bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-433. Impact of Tesamorelin on Cardiovascular Disease Risk Prediction Scores in Phase 3 Studies Treatment Arms: Subanalysis
Authors: Grinspoon Steven K , Fourman Lindsay , Stanley Takara , McGary Colleen , Benkeser David , Cash R Brandon 
Published: January 2025

Abstract

Background
The risk of cardiovascular disease (CVD) is nearly twice as high for persons with HIV (PWH) as the general population. Excess visceral abdominal fat (EVAF), the key characteristic of central adiposity, has also been associated with an increased risk of CVD in PWH. Tesamorelin, a growth hormone-releasing hormone analog, has previously demonstrated significant reductions in EVAF in two phase 3 randomized controlled trials in PWH. Yet, the impact of the reduction of EVAF from tesamorelin on CVD outcomes has been unknown.
Tesamorelin Treatment Effect on CV Risk Score

Methods
To assess this impact, combined datasets from the phase 3 studies’ treatment arms were utilized to calculate 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores at baseline and 26 weeks. A mediation analysis was conducted to characterize the significance of treatment impact via intermediate variables that factor into ASCVD risk prediction changes. Modifiable variables included systolic and diastolic blood pressure, total cholesterol (TC), high-density and low-density lipoprotein (HDL, LDL).
The analysis population included 543 subjects randomized to tesamorelin treatment, 86% of which were male and 22% non-white; the median age was 47 years old. The percentage of subjects on lipid-lowering therapies, hypertension treatment, or diabetic were 46%, 37%, and 18%, respectively.

Results
Although the majority had low CVD risk at baseline, 44% had borderline to high CVD risk. Participants in the tesamorelin treatment arm tended toward a modest reduction in 10-year ASCVD risk prediction with estimated decrease in ASCVD risk of -0.40% (95% CI -0.89%, 0.05%). The reduction in CVD risk was relatively larger among subjects with higher CVD risk at baseline (p=0.038 for overall trend among all participants). Reductions in ASCVD risk score were driven predominantly by reductions in TC, independent of lipid lowering therapies.

Conclusion
In summary, this analysis provides evidence that reductions in excess visceral fat with tesamorelin lead to a significant reduction in forecasted CVD risk in PWH, resulting from reduction in TC even among a group heavily treated with lipid-lowering therapy. Given the increasing prevalence of obesity and central adiposity in PWH, more attention should be given to targeting visceral fat when considering CVD risk management.

Disclosures
Steven K. Grinspoon, MD, Gilead: Grant/Research Support|Kowa: Grant/Research Support|Theratechnologies: Advisor/Consultant|Viiv: Grant/Research Support Lindsay Fourman, MD, Chiesi Farmaceutici: Advisor/Consultant|Chiesi Farmaceutici: Grant/Research Support|Theratechnologies: Advisor/Consultant Takara Stanley, MD, Pfizer: Grant/Research Support Colleen McGary, PhD, Theratechnologies: Employee R Brandon Cash, PharmD, Theratechnologies: Employee
P-448. Contextual assessment and potential barriers and facilitators of a mobile health program to support treatment of tuberculosis and HIV in Kilimanjaro, Tanzania: opportunities for care integration
Authors: Khutsishvili Liza , Fabian Carolin , Ngowi Kennedy , Sariko Margaretha , Wilhelm Krisanta , Mpagama Stellah , Heysell Scott , Boer Marion Sumari-De , Hodges Jacqueline 
Published: January 2025

Abstract

Background
Despite increasing smartphone penetration globally, personalized mobile health (mHealth) care interventions remain largely untapped for people with tuberculosis (TB) in many settings. A smartphone platform adopted to support treatment of human immunodeficiency virus (HIV) in the US was adapted and piloted for HIV/TB care in a distinct urban population, with high usage and improved clinical outcomes. Systematic evaluation of potential contextual influences on mHealth implementation is needed to ensure appropriateness, feasibility, and acceptability of the intervention for HIV/TB care within Kilimanjaro.Table 1:Perspectives on existing HIV and TB care delivery experiences and integration of services

Methods
We conducted semi-structured in-depth interviews at Kilimanjaro Christian Medical Centre and Kibong’oto Hospital with patients (18 y/o+ with drug-susceptible/drug-resistant-TB, with/without HIV, &gt; 1 month on treatment) and providers (e.g. physicians, nurses). Guides were designed using Bury’s Framework for Chronic Illness and the Consolidated Framework for Implementation Research (CFIR). Analysis was performed using a priori open coding/constant comparisons methodology. A preliminary codebook built deductively from frameworks was iterated with inductive codes based on emergent themes.

