CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

979

Epigenetic Changes With T. gondii in Brains of People With HIV and Their Possible Link to Gliomas Megha S Srivatsa BS 1 , Momtahina Tahmida 1 , So Youn Shin 2 , Sara Gianella Weibel 1 , Ajay Bharti 1 , Scott L. Letendre 1 , Ronald Ellis 1 , David Moore 1 , Sarah LaMere 1 1 University of California San Diego, La Jolla, CA, USA, 2 Catholic Kwandong University, Gangneung-si, South Korea Background: Toxoplasma gondii , a zoonotic parasite, poses risks for people with HIV (PWH). Although its clinical impact is minimal in immunocompetent hosts, U.S. seroprevalence studies show a 20-30% infection rate. The parasite forms bradyzoites in brain and muscle tissue that can reactivate when CD4+ T cell counts drop in PWH, leading to severe disease. Additionally, T. gondii alters epigenetic pathways in brains of rodents, causing behavioral changes, and its seropositivity in humans is associated with neurobehavioral disorders and adult glioma development. Methods: To investigate the epigenetic effects of T. gondii in the brains of PWH, we conducted a pilot case-control study comparing DNA methylation of CpG dinucleotides in the frontal cortex and basal ganglia of four PWH with confirmed latent T. gondii infection (via ELISA, histopathology, or quantitative PCR) to four IgG seronegative PWH without documented infection. Two of the participants self-reported prior T. gondii encephalitis. Brain tissues were obtained from the California NeuroAIDS Tissue Network (CNTN). We performed reduced representation bisulfite sequencing and assessed differential DNA methylation after deconvolution using Limma. Genes of interest were further analyzed for expression changes and correlation with survival in glioblastoma (GBM) using the Gene Expression Profiling Interactive Analysis (GEPIA). Results: Participants were all virally suppressed non-hispanic caucasian cisgender men with an average age of 50 years (range 30-75) and average CD4+ T cell count of 56 cells/uL (range 27-87) at time of death. In basal ganglia, we identified 63 differentially methylated (DM) sites, with 13 up and 50 down, and in frontal cortex, we found 71 DM sites, with 37 up and 34 down (FDR <0.1, mean difference ≥ ±15%). 70% of DM sites were located in gene bodies, where DNA methylation is positively correlated with gene expression. Notably, approximately half of these genes are associated with gliomas, and expression changes in several of them correlate with decreased survival in GBM ( Figure 1 ). Conclusions: The epigenetic changes in human brains infected with T. gondii suggest that the parasite may influence DNA methylation as in other mammals. The correlation between differentially methylated genes and expression changes linked to GBM points to a potential connection between T. gondii infection and brain tumor development. These findings underscore the need for comprehensive prevention strategies against T. gondii for at risk populations. Factors Associated With Virologic Suppression in People Living With HIV and Tuberculosis in Brazil Ronaldo Coelho 1 , Lara E. Coelho 2 , Célia L. Szwarcwald 2 , Cristina Pimenta 2 , Sandra Wagner Cardoso 3 , Valdilea Gonçalves Veloso 3 , Beatriz Grinsztejn 3 , Draurio Barreira 1 , Nathalie De Castro 4 1 Brazilian Ministry of Health, Brasília, Brazil, 2 Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, 3 Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil, 4 Hôpital Saint-Louis, Paris, France Background: Data from national programs are key to evaluate antiretroviral therapy (ART) virologic effectiveness in real-life settings, especially in people with HIV (PWH) receiving treatment for tuberculosis (TB) . The objective of the present study was to evaluate factors associated with virologic suppression within the Brazilian national HIV/TB program. Methods: A retrospective cohort study was conducted from January 2016 to June 2022, including all adult Brazilian PWH who started ART within 5 months before and 6 months after TB diagnosis. We excluded participants without HIV-1 RNA available. Virologic success was defined as HIV-1 RNA< 50 copies/mL 1 year after ART initiation (window 9-18 months). We assessed determinants of virologic suppression using a multivariate logistic regression analysis. Results: 13,997 PWH treated for tuberculosis were included in the present analysis. At ART initiation, median age was 36 (IQR: 29-45) years and 21.7% were females; median CD4+ T-cell count and HIV-1 RNA were 125 (IQR: 48-278) cells/mm 3 and 5.1 (IQR 4.2-5.7) log 10 copies/mL, respectively. 6,531/13,997 (46.7%) participants started dolutegravir, 2,439/13,997 (17.4%) raltegravir, 4694/13,997 (33.5%) efavirenz. One year after ART initiation, The figure, table, or graphic for this abstract has been removed.

