bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-541. PD-1 expression impacts cardiovascular risk in naïve PLWH (people living with HIV), undergo suppressive ARV
Authors: Aksak-Wąs Bogusz J , Parczewski Miłosz , Skonieczna-Żydecka Karolina , Niedźwiedzka-Rystwej Paulina 
Published: January 2025

Abstract

Background
Human Immunodeficiency Virus (HIV) infection leads to progressive immune dysfunction, among others mediated through the PD-1/PD-L1 pathway. This study aims to assess the impact of ARV therapy on PD-1 expression and SCORE 2 changes in patients over a twelve-month observation period.

Immunofenotype trends in analysed population.

Methods
This observational study evaluated 58 PLWH undergoing standardized ARV therapy according to national guidelines, obtaining viral suppression. Initial and twelve-month follow-up assessments included measurements of SCORE 2, as well as PD-1 expression, and lymphocyte subsets (CD4+, CD8+, and CD4+/CD8+ ratio) using flow cytometry. Wilcoxon signed-rank tests analyzed within-subject changes in these parameters. Principal Component Analysis (PCA) was employed to reduce dimensionality and identify the major axes of variance in the data (delta for all measures) with ARV type as grouping variable. To determine whether the clusters observed in the PCA scatter plot reflect statistically significant differences among the treatment groups, an Analysis of Variance (ANOVA) was conducted on the scores of the first two principal components.
Figure 1
The scatter plot of the first two principal components

Results
There were statistically significant alterations in percentages of CD4+/CD8+ ratio, CD3+, CD4+ along with CD4+ PD-1 and PD-L1 found, all elevated at endpoint. CD19+ was significantly elevated after twelve-month period, as well. Data is displayed in Table 1. We found that the change in these parameters was not dependent on ARV type. SCORE 2 at endpoint correlated positively with CD4+PD1 change (r=0.372; p=0.011), but the parameter change was not dependent on ARV therapy (p &gt;0.05). In PCA analysis, the first principal component captured 22.6% of the total variance, while the second accounted for 20.7%. The scatter plot (figure 1) of the first two principal components showed that the data points (deltas) are distributed and clustered by treatment groups however the differences are not significantly different (PC1: p=0.684; PC2: p=0.840).

Conclusion
Higher expression of PD-1 in CD4+ cells correlates positively with higher cardiovascular risk calculated with SCORE 2, reason for elevated PD1 and PD1-L in ARV treated individuals in comparison to baseline evaluations requires further analysis.

Disclosures
Bogusz J. Aksak-Wąs, MD. PhD. ID Specialist, Gilead Sciences: paid lectures|GSK: paid lectures Miłosz Parczewski, Prof. MD. Phd., Gilead Sciences: Advisor/Consultant|Janssen: Advisor/Consultant|MSD: Advisor/Consultant|ViiV: Advisor/Consultant Karolina Skonieczna-Żydecka, Prof., Sanprobi sp. z o.o. sp. k.: Advisor/Consultant|Sanprobi sp. z o.o. sp. k.: Grant/Research Support|Sanprobi sp. z o.o. sp. k.: Honoraria
P-560. Evaluating the Use of Long-Acting Lenacapravir among Treatment-Experienced Adults with HIV in a Large Community-Based Clinic Network
Authors: Altamirano Jessica A , Shukla Prerak , Barnett Steven K 
Published: January 2025

Abstract

Background
Lenacapravir (LEN) is the first-in-class long-acting capsid inhibitor approved by the FDA in December 2022 for the treatment of multi-drug resistant HIV in adults. It is administered by subcutaneous injection every six months in combination with other antiretrovirals (ARV). It is indicated for heavily treatment-experienced people with HIV (PWH). We assessed the use of long-acting LEN within the CAN Community Health Network.

Methods
A retrospective analysis of electronic medical records within the CAN Community Health Network of 23 clinics located throughout six US states. People with HIV who received one or more injections of LEN for treatment between December 2022 and April 2024 were included. Demographic characteristics, HIV viral load, CD4 count and composition of pre-LEN ARV regimens were studied.