Results
To date, 12 patient and 12 provider interviews have been conducted; analysis is underway. Specific perspectives demonstrated opportunities for enhancement of HIV/TB care integration (Table 1). Preliminary analysis suggests feature phone access is more common among patients. Additional themes relate to perceptions of an external intervention source (CFIR domain: Intervention Characteristics), compatibility with current provider smartphone access/workload, existing directive nature of patient-provider relationships, and current level of system digitization at sites (workplace internet stability/data access) (Inner Setting).

Conclusion
Analysis to date reveals several prominent themes to consider for adaptation of the intervention: 1) daily life/experiences with TB/HIV 2) determinants of and 3) experiences with TB/HIV care 4) mobile phone ownership, usage 5) perceptions of the intervention within the context and to support 6) home urine testing for personalized dosing of TB medications.

Disclosures
Jacqueline Hodges, MD MPH, Gilead Sciences: Grant/Research Support
P-451. Adherence to Bone Mineral Density Screening Recommendations in Older Adults with HIV
Authors: Martz Madison , Akhverdyan Nazar , Wilson Melissa P , Walker Jacob , Gorvetzian Sarah , Chauhan Lakshmi , Erlandson Kristine M 
Published: January 2025

Abstract

Background
HIV guidelines recommend bone mineral density (BMD) screening by dual-energy x-ray absorptiometry (DXA) for all postmenopausal women and all men ≥50 years. Uptake of these recommendations has been low. This study describes DXA screening practices among people with HIV (PWH) at highest risk for low BMD.

Methods
We conducted a retrospective chart review among PWH aged ≥65 or older who were seen for HIV care at the University of Colorado within the last year. First available and most recent DXA scans were collected; FRAX score was calculated to estimate 10-year risk of major osteoporotic and hip fractures. Demographics and clinical factors were also collected.

Results
We reviewed records of 300 PWH age 65 and older, including 243 (81%) men and 57 (19%) women. The mean age was 69.8 (SD 4.4) years, 62% were non-Hispanic white, 45% had a normal body mass index (18.5-24.9 kg/m2), and 60% reported current/prior tobacco use. 48% had a DXA scan ordered, including 53% of those with previous falls and 54% with prior fracture. Mean age at first DXA scan was 64.9 (SD 6.0) for males and 64.5 (SD 6.4) for women. Of those screened, 13% of women and 27% of men had normal BMD (T-score &gt; -1.0); 45% of women and 53% of men had osteopenia (T-score &lt; -1 to -2.5) and 42% of women and 20% of men had osteoporosis (T-score &lt; -2.5). By FRAX, 10-year probability of major osteoporotic fracture was 9.8% [IQR: 5.7, 13.6] for women and 6.8% [4.7, 11.0] for men. The 10-year probability of hip fracture was 2.2% [0.8, 4.1] for women and 1.4% [0.6, 2.8] for men.

Conclusion
Older PWH are markedly under-screened for low BMD. There was low adherence to screening per current HIV guidelines, even among those with the highest risk. Osteopenia and osteoporosis were common, though FRAX scores suggested only moderate risk. Improved screening for reduced BMD and fracture risk in PWH is urgently needed.

Disclosures
Kristine M. Erlandson, MD MS, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|ViiV: Advisor/Consultant
P-470. CD4 Testing in HIV Care: Uncovering Patterns of Over-Monitoring
Authors: Almaghlouth Nouf K , Komsani Mallikarjun , Shobayo Anuoluwapo , Ayuninjam Diane , Morel Elena , Garland Joseph M , Gillani Fizza S , Flanigan Timothy P 
Published: January 2025

Abstract

Background
In the realm of HIV care, CD4 monitoring guidelines serve as a cornerstone for managing the health and treatment plans of individuals living with HIV. Various authoritative bodies, including the U.S. Department of Health and Human Services (HHS) offer nuanced guidelines tailored to the latest research and clinical best practices. In our study, we aimed to investigate the frequency of unnecessary CD4 testing and assess healthcare providers' comfort level of less frequent monitoring.Figure 1:Healthcare Provider Comfort Levels with Deferring CD4 Count Testing above 500

Methods
We conducted a retrospective cohort study of HIV patients under active care at the Lifespan Immunology Clinic, Miriam Hospital, Providence, Rhode Island, from 2021 to 2023, with undetectable viral loads (&lt; 200 VL) and CD4 counts over 500. Data were extracted from electronic health records, including demographics and clinical measures. Additionally, we conducted qualitative surveys among key healthcare providers to determine adherence to guidelines and to identify any patterns of unnecessary CD4 testing.Figure 2:Awareness of Costs Associated with CD4 Count and HIV Viral Load Testing Among Healthcare Providers