8,206/13,997 (58.6%) participants achieved virologic suppression overall. In the multivariate analysis, TB diagnosis before ART initiation (OR=1.37; 95%CI:1.06 1.77), higher CD4+ T-cell count (CD4≥350/mm 3 ) (OR=1.81; 95%CI:1.55-2.13), HIV-1 RNA <100,000 copies/mL (OR= 1.57; 95%CI:1.38-1.79) and dolutegravir use (OR=1.25; 95%CI:1.11-1.40) were all positively associated to virologic suppression. Factors that were negatively associated to virologic suppression were younger age (18-24 years) (OR=0.79; 95% CI: 0.68-0.93), male sex (OR=0.86; 95%CI: 0.76-0.97) and lower educational level (less than 9 years of schooling) (OR=0.71; 95%CI: 0.64; 0.79). Conclusions: In this analysis from the Brazilian national HIV/TB program, we found that initiating dolutegravir-based regimen was associated with virologic suppression 1 year after ART initiation in PWH treated for TB. Markers of HIV advanced disease and social vulnerability were negatively associated with ART effectiveness, which emphasizes the need to offer person-centred interventions to most vulnerable populations. Recent Trends in Opportunistic Infections at ART Initiation in the NA-ACCORD of IeDEA, 2017-2021 Jonas Kulakauskas 1 , Kate Buchacz 2 , John T. Brooks 2 , Jennifer O. Lam 3 , M. John Gill 4 , Michael Horberg 5 , Maile Karris 6 , Emily C. Williams 7 , Kathleen McGinnis 8 , Catherine Lesko 1 , Richard Moore 1 , Keri N. Althoff 1 , for the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA 1 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 2 Centers for Disease Control and Prevention, Atlanta, GA, USA, 3 Kaiser Permanente Northern California, Oakland, CA, USA, 4 University of Calgary, Calgary, Canada, 5 Kaiser Permanente Mid-Atlantic States, Rockville, MD, USA, 6 University of California San Diego Medical Center, La Jolla, CA, USA, 7 University of Washington, Seattle, WA, USA, 8 VA Pittsburgh Healthcare System, Pittsburgh, PA, USA Background: Understanding the prevalence and consequences of opportunistic infections (OIs) at antiretroviral therapy (ART) initiation remains critical for informing HIV testing and care strategies that reduce the likelihood of late presentation for care. We assessed trends in OIs at ART initiation and their association with 1-year survival in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) Methods: We included adults (≥18 years) with detectable viral loads (>200 copies/mL) initiating ART in the NA-ACCORD from Jan 2017 to Dec 2021. OIs at ART initiation were defined as diagnoses six months prior to two weeks after ART initiation. Annual trends in prevalence of OIs were examined. We estimated the 1-year cumulative incidence of death by OI at ART initiation (with 95% confidence intervals [CI]), and calculated crude (HR) and adjusted hazard ratios (aHR) with 95% CI using Cox proportional hazards models. The adjusted model included age, sex, race and ethnicity, HIV acquisition risk group, HIV viral load, and CD4 count at ART initiation. Results: Among 6,923 people with HIV (PWH) starting ART, 25% were >50 years, 15% female, 71% non-White or Hispanic, 41% men who have sex with men, 27% with CD4 <200 cells/mm 3 and 91% used integrase inhibitors). The prevalence of OIs ranged from 4.7%-6.5% from 2017-2021 (Figure). Among those with an OI at ART initiation (n=374), Pneumocystis pneumonia was most common (44%) followed by esophageal candidiasis (23%). We observed 94 deaths in the first year after ART initiation. The 1-year cumulative incidence of death in those with (vs. without) an OI was 5.5% [CI 3.5%, 8.3%] vs. 1.3% [CI 1.0%, 1.6%]. There was a 4.5-fold increase in the risk of death among those with vs. without an OI at ART initiation in crude models (HR=4.55 [CI 3.09, 7.10]), and in the adjusted model (aHR=1.85 [CI 1.03, 3.34]). Conclusions: From 2017 to 2021, a low (≈5%) but persistent proportion of PWH in the US and Canada are starting ART with an OI, reflecting delayed ART initiation. There is substantially increased mortality risk in the first year after ART initiation among those with (vs. without) an OI. Test and treat strategies focusing on those at highest risk for delayed ART initiation may assure optimal care for persons presenting with OIs to minimize mortality.

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Poster Abstracts

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CROI 2025 310