Results
Twenty-four PWH were identified as receiving one or more injections of LEN between December 2022 and April 2024. The median age was 58 years; 79% were male, 67% White and 71% Non-Hispanic (Table 1). Mean number of injections received was 2. Pre-LEN HIV VL was &gt;50 copies/mL in 8 PWH (33%) and pre-LEN HIV VL was &lt; 50 copies/mL in 16 PWH (67%). Five PWH (21%) had a pre-LEN CD4 count &lt; 200 and 19 PWH (79%) had a pre-LEN CD4 count &gt;200. Post-LEN HIV VL decreased in all eight patients with HIV VL &gt;50 copies/mL (Table 2).
Pre-LEN ARV regimens included a median of 4 active agents with 92% of them containing integrase inhibitors (INSTIs), 71% NRTIs and 58% protease inhibitors (PIs) (Table 3). Reasons for switching to a LEN-combination regimen in those with HIV VL &lt; 50 included: simplification, side effects or intolerance to oral ARVs and non-adherence. Three (13%) patients stopped LEN due to injection site reactions (ISRs), 1 patient (4%) stopped due to side effects, 2 patients (8%) were lost to care and 1 patient (4%) was switched to an oral alternative due to travel.

Conclusion
The majority of PWH who were switched to LEN-combination regimens were older males with HIV VL &lt; 50 copies/mL. Reasons for switching included simplification, side effects to other ARVs and non-adherence. Of those with HIV VL &gt; 50 copies/mL prior to switching to a LEN-combination regimen, all had a decrease in their HIV VL. The most common reason for discontinuation was ISRs. Sample size was small and a longer duration of follow-up is needed.

Disclosures
Jessica A. Altamirano, MD, FIDSA, Gilead Sciences: Speaker's Bureau
P-603. Potential Public Health Impact of Respiratory Syncytial Virus (RSV) Vaccines for Prevention of RSV Among Older Adults in the United States
Authors: Averin Ahuva , Sato Reiko , Chilson Erica , Atwood Mark , Quinn Erin 
Published: January 2025

Abstract

Background
Two United States (US) Food and Drug Administration-approved vaccines are recommended by the Advisory Committee for Immunization Practices for prevention of lower respiratory tract disease (LRTD) due to respiratory syncytial virus (RSV) among US adults aged ≥ 60 years and another vaccine for adults is under regulatory review. We evaluated the potential public health impact of vaccines for prevention of RSV-LRTI in older adults.

Methods
A cohort model was employed to depict clinical outcomes and economic costs of RSV-LRTD over two years with use of alternative vaccines (ie, Pfizer’s RSVpreF, GSK’s RSVpreF3, Moderna’s mRNA-1345 respectively, vs no intervention) among a cohort of 2.4M adults aged ≥ 60 years in a hypothetical US health plan with 10M beneficiaries. Clinical outcomes were projected (monthly) based on age, comorbidity profile (ie, with vs without chronic or immunocompromising medical conditions), RSV-LRTI disease rates (requiring hospitalization [H], emergency department [ED], or physician office/hospital outpatient care [PO/HO]), calendar month, case fatality rates (RSV-H only), and vaccination status (23.6% uptake in October of model year 1 only). Initial vaccine effectiveness (VE) and waning of VE was derived from published or presented Phase III clinical trial data. Economic costs were generated based on cases and corresponding unit costs.

Results
Without use of RSV vaccine, 14,687 hospitalizations, 11,201 ED encounters, 132,472 PO/HO visits, and 1,230 RSV-related deaths are projected to occur over two years. Pfizer’s RSVpreF would result in a 22,301-case reduction (RSV-H: 2,713; RSV-ED: 2,069; RSV-PO/HO: 17,519) and 227 fewer deaths; total medical care costs would be lower by $86.0M (RSV-H: $64.2M; RSV-ED: $7.4M; RSV-PO/HO: $14.4M) (Table). GSK’s RSVpreF3 would reduce cases by 16,183, deaths by 205, and medical care costs by $76.8M. Moderna’s mRNA-1345 would reduce cases by 9,357, deaths by 112, and medical care costs by $43.2M (based on single-season efficacy data).

Conclusion
RSV vaccines have the potential to substantially reduce the clinical and economic burden of RSV-LRTI in older adults. Of the three vaccines, Pfizer’s RSVpreF would provide the greatest benefit due to its high 2-year efficacy.