Results
In our first phase of the study, a cohort of 1,929 active unique patients was monitored for their immunological status in 2021. Among these, 1,226 individuals underwent CD4 testing as the event date, with 825 achieving CD4 counts &gt;500. Further analysis highlighted a subgroup of 712 patients who exhibited undetectable viral loads over a three-year span with CD4 counts &gt;500 in 2021. Additionally, 610 of these patients continued to undergo regular CD4 testing after the event date. This group represents approximately 86% of those who were undetectable from 2021 to 2023. In the second phase of the study, a survey involving 40 healthcare providers at the immunology clinic assessed practices in monitoring with CD4 counts &gt;500. The survey revealed 77% were comfortable not performing further CD4 tests, regardless of the patient's viral load status and 90% preferred not testing patients with undetectable viral loads for 1-2 years.

Conclusion
Our study observed significant increasing frequency with unnecessary monitoring of CD4 above 500 with undetectable viral loads. This highlights the importance of implementing future guidelines for minimizing CD4 testing in stable patients, aligning clinical practices and improving outcomes.

Disclosures
All Authors: No reported disclosures
P-471. Clinical and Laboratory Characteristics of the Stockholm HTLV Cohort
Authors: Svensson Anna-Karin , Vesterbacka Jan , Gredmark-Russ Sara , Petropoulos Alexandros , Nordlander Anna , Nowak Piotr 
Published: January 2025

Abstract

Background
The prevalence of HTLV infection in Sweden is presumed to be low, however the impact of demographic changes during the last 20 years on HTLV prevalence is unknown. In our study we describe clinical and laboratory characteristics of patients with HTLV -infection followed at our outpatient clinic at Karolinska University Hospital.

Methods
The clinical and laboratory data has been extracted from medical records of patient with HTLV infection between 2000-2024. We established a database which included demographics, mode of transmission, proviral HTLV load (PVL), occurrence of HTLV-1 associated myelopathy/tropical spastic paraparesis and Adult T cell leukemia (HAM/TSP and ATL), comorbidities and immunological and routine laboratory markers.

Results
We identified 101 patients with HTLV infection followed at our site (80% HTLV-1, 20% HTLV-2). Fifty-tree percent (n=54) were women. The average age in the cohort was 53,6 years (23-81). Twenty-nine percent (n=29) of the patients were born in Sweden, while the rest had other countries of origin (35% Middle east; 17% South America; 11% Africa ). HTLV infection was predominantly diagnosed through contact testing (34%), blood donor screening (32%), and pre-in vitro fertilization screening (32%), while clinical symptom investigation accounted for 12% of cases. Eleven individuals were HIV positive and predominantly co infected with HTLV-2. Of note, within the subset of patients born in Sweden, we identified four cases of mother-to-child transmission (MTCT) of HTLV.
Until January 2024 ten individuals (10%) were diagnosed with HAM/TSP and two individuals with ATL. Patients with HAM/TSP had a higher average PVL as compared to the rest of the cohort (20,9% vs 7,8%).
Furthermore, we conducted a quantitative analysis of regulatory T-cells in 26 HTLV-1 infected patients in peripheral blood using flow cytometry. Fifteen patients (58%) had elevated T-reg percentage (ranging from 12% to 51%) and higher PVL. Notably all three HAM/TSP patients were in the elevated T reg group.

Conclusion
In our cohort, we report a high percentage of patients with HAM/TSP and ATL. Notably, we found four cases of MTCT in patients born in Sweden. We also found a higher abundance of regulatory T-cells in the patient’s group with higher PVL and more prevalent occurrence of symptoms.

Disclosures
All Authors: No reported disclosures
P-482. Evaluating Vitamin B12 Deficiency in People Living with HIV Compared to Metformin Users
Authors: Nguyen Lee , Farihi Bahman , Diamond Catherine 
Published: January 2025

Abstract

Background
Vitamin B12 is a water-soluble vitamin critical for the development and function of the central nervous system, as well as the formation of red blood cells and DNA synthesis. Both HIV and metformin use have been associated with vitamin B12 deficiency. The degree of vitamin B12 deficiency in HV has not been quantified compared to other known causative conditions. Our study aims to describe the incidence of vitamin B12 deficiency in HIV-infected individuals compared to metformin-induced vitamin B12 deficiency. Our secondary goal is to describe the demographics of HIV patients requiring B12 replacement therapy.

