HAI increased the risk of death at 10 weeks by nearly 50% (HR 1.48, 95% CI 1.01-2.17, p=0.04). Conclusion: We demonstrate the high prevalence and broad range of OIs and HAIs occurring in patients with HIV-associated cryptococcal meningitis. These co-prevalent infections are associated with a significantly increased risk of death. Whether a protocolised approach to improve surveillance and proactive treatment of co-prevalent infections would improve cryptococcal meningitis outcomes warrants further investigation.

Type: Article
Title: Co-prevalent infections in adults with HIV-associated cryptococcal meningitis are associated with an increased risk of death: a nested analysis of the Advancing Cryptococcal meningitis Treatment for Africa (ACTA) cohort [version 1; peer review: awaiting peer review]
Open access status: An open access version is available from UCL Discovery
DOI: 10.12688/wellcomeopenres.16426.1
Publisher version: http://dx.doi.org/10.12688/wellcomeopenres.16426.1
Language: English
Additional information: © 2021 Ellis J et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: cryptococcal meningitis, opportunistic infections, hospital acquired infections, nosocomial infections, HIV/AIDS, Africa
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10121921
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