CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

one at week 240 with abnormal NFL had detectable HIV RNA (316 & 20 cps/ml, respectively). Conclusions: CSF samples collected cross-sectionally from pre-ART AHI and post-immediate ART time intervals in RV254 participants exhibited higher NFL levels than PWoH. Abnormal NFL levels were present in 7% of CSF samples collected at week 48 or later, most without detectable HIV RNA, suggesting ongoing neuronal injury in the absence of CSF viral escape. The clinical significance of this finding requires assessment of long-term outcomes in this group.

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High Anticholinergic Burden and Poor Sleep Quality in People With HIV Maria Mazzitelli 1 , Mattia Trunfio 2 , Vincenzo Scaglione 1 , Anna Tozzo 1 , Lolita Sasset 1 , Davide Leoni 1 , Anna Favaro 3 , Anna Maria Cattelan MD 3 1 Azienda Ospedaliera di Padova, Padua, Italy, 2 University of California San Diego, La Jolla, CA, USA, 3 University of Padova, Padova, Italy Background: Anticholinergic burden (ACB) and related effects affect the quality of life of people with HIV (PWH) through a broad range of mechanisms: e.g., increased risk of falls, pleomorphic symptoms, and cognitive decline. To date, no study has investigated whether ACB influences also the quality of sleep (SQ) in PWH. Methods: Cross-sectional single-centre multidimensional assessment of the relationship between sleep metrics (Pittsburgh Sleep Quality Index, PSQI, ≥5 for poor SQ; Insomnia Severity Index, ISI, score ≥15 for moderate/ severe insomnia; Epworth Sleepiness scale, ESS, ≥13 for daily sleepiness) and ACB (ACB scale, ACBS) in 1200 PWH on antiretroviral therapy. Comorbidities, comedications, and mood disorders (General Anxiety disorder-7, GAD7, and Patient Health Questionnaire-9, PHQ9) were also considered. Generalized linear models to investigate these associations were adjusted for relevant factors (e.g., psychiatric diagnoses and treatments, comorbidities). Results: Among the 1200 participants (age 52±12, 74.7% male, 95.5% undetectable viremia, CD4+ T cells 642/µL [483-823]), 11.9%,50.9% and 5.8% had ISI, PSQI, and ESS scores suggesting clinically relevant insomnia, poor SQ, and significant daily sleepiness. Two hundred two (16.8%) participants were on at least one AC drug: 11.0% ACBS=1 and 5.8% ACBS≥2. Increasing ACBS was associated with worsening in all the sleep metrics: the correlations are shown in Fig.1. Polypharmacy (20.4%), multimorbidity (63.7%), depressive mood (13.2%) and anxiety symptoms (20.4%) were also prevalent and associated with both sleep metrics and ACB (Fig.1). In models adjusted by these and other confounding variables (e.g., age, sex, HIV acquisition route, GAD7, PHQ9, use of benzodiazepines, antidepressants), higher ACBS was independently associated with worse scores at both ISI (aβ 0.35 [0.17-0.54], p<0.001) and PSQI (aβ 0.28 [0.16-0.41], p<0.001). Conclusions: These results highlight the complex network between ACB, polypharmacy, multimorbidity, mood and sleep disorders in PWH. However, ACB revealed to be a factor that could disrupt SQ and increase risk of insomnia independently from the underlying clinical indications and other confounding factors in PWH.

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Plasma Microbiome Composition Among Neurobehavioral Phenotypes (NBPs) in People With HIV (PWH) Mohammadsobhan Sheikh Andalibi 1 , Lora Khatib 1 , Bin Tang 1 , Donald R. Franklin 2 , Robert K. Heaton 1 , Rob Knight 1 , Scott L. Letendre 1 , Ronald Ellis 2 1 University of California San Diego, La Jolla, CA, USA, 2 University of California San Diego Medical Center, La Jolla, CA, USA Background: Neurobehavioral disorders and gut dysbiosis continue to occur in treated PWH, but the relationship between the plasma microbiome and NBPs has not been investigated. Plasma microbiome analysis offers unique insights into systemic microbial translocation and immune responses. This study aimed to investigate the association between plasma microbiome composition and neurobehavioral phenotypes in PWH. Methods: 410 PWH who were taking antiretroviral therapy and had plasma HIV RNA ≤ 200 copies/mL underwent comprehensive neuromedical and neurobehavioral assessments and provided plasma for 16S rRNA amplicon sequencing. As previously described, 17 neurobehavioral features, including cognitive domains, depression subscales, and daily functioning, defined 4 NBPs using dimension reduction with a self-organizing maps (SOM) followed by k-means clustering methods: NBP1: healthy (n=187), NBP2: depression dominant (n=94), NBP3: unhealthy in all features (n=55), and NBP4: cognitive impairment-dominant (n=74). Alpha and beta diversity were measured using diversity metrics. Differential species abundance was analyzed using Bayesian Inferential Regression for Differential Microbiome Analysis (BIRDMAn), adjusting for age and gender. Results: Cohort characteristics: mean age 42.7 ± 8.9 years, 16.3% female, 44.9% Black, 59.3% AIDS, mean CD4+ T-cells 467.5/µL. Alpha diversity was lower in NBP2, than in either NBP4 or NBP1 (each p < 0.05). Beta diversity also differed between NBP2 and NBP4 using weighted (p = 0.03) and unweighted UniFrac metrics (p = 0.01). Genus Actinomycetospora and Mycobacterium , Flavobacteriaceae family , and species mucilaginosa were more abundant in people with NBP4 than NBP2, potentially contributing to the observed clinical differences (Figure 1). Conclusions: These findings support a role for the plasma microbiome in modulating brain health in PWH. This may occur in part by modulating immune responses: Mycobacteria can induce proinflammatory immune responses and Flavobacteriaceae produce anti-inflammatory short-chain fatty acids. These results are provocative, but the cross-sectional design limits causal inference. Understanding these complex interactions support development of personalized, microbiome-based interventions to improve brain health in PWH.

Poster Abstracts

CROI 2025 168