Disclosures
Ahuva Averin, MPP, Pfizer Inc: Advisor/Consultant Reiko Sato, PhD, Pfizer Inc: employee|Pfizer Inc: Stocks/Bonds (Private Company) Erica Chilson, PharmD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds (Public Company) Mark Atwood, MS, Pfizer Inc: Advisor/Consultant Erin Quinn, BS, Pfizer Inc: Advisor/Consultant
P-633. Implementation and Uptake of Nirsevimab within Nemours Children’s Health Delaware Healthcare System
Authors: Mann Sara , Mason Matt , Rellosa Neil , Ravin Karen 
Published: January 2025

Abstract

Background
Nirsevimab, the first FDA approved monoclonal antibody to protect against Respiratory Syncytial Virus (RSV), became available for the 2023-2024 RSV season. Distribution of nirsevimab was affected by cost and a supply shortage, limiting overall uptake. Nemour’s Children’s Hospital in Delaware (NCH) implemented several strategic measures to promote immunization despite these barriers, including educational series and periodic communication of regional supply chain status. The purpose of this project was to analyze characteristics of patients who received nirsevimab at NCH and corresponding trends over the 2023-2024 season.

Methods
We report descriptive summaries of patients who received nirsevimab at NCH from October 2023 to March 2024. Variables analyzed included age, timing of immunization, clinical site and setting, race, sex, insurance status, and state where the patient received the immunization (PA or DE). We compared the distributions of these characteristics by vaccination month using chi-square tests.

Results
1,842 infants received nirsevimab, most of which were under 8 months of age (95.7%) at time of immunization (Table 1). Nirsevimab uptake varied by month (Figure 1), with most patients receiving the immunization in November and December. The distribution of immunizations across visit type (outpatient/inpatient, p&lt; 0.001), insurance type (public/private, p&lt; 0.001), and state (DE/PA) varied significantly across months. The distributions of patient-reported sex and race did not vary significantly by month (Table 2).

Conclusion
Unpredictable supplies of nirsevimab and varying immunization strategies among clinic sites affected distribution and uptake among patients. Some clinics were faced with prioritizing high-risk populations or were restricted by patient insurance policies. These challenges resulted in differing populations having access to nirsevimab based on time of year. Further efforts can focus on unifying immunization promotion techniques and identifying ways to ensure equitable distribution to our target populations.

Disclosures
All Authors: No reported disclosures
P-638. Impact of Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Screening on Antimicrobial De-escalation in Patients Admitted with Community-Acquired Pneumonia
Authors: Deshpande Abhishek , Schulte Rebecca , Walker Ramara E , Pallotta Andrea , Wang Ming , Klompas Michael , Haessler Sarah , Rothberg Michael 
Published: January 2025

Abstract

Background
Methicillin-resistant Staphylococcus aureus (MRSA) is an important yet uncommon cause of inpatient community-acquired pneumonia (CAP). While the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines recommend rapid MRSA nasal screening to guide anti-MRSA antibiotic (abx) therapy when MRSA CAP is suspected, guideline adherence and its impact on abx use is unclear. We aimed to assess the prevalence of MRSA screening and its effect on abx de-escalation in inpatients with CAP.

Methods
This retrospective cohort study analyzed adult admissions for CAP across 12 U.S. hospitals from November 2022 - January 2024. Anti-MRSA abx utilization and MRSA screening was assessed in both ICU and non-ICU patients. De-escalation was defined as stopping all anti-MRSA agents within 48 hours of the first dose. We compared abx de-escalation rates of patients started on empiric anti-MRSA between those screened vs those not screened. Propensity score adjustment methods were employed to assess the association between MRSA screening and anti-MRSA antibiotic de-escalation, calculating the odds ratio (OR) for de-escalation. Positive and negative predictive values of MRSA screening were also calculated.

Results
Of 12,232 CAP hospitalizations, 1886 were admitted to ICU and the rest to medical wards. Thirty percent of non-ICU and 68% of ICU patients were started on anti-MRSA antibiotics within 48 hours of admission. CAP patients started on empiric anti-MRSA antibiotics were significantly more likely than those not started on them to be screened (95% vs. 74% in ICU and 76% vs. 19% outside ICU, p&lt; 0.001 for both). Patients with a negative MRSA screen were more often de-escalated within 48 hours than those with no screening outside the ICU (84% vs. 71%, p&lt; 0.001) and in the ICU (82% vs. 55%, p&lt; 0.001). In propensity-adjusted analysis, screened patients had significantly greater odds of de-escalation compared to those not screened (non-ICU OR: 2.10 95% CI 1.85-2.38; ICU OR: 3.65 95% CI 3.00-4.45). The positive and negative predictive values of MRSA screening were 3.33% and 99.86% in non-ICU, and 6.83% and 99.78% in ICU, respectively.

