CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

and 67% (4) were seen by a healthcare provider but neither fluconazole nor LP were offered. Conclusions: Around a third of participants had sCrAg screening prior to presentation with symptomatic CM and almost two thirds of these results were positive. The majority of participants who were sCrAg positive did not have any symptoms of meningitis at the time of sCrAg testing. Overall, 14% of all patients presenting with symptomatic crypotococcal meningitis had previously had asymptomatic cryptococcal antigenaemia. Most asymptomatic sCrAg-positive patients did not receive fluconazole or have a LP, despite accessing healthcare services. This study highlights missed opportunities for reducing the incidence of CM and death in patients with advanced HIV disease, despite the reflexive CrAg screening programme in South Africa. Efforts to improve health worker and patient understanding around CrAg screening and recommended management are essential.

associated with double the odds of both 2-week (aOR 1.98 95%CI 1.01-3.88) and 10-week mortality (aOR 2.15, 95%CI 1.22-3.78) after adjustment for age, sex, CD4 count and study site. CMV CNS co-infection was associated with a non significant increase in mortality. EBV viraemia, and EBV CNS co-infection, were weakly associated with improved survival ( Table 1 ). Conclusions: EBV co-infections were associated with a pro-inflammatory cryptococcal phenotype known to be associated with improved survival (suggesting that EBV is a probable by-stander infection), whilst CMV viraemia was associated with a pauci-inflammatory response, higher fungal burdens and increased mortality. CMV viremia >1000IU/ml represents a potentially modifiable risk factor to improve survival amongst adults with cryptococcal meningitis. Interventional trials are required to understand how treatment of CMV impacts immune-modulation in advanced HIV disease.

Poster Abstracts

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Catastrophic Healthcare Expenditure From Cryptococcal Meningitis in Eastern and Southern Africa David S. Lawrence 1 , Charles Muthoga 2 , Jack Adams 3 , Buhle Ndweni 4 , Cecilia Kanyama 5 , Graeme Meintjes 4 , David B. Meya 6 , Mosepele Mosepele 2 , Henry Mwandumba 7 , Conrad Muzoora 8 , Chiratidzo Ndhlovu 9 , Síle Molloy 3 , Thomas S. Harrison 3 , Lucy Cunnama 4 , Joseph N. Jarvis 1 , for the AMBITION Study Group 1 London School of Hygiene & Tropical Medicine, London, UK, 2 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 3 St George's University of London, London, UK, 4 University of Cape Town, Cape Town, South Africa, 5 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 6 Infectious Diseases Institute, Kampala, Uganda, 7 Malawi Liverpool Wellcome Trust, Blantyre, Malawi, 8 Mbarara University of Science and Technology, Mbarara, Uganda, 9 University of Zimbabwe, Harare, Zimbabwe Background: HIV-associated cryptococcal meningitis is the second leading cause of AIDS-related mortality. Cryptococcal meningitis is a poverty-related disease and the majority of cases occur in settings where resources are limited and access to quality care is often linked to an individual’s ability to pay for services. We have previously demonstrated the efficacy, safety, and cost effectiveness of a single, high-dose liposomal amphotericin-based treatment regimen within the AMBITION-cm trial. Here we present a five-country, within-trial analysis exploring the individual economic impact of cryptococcal meningitis. Methods: 810 participants were recruited into this sub-study in Botswana, Malawi, South Africa, Uganda and Zimbabwe. We collected data on annual household expenditure, direct costs and indirect costs incurred prior to enrolment and during the ten-week trial period. Costs were inflated and converted to 2022 USD. We calculated out-of-pocket expenditure, lost income, and catastrophic healthcare expenditure. We defined catastrophic healthcare expenditure as costs exceeding 20% of annual household expenditure. Results: The average total out-of-pocket expenditure plus lost income prior to enrolment was $132. By the point of enrolment 18% (145/810) of participants had already experienced catastrophic healthcare expenditure. Among the 592 participants who survived to ten-weeks, combining out-of-pocket expenditure and lost income, the average individual cost was $516, ranging from $230 in South Africa to $592 in Zimbabwe. More than half (51%, 296/581) experienced catastrophic healthcare expenditure by the end of the trial, ranging from 16% (13/81) in South Africa to 68% (156/229) in Uganda. Conclusions: This is the first study exploring the individual economic impact experienced by individuals diagnosed with cryptococcal meningitis. The personal economic impact of cryptococcal meningitis is high and more than half of individuals who survive experience catastrophic healthcare expenditure. It is likely these figures are higher outside of the research setting. This highlights the profound financial impact of this devastating infection and provides a rationale to offer financial and social protection to those affected.

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CMV and EBV Coinfections and Mortality Risk in Patients With HIV-Associated Cryptococcal Meningitis Jayne P. Ellis 1 , Elisabetta Groppelli 2 , Ronan Doyle 1 , David S. Lawrence 1 , David B. Meya 3 , David R. Boulware 4 , Henry Mwandumba 5 , Cecilia Kanyama 6 , Mina Hosseinipour 7 , Graeme Meintjes 8 , Conrad Muzoora 9 , Mosepele Mosepele 10 , Chiratidzo Ndhlovu 11 , Thomas S. Harrison 2 , Joseph N. Jarvis 1 , for the AMBITION Study Group 1 London School of Hygiene & Tropical Medicine, London, UK, 2 St George's University of London, London, UK, 3 Infectious Diseases Institute, Kampala, Uganda, 4 University of Minnesota, Minneapolis, MN, USA, 5 Malawi Liverpool Wellcome Trust, Blantyre, Malawi, 6 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 7 University of North Carolina Project–Malawi, Lilongwe, Malawi, 8 University of Cape Town, Cape Town, South Africa, 9 Mbarara University of Science and Technology, Mbarara, Uganda, 10 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 11 University of Zimbabwe, Harare, Zimbabwe Background: Cryptococcus is the most common cause of HIV-associated meningitis globally, accounting for 19% of all AIDS-related deaths. Case fatality is 24-45%, even in the context of clinical trials. Co-prevalent infections – including Cytomegalovirus (CMV) and Epstein–Barr virus (EBV) - may contribute to poor outcomes. Methods: We measured CMV and EBV viral load by qPCR in baseline plasma and CSF samples collected prospectively as part of AMBITION-CM, a multi-site, randomized trial which investigated the use of single high dose liposomal amphotericin B for the treatment of HIV-associated cryptococcal meningitis. The AMBITION-CM trial was conducted in Uganda, Botswana, South Africa, Malawi and Zimbabwe. We described the prevalence of CMV- and EBV-viraemia (in plasma), and CNS co-infections (CSF qPCR positivity), and associations of any detectable CMV- or EBV-viremia or viremia >1000 IU/ml with 2- and 10-week mortality using logistic regression modelling. Results: 825 AMBITION-CM participants were included: 61% male, median age 37 years (IQR 32-43), median baseline CD4 count 33 cells/μL (IQR 12-67). EBV plasma viraemia was present in 73% (600/825), and CMV viraemia in 49% (418/825). CNS co-infections were less common; 27% had detectable EBV in CSF, and 5% had detectable CMV. CMV plasma viraemia was significantly associated with lower CD4 counts, less CSF inflammation, and higher CSF fungal burdens. Conversely, EBV plasma viraemia was positively associated with higher CD4 counts and more CSF inflammation. CMV plasma viraemia (>1000IU/ml) was

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CROI 2025 309