Methods
This database study evaluated de-identified medical records from 01/01/2015 to 07/01/2023 at a single large academic institution. We evaluated two study populations: HIV patients and metformin users. For inclusion, both populations required a lab test for vitamin B12 level after starting metformin or the diagnosis of HIV. We defined vitamin B12 deficiency as starting B12 replacement therapy within 4 months of the lab test.

Results
We identified 3,253 HIV and 50,751 metformin-use patients for our study. Among all HIV patients, 717 received a B12 lab test, and 144 (20%, 95% CI 0.173 to 0.232) required replacement therapy. Metformin users had 7773 individuals that received a B12 lab test, and 1187 (15%, 95% CI 0.145 to 0.161) required replacement therapy. The rate of B12 deficiencies was higher among the HIV population (20%) than the metformin (15%), p=0.0007. The relative risk for vitamin B12 deficiency among the HIV population is 1.315 (95% CI 1.126 to 1.536). The number of HIV patients not on metformin with a B12 lab test was 631, and 124 required replacement therapy (19.7%). The HIV population was primarily men (84%), with 50% in the age range of 40-60 years and 63% identified as white.

Conclusion
Vitamin B12 deficiency is a known problem associated with metformin administration and HIV infection. This study identified that our HIV population has higher rates of vitamin B12 deficiency than the metformin group. The cause of this deficiency is unknown. Improved awareness of vitamin B12 deficiency in HIV patients may facilitate improved monitoring and supplementation, which in turn may decrease HIV-associated comorbidities such as dementia and neuropathy.

Disclosures
Lee Nguyen, PharmD, APh, BCPS-AQ ID, BCIDP, Merck & Co: Grant/Research Support
P-483. Late presentation of People Living With HIV in “Treat All” Era in Maputo City, Mozambique
Authors: Chambal Lucia Mabalane , Nilsson Charlotta , Manjate Elias , Tchavana Corssino , Muchangos Vanda dos , Augusto Orvalho , Comiche Esperanca Sevene 
Published: January 2025

Abstract

Background
Advanced HIV disease (AHD), defined as People Living with HIV with a CD4 cell count &lt; 200 cells/mm3 or WHO clinical stage 3 or 4, increases the risk of severe opportunistic infections, hospitalizations, and death. Programmatic data from Mozambique showed a reduction in the prevalence of AHD at ART initiation from 73% to 37% during 2004-2014. Since 2016, Mozambique has adopted the “Treat all” strategy, and data on AHD at presentation for care is limited. We assess the prevalence of AHD in recently diagnosed HIV clients ART naïve.
Relation between Age and Gender and AHD prevalece

Methods
An analysis of baseline data of a prospective cohort study in newly HIV-diagnosed ART naïve at Mavalane Health Centre (MHC) located in a periurban area in Maputo City. April 2021-November 2022, all HIV-1 diagnosed ART naïve above 18 years of age were enrolled. A questionnaire was administered to assess risk factors for HIV infection, and CD4+ T cell counts and HIV viral load were determined.

Results
A total of 1,025 PLHIV were enrolled, of whom 560 (55%) were females, median age of 35 (IQR: 30, 43) years, and mean BMI was 23.7 kg/m2 (SD: 4.48) with 8.1% under 18.5 kg/m2. The overall median CD4 + cell count was 252 (IQR: 140, 421) cells/mm3, with 46.0% (214/465, 95%CI: 41.4-50.7%) and 32.7% (183/560, 95%CI: 28.8-36.7%) of males and females, respectively, below 200 cells/mm3. There was an age-ascending trend (p-value: &lt; 0.001) among females from 15.0% (95%CI: 8.6-23.5%) to 53.7% (95%CI: 43.2-64.0%). There was age dependency among males (p-value: 0.1887). The overall median log10 HIV-RNA was 5.12 (IQR: 4.67, 5.52), 4.41 (IQR: 3.63, 4.94) among AHD and non-AHD, respectively (p-value &lt; 0.001).

Conclusion
This study unveiled a high burden of AHD, showing that even in an era when countries are working on strategies for early HIV diagnosis and treatment to reduce the incidence of HIV and mortality associated with opportunistic infections, clients are still presenting in an advanced stage of the disease.

