CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

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Clinical Outcomes of People With HIV-Cryptococcal Meningitis on the New Treatment Regimen in Uganda Olivie C. Namuju 1 , Richard Kwizera 2 , Lillian Tugume 1 , David R. Boulware 3 , David B. Meya 1 1 Infectious Disease Institute, Kampala, Uganda, 2 Makerere University College of Health Sciences, Kampala, Uganda, 3 University of Minnesota, Minneapolis, MN, USA Background: Cryptococcal meningitis (CM) remains the second most lethal opportunistic infection among People Living with HIV in sub-Saharan Africa. CM is managed on single high-dose liposomal amphotericin B and flucytosine. However, there is no sufficient data on whether the new treatment regimen has an effect on reducing inpatient mortality and length of hospital stay in the real-world setting. We aimed to investigate the proportion of inpatient mortality, length of hospital stay (LOS), and factors associated with mortality among patients with HIV-associated CM receiving liposomal amphotericin B-flucytosine regimen. Methods: This was a cross-sectional study conducted to review medical records of patients admitted between December 2022 and May 2023 at 11 tertiary hospitals in Uganda. Medical records of 173 HIV-CM patients were reviewed. Univariate descriptive statistics were used to summarize the background characteristics. Modified Poisson regression was used to ascertain factors associated with mortality at bivariable and multivariable levels. Associations were presented through adjusted prevalence ratios with their 95% confidence intervals. Data were analyzed using STATA v15. Results: Of the 173 patients’ medical records reviewed, the majority (58.4%), were males with a median age of 38 years (IQR= 30, 48) and over half (55.5%) were married. Forty percent of the patients had altered mental status (GCS<15) on admission. Overall, inpatient mortality for liposomal amphotericin B was 35.8% (compared to 42% of amphotericin B deoxycholate) and this significantly varied by health facility (range 7.1-100%). The median LOS was 7 days (IQR = 3, 12). Factors associated with mortality were male sex [adjusted prevalence ratio (APR); 1.87, 95%CI (1.21-2.87)], p-value=0.005), admission with a convulsion [APR, 1.86, 95%CI (1.21-2.86), p-value=0.005)], altered mental status [APR; 1.66, 95%CI (1.07-2.57), p-value=0.023], and presence of a comorbid condition [APR, 2.26 95%CI (1.44-3.53), p-value=0.006]. Therapeutic lumbar punctures were significantly associated with reduced mortality [APR; 0.47, 95%CI (0.29 0.73), p-value=0.001]. Conclusions: Liposomal amphotericin B regimen has lower mortality in the real-world setting. Patients on average spend more than a week in hospital. Male sex, admission with a convulsion, altered mental status, and comorbid conditions were independently associated with mortality. Therapeutic LPs significantly reduced inpatient mortality. Trends in Cryptococcal Meningitis Mortality Using Routine Longitudinal National Data From Botswana James Milburn 1 , Ookeditse Ntwayagae 2 , Jodie Russell 1 , Tony Chebani 3 , Tshepo Leeme 4 , David S. Lawrence 5 , Daniel Grint 5 , Mark Tenforde 6 , Ava Avalos 7 , Dinah Ramaabya 3 , Justus Ogando 8 , Margaret Mokomane 9 , Madisa Mine 10 , Joseph N. Jarvis 5 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 Botswana University of Maryland School of Medicine Health Initiative (Bummhi), Gaborone, Botswana, 3 Botswana Ministry of Health, Gaborone, Botswana, 4 University of Botswana, 5 London School of Hygiene & Tropical Medicine, London, UK, 6 Botswana–UPenn Partnership, Gaborone, Botswana, 7 Botswana–Harvard AIDS Institute Partnership, Gaborone, Botswana, 8 Clinton Health Access Initiative, Boston, MA, USA, 9 University of Botswana, Gaborone, Botswana, 10 National Health Laboratory, Gaborone, Botswana Background: Cryptococcal meningitis (CM) remains a frequent opportunistic infection among individuals with advanced HIV disease, causing significant morbidity and mortality. CM incidence has fallen in high HIV-prevalence settings with expansion of ART. Few countries other than South Africa collect reliable data on CM; robust longitudinal data describing the impact of HIV programme interventions and changes in management of CM on mortality in the rest of Africa are lacking. Methods: National mortality estimates from CM in Botswana were described using 8 years of national meningitis surveillance data (2015-2022) from electronic health records. All laboratory records from CSF samples analysed in government healthcare facilities in Botswana were extracted from a central online repository. CM case frequency was enumerated using a case definition. Mortality data were manually extracted from the national registry in duplicate using national identification numbers with arbitration by a third reviewer in discrepant cases. Outcomes were stratified as short-term (2 weeks), medium term (10 weeks), long-term (1 year) from lumbar puncture date, and analysed by