Conclusion
MRSA screening was strongly associated with abx de-escalation, especially in the ICU. A negative screen had a very high negative predictive value.

Disclosures
Abhishek Deshpande, MD, PhD, AHRQ: Grant/Research Support|Clorox Healthcare: Grant/Research Support Andrea Pallotta, PharmD, Astra Zeneca: Advisor/Consultant|Viiv: Advisor/Consultant Michael Klompas, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|UpToDate: Royalties Michael Rothberg, MD, MPH, Blue Cross Blue Shield: Advisor/Consultant|CRISPER: Stocks/Bonds (Public Company)|Moderna: Stocks/Bonds (Public Company)
P-639. Development of antimicrobial resistance in patients with pneumonia due to P.aeruginosa treated with cefepime or piperacillin-tazobactam
Authors: Pallotta Raneem H , Aitken Samuel L , Pogue jason M , Wangchinda Walaiporn 
Published: January 2025

Abstract

Background
Pneumonia due to P. aeruginosa is associated with significant morbidity and mortality. Recurrent infections and the development of resistance are common. Cefepime (FEP) and piperacillin-tazobactam (TZP) are both first line treatments, yet no studies to date have compared the relative frequency of resistance development in patients treated with these two agents. This study sought to fill in this data gap.Table 1.Baseline Characteristics

Methods
This was a retrospective, single-center cohort study that included adult patients with culture-positive P. aeruginosa pneumonia treated with FEP or TZP admitted to Michigan Medicine. Pneumonia was defined as respiratory signs or symptoms and radiographic evidence of new pneumonia. Patients were eligible if they had therapy started within 24 hours of the index culture and were treated for with FEP or TZP for ≥ 3 days. Patients with unresolved infections, including COVID-19, prior to initiation of the study drug were excluded. Patients with isolates resistant to FEP and/or TZP, regardless of treatment group, were excluded. The primary outcome was development of new resistance to the study drug within 30 days, defined as a repeat culture with non-susceptibility per CLSI criteria to either FEP or TZP on repeat cultures. This was assessed using a Fine-Gray competing risk regression treating death as a competing risk and adjusting for baseline severity of illness, antimicrobial dose, and use of extended infusion.

Results
214 patients (TZP, n=126; FEP, n=88) were included. Baseline characteristics were similar between the two groups, with the notable exceptions of age, creatinine clearance, and Charlson Comorbidity Index (Table 1). Frequency of need for new ICU admission (TZP 27%, FEP 31%; p = 0.65), ventilator-associated pneumonia (25% vs 28%, p = 0.75), and use of extended infusion (14% vs 17%; p = 0.70) were comparable between groups. New resistance to the study drug occurred in 13% of TZP recipients vs 6% receiving FEP (subhazard ratio [sHR] 2.61, 95% CI 0.92 – 8.97, p = 0.07).

Conclusion
We identified statistically similar, but numerically increased risk of new resistance in patients with Pseudomonas pneumonia treated with TZP relative to FEP. These findings may help to inform definitive antimicrobial selection.

Disclosures
Samuel L. Aitken, PharmD, MPH, Basilea: Advisor/Consultant|bioMerieux: Advisor/Consultant|Melinta: Advisor/Consultant|Shionogi: Advisor/Consultant jason M. Pogue, PharmD, Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Venatorx: Advisor/Consultant
P-642. A High Prevalence of Liver Steatosis and Metabolic Syndrome Among Hospitalized Patients with Community-acquired Pneumonia
Authors: Gjurasin Branimir , Krznaric Juraj , Vrsaljko Nina , Papic Neven 
Published: January 2025

Abstract

Background
Community-acquired pneumonia (CAP) is one of the leading causes of morbidity and mortality. While metabolic syndrome has been identified as a risk factor for CAP outcomes, the role of metabolic dysfunction-associated steatotic liver disease (MASLD) in CAP is less clear. This study aimed to investigate the prevalence and severity of MASLD in hospitalized patients with CAP.
Prevalence of metabolic syndrome and MASLD in patients with community-acquired pneumonia

Methods
A prospective observational cohort study (SepsisFAT) included hospitalized adult patients with CAP at three clinical departments at the University Hospital for Infectious Diseases Zagreb. At admission, patients were screened for metabolic syndrome, the degree of liver steatosis was estimated using the controlled attenuation parameter and patients were subesquently diagnosed with MASLD according to current guidelines.

