CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

at 10 weeks. There was a significant interaction between the clinical decision to interrupt ART at enrolment and ART timing on mortality risk (p= 0.01); Among individuals on ART for less than 14 days in the AMBITION trial, 2-week mortality was 35% (8/23) with continued ART versus 14% (7/42) in those who discontinued ART (p=0.05). Conclusion: Our findings show an increased risk of early mortality in cryptococcal meningitis patients who started ART in the past 2 weeks in keeping with prior preliminary data. ART interruption at CM diagnosis in recent ART initiators does not lead to increased mortality and may be associated with improved outcomes. Intervention studies are needed to definitively determine whether ART interruption in patients presenting with cryptococcal meningitis having recently started ART is beneficial. CSF HIV Viral Escape Is Associated With Improved Survival in Adults With HIV-Associated Meningitis Jayne P Ellis 1 , Biyue Dai 2 , Laura Nsangi 3 , Gila Hale 3 , Emmanuel Mande 4 , Jane Gakuru 3 , Enock Kagimu 3 , Timothy Mugabi 3 , Suzan Namombwe 3 , Derrick Kasozi 3 , Sara Kimuda 3 , Asmus Tukundane 3 , David B. Meya 3 , David R. Boulware 2 , Fiona Cresswell 5 1 London School of Hygiene & Tropical Medicine, London, United Kingdom, 2 University of Minnesota, Minneapolis, MN, USA, 3 Infectious Diseases Institute, Kampala, Uganda, 4 Infectious Disease Institute, Kampala, Uganda, 5 Brighton and Sussex Medical School, Brighton, United Kingdom Background: Cryptococcal meningitis and tuberculous meningitis (TBM) remain the most common causes of HIV-associated meningitis, accounting for >20% of AIDS-related deaths globally. Acute mortality associated with these infectious meningitides remains devastatingly high (25-50%), even in the context of clinical trials. We hypothesised that cerebrospinal fluid (CSF) HIV viral escape may contribute to central nervous system (CNS) damage and be associated with increased mortality. Methods: We conducted a cohort study of HIV-positive Uganda adults with suspected meningitis in Kampala, Uganda. We performed baseline paired plasma/CSF HIV viral load (VL) testing (Xpert; Cepheid, Sunnyvale, CA, USA). We determined the prevalence of CSF HIV viral escape, defined as per the consensus definition of presence of quantifiable HIV in the CSF at a concentration above that in plasma, and investigated for associations with mortality using Cox regression. Participants were followed through to hospital discharge, or until week-18 if recruited into a subsequent randomised controlled trial. Results: We recruited 152 adults, 47% were male, median CD4 was 59 (IQR 14-132) cells/mcL, 41% were receiving antiretroviral therapy (ART) at time of presentation. The majority (48%, 73/152) had cryptococcal meningitis, 32% (49/152) had definite/probable TBM, 20% (30/152) suspected "other" meningitis. CSF HIV viral escape was present in 30% (46/152) overall; it was strongly associated (p<0.001) with higher CSF white cell count (102 vs. <5 cells/mcL); and shorter duration of ART (16 vs. 144 days). Amongst those on ART <100 days, CSF HIV viral escape prevalence was 60%. CSF HIV viral escape was associated with improved 18-week survival with an unadjusted Hazard Ratio 0.41 (95%CI, 0.18 – 0.92, p=0.031). CSF viraemia alone was not associated with survival (unadjusted Hazard Ratio 1.04, 95%CI 0.52 – 2.09, p=0.9). Conclusion: In our HIV-associated meningitis cohort, CSF HIV viral escape was common, especially amongst participants recently initiated on ART. As HIV viral replication suppresses more slowly in CSF than plasma, in such cases it is possible that with longer ART duration the CSF would also suppress. Given the observed associations with CSF pleocytosis and improved survival, in the context of HIV-associated meningitis, CSF HIV viral escape is likely a by-stander phenomenon and an indicator of effective host immune response with trafficking of monocytes and CD4 lymphocytes containing HIV RNA into the CNS.

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Poster Abstracts

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Recent ART Initiation and Mortality Risk in HIV-Associated Cryptococcal Meningitis Melanie Moyo 1 , Newton Kalata 1 , James Jafali 1 , David S. Lawrence 2 , Síle Molloy 3 , Henry C. Mwandumba 1 , Johnstone J. Kumwenda 4 , Thomas S. Harrison 3 , Joseph N. Jarvis 2 , for AMBITION-cm and ACTA 1 Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi, 2 London School of Hygiene & Tropical Medicine, London, United Kingdom, 3 St George's University of London, London, United Kingdom, 4 University of Malawi, Blantyre, Malawi Background: Over half of patients diagnosed with cryptococcal meningitis are ART-experienced. The impact of recent ART initiation on outcomes in PLHIV who present with cryptococcal meningitis, and how to optimally manage ART, are unknown. We hypothesised that patients presenting with cryptococcal meningitis following very recent ART initiation (within 14 days) were at higher risk of mortality than ART-naïve individuals or those on ART for longer periods, and that ART interruption reduces this excess mortality. Methods: We analysed data from the ACTA and AMBITION trials to assess whether patients diagnosed with cryptococcal meningitis within 14 days of ART initiation were at higher risk of mortality, and to evaluate the impact of ART interruption on mortality. ART interruption was only performed at clinicians' discretion in the AMBITION trial. Participants were grouped according to ART status and duration of ART. A generalized linear model was used to assess differences in mortality rates between groups. Results: 1484 individuals were included, 707 (48%) not on ART and 777 on ART. ART timing data were available for 649 ART-experienced participants; 18% (120/649) initiated ART 14 days or less prior to diagnosis of CM. Patients who had initiated ART within 14 days had higher CD4 counts, and higher fungal burden than those on ART for over 14 days. 2-week mortality risk was 21.7% (95% CI 14.3-29.0%) in those on ART for 14 days or less, 13.8% (95% CI 7.9-19.8%) on ART for 15-60 days, and 7.6% (95% CI 2.2-13.0%) on ART for 61 days-6 months, increasing to 16% (95% CI 12.2-20.4%) in those on ART for more than 6 months (compared to 16% in those not on ART). Similar mortality trends were seen

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