calendar year. Repeat presentation and cases without a national identification number were excluded. Results: Outcome data from 1259 first presentations of CM between 2015-2022 were analysed. Mortality at 2 weeks was 19% (95% CI 0.14-0.25, 37/193) in 2015 and 23% (95% CI 0.16-0.33, 24/103) in 2022, at 10 weeks 27% (95% CI 0.21-0.34, 52/193) and 32% (95% CI 0.23-0.42, 33/103) and at 1 year 32% (95% CI 0.25-0.38, 60/193) and 38% (95% CI 0.28-0.48, 39/103), respectively, with no clear temporal trend (fig 1). Early mortality was significantly higher in older patients and those with positive CSF India ink, or lower CSF protein, glucose, or white cell count. Early mortality was higher in district or primary hospitals (21.5%, 165/767) compared to referral hospitals (19.8%, 111/561), OR 1.6 (CI 1.3-1.9, p<0.01). Conclusions: Mortality from CM in Botswana remains high with no evidence of decline in 8 years of observation despite excellent ART coverage and improved diagnosis and management strategies. Increased mortality was observed in 2020, likely either directly attributable to COVID-19 or indirectly from disruptions to healthcare services. Treatment for CM has been simplified in updated WHO guidelines but access to effective antifungals including flucytosine in resource-limited settings remains restricted and must be addressed to reduce mortality.

Poster Abstracts

976

Pathway to Care Among Inpatients With Symptomatic Cryptococcal Meningitis in Johannesburg, SA Lia F. Edkins 1 , Raphaela Berghammer-Bohmer 2 , Asha MK Thombrayil MBChB 2 , Jeremy Nel 2 , Merika Tsitsi 2 , Susan T. Meiring 3 , Rudzani C. Mashau 3 , David S. Lawrence 4 , Kennedy Mupeli 5 , Joseph N. Jarvis 4 , Thomas S. Harrison 6 , Tom Boyles 7 , Nelesh P. Govender 2 , Rachel Wake 8 , Síle Molloy 6 , for the IMPRINT Research Group 1 WITS Health Consortium, Johannesburg, South Africa, 2 University of Witwatersrand, Johannesburg, South Africa, 3 National Institute for Communicable Diseases, Johannesburg, South Africa, 4 London School of Hygiene & Tropical Medicine, London, UK, 5 Centre for Youth of Hope (CEYOHO), Gaborone, Botswana, 6 St George's University of London, London, UK, 7 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 8 St George's University Hospitals NHS Foundation Trust, London, UK Background: Cryptococcal antigen (CrAg) screening and pre-emptive treatment reduces risk of HIV-associated cryptococcal meningitis (CM) and death. Understanding the pathway to care following serum CrAg (sCrAg) screening is crucial for improving screening practices for people with advanced HIV disease. Methods: We conducted structured interviews and collated hospital and laboratory data about patients with HIV-associated symptomatic CM at two tertiary-level hospitals in Johannesburg in South Africa, following informed consent. If done, prior sCrAg results were obtained from the Laboratory Information Management System. Participants were asked about their pathway to care prior to presentation. Results: Among 126 participants with symptomatic CM (median CD4 count 24 cells/uL, IQR 9 – 52), 33% (41/126) of participants had ever undergone sCrAg screening prior to hospital admission, of whom 59% (24/41) had a positive result. Of those with available data, 74% (17/23) had no CM symptoms at the time of sCrAg testing and the average delay until symptom onset was 22 days (range 1 – 509). Of those without symptoms, 93% (13/14) visited a healthcare provider following testing, however only 22% (2/9) were known to receive any fluconazole prior to hospitalisation. Of those who did not take fluconazole, 17% (1/6) declined fluconazole, 17% (1/6) were referred for LP without fluconazole,

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CROI 2025 308