Results
One hundred and fifty patients were included (86 males, median age of 63, IQR 51-73 years). The prevalence of MASLD was 45% (n=68) and metabolic syndrome of 31% (n=46). 43 (29%) patients had insulin resistance, 74 (49%) arterial hypertension, HDL &lt; 1.03 or &lt; 1.29 mmol/L 77 (51%) patients, 46 (31%) triglycerides ≥ 1.7 mmol/L and central adiposity 80 (53%). Steatosis was graded as mild in 21 (14%), moderate in 16 (11%) and severe in 31 (21%) patients, and 20 (13%) patients had fibroleastography &gt; 9.0kPa. The prevalence of MASLD was higher in the severe than non-severe CAP group (43% vs. 34%).

Conclusion
The prevalence of MASLD among hospitalized patients with CAP is higher than estimated in the general population, with the highest prevalence in severe CAP treated at the intensive care unit. This highlights the need for further studies to examine the clinical impact of MASLD on CAP outcomes.

Disclosures
All Authors: No reported disclosures
P-644. Clinical and Sociodemographic Changes in Reported Pertussis Cases, Los Angeles County, 2014-2023
Authors: Foo Chelsea , Washburn Faith , Kim Andrea 
Published: January 2025

Abstract

Background
In 2020, the pertussis national case definition was revised to classify any symptomatic PCR-positive case as confirmed, no longer requiring a cough illness of at least 14 days. The revision intended to improve case ascertainment, but the annual number of pertussis cases reported to Los Angeles County (LAC) Department of Public Health (DPH) has decreased since 2020 due to the pandemic. We sought to describe demographic and clinical differences among pertussis cases reported to LAC before 2020 versus 2020 onwards.

Methods
All confirmed, probable, and suspect pertussis cases reported to LAC DPH from 2014 through 2023 were analyzed. Cases were categorized as pre-2020 (reported 1/1/2014 to 12/31/2019) or post-2020 (reported 1/1/2020 to 12/31/2023). Pearson’s chi-square test was used to assess bivariate associations between report period and case demographics and reported symptoms (paroxysms of coughing, inspiratory whoop, post-tussive vomiting, apnea with or without cyanosis, and cough illness lasting ≥14 days). A logistic regression model was built with report period as the outcome and symptoms and demographics as model covariates.
Event modeled is post-2020 with pre-2020 as reference group.

Results
Of 6,594 cases reported, 391 (5.9%) cases were reported post-2020. Post-2020, the average annual case count decreased 91% from 1,034 to 98. Between time periods, case populations differed with respect to age and ethnicity (p&lt; .001); sex remained similar (p=0.39). Post-2020, median case age decreased from 11 (interquartile range (IQR): 4-16) to 5 (IQR: 2-13). The prevalence of all symptoms decreased post-2020 (p&lt; .001) (Figure 1). In the multivariable model, the association remained significant for cough illness lasting ≥14 days) (odds ratio (OR): 0.47 95% confidence interval (CI): 0.36-0.61) (Figure 2). This finding suggests that among those reporting cough illness lasting ≥14 days, the odds of diagnosis post-2020 versus pre-2020 were lower, after adjustment for age, sex, ethnicity, and other symptoms.

Conclusion
The revised 2020 case definition may have increased case sensitivity in certain populations and among pertussis cases with less severe symptomology. Clinicians may consider PCR testing as soon as pertussis illness is suspected, which could enable sooner public health intervention and prevention of secondary transmission.

Disclosures
Chelsea Foo, MPH, Assertio Holdings: Stocks/Bonds (Public Company)|Bionano Genomics: Stocks/Bonds (Public Company)|eHealth, Inc.: Stocks/Bonds (Public Company)|Johnson & Johnson: Stocks/Bonds (Public Company)