Disclosures
All Authors: No reported disclosures
P-487. [18F]-labeled J3 Nanobody is a Specific PET Tracer for Molecular Imaging of HIV-1 gp120
Authors: Martinez-Orengo Neysha , Shah Swati , Lai Jianhao , Basuli Falguni , Turner Mitchell , Peiravi Morteza , Sampson Kevon , Swenson Rolf , Maldarelli Frank , Nath Avindra , Lau Chuen-Yen , Hammoud Dima A 
Published: January 2025

Abstract

Background
Targeted molecular imaging of HIV-1 can potentially identify viral reservoirs and provide a better understanding of disease pathogenesis and management. Nanobody-based radiolabeled probes offer several advantages over full antibodies, including smaller size, deep tissue penetration, and high stability. In this study, three fluorine-18 labeled nanobodies targeting the well-conserved CD4-binding site on HIV-1 envelope protein (gp120) were evaluated in gp120-expressing flank tumor models.

Methods
Binding affinities to gp120 protein were determined by bio-layer interferometry. For in vivo PET imaging, an animal model with wild type (WT) and/or gp120-expressing HEK293T cells (gp120+) flank tumors was developed in nude mice. Radiolabeled nanobodies were prepared by an indirect labeling method using 6-fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester (6-[18F]FPy-TFP) prosthetic group. Dynamic PET/CT images up to 60 minutes and static images at 120 minutes were obtained. Tumors were evaluated ex vivo using immunofluorescent staining. Unpaired t test was used for statistical analysis.

Results
J3 nanobody showed higher binding affinity to gp120 compared to 3E3 and B9, with KD values of 1.1nM, 3.4nM, and 23.7nM, respectively. PET/CT imaging revealed selective binding (measured as SUVpeak) to gp120+ compared to WT tumors with J3 (0.64 ± 0.14 vs. 0.29 ± 0.08) and 3E3 (0.61 ± 0.27 vs. 0.22 ± 0.12) but not with B9 (0.21 ± 0.14 vs 0.25 ± 0.12). After 2 hours, J3 and 3E3 had minimal background signal, whereas B9 showed poor ligand clearance and off target binding (Fig. 1). [18F]J3 time activity curves (TACs) from dynamic and static scans showed selective binding to gp120+ tumors compared to WT tumors (Fig. 2). To validate our PET findings, ex vivo gp120 tumor expression was confirmed by immunofluorescence staining. J3 nanobody showed specific immunoreactivity that colocalized with VRC01, an anti-gp120 full antibody (Fig. 3).

Conclusion
We evaluated the binding characteristics of three 18F-labeled nanobodies to gp120+ cells. Overall, J3 nanobody had higher specificity and binding to its target compared to 3E3 and B9, demonstrating a higher potential for non-invasive identification of HIV-infected cells in infected models.

Disclosures
All Authors: No reported disclosures
P-503. Health Care Providers' Experiences with and Perceived Barriers to Implementation of Long-Acting Injectable Preexposure Prophylaxis
Authors: Beideck Elena , Gould Ryan , Krakower Douglas 
Published: January 2025

Abstract

Background
Many patients eligible for preexposure prophylaxis (PrEP) for HIV are not yet prescribed it. Long-acting injectable cabotegravir (CAB-LA) may be a tool to increase PrEP coverage, though its uptake has been limited.

Methods
We conducted an online national survey to evaluate providers’ experiences with prescribing and perceived barriers to implementing CAB-LA. The anonymous survey was administered from 07/2023 to 11/2023 to a convenience sample of providers affiliated with the AIDS Education and Training Centers. We used Fisher’s exact tests to assess for factors associated with availability and use of CAB-LA.

Results
There were 89 total respondents from diverse professions (40% physicians, 60% non-physicians) from multiple regions (61% in the Northeast). Nearly half (46%) reported that at least 10% of their panel was uninsured and most (85%) reported that at least 40% of their panel had public insurance. Among providers, 57% reported their primary clinic site offered CAB-LA. Only 29% had patients on CAB-LA, and 10% had patients who tried CAB-LA and switched to oral PrEP. The most common perceived systems-level barriers to use of CAB-LA were concerns about insurance coverage (84%) and logistic constraints (78%). The most common perceived patient-related barriers were lack of patient requests (71%), concern for missed injections (68%), and cost (64%). The most common perceived reasons for patients to switch off of CAB-LA were burden of appointments (78%), injection site pain (67%) or other side effects (44%), and cost (33%). A majority (67%) reported that lack of training was at least a minor barrier to the prescribing of CAB-LA by providers at their practice site. Rates of CAB-LA availability and providers having prescribed CAB-LA did not vary by provider credentials, region, panel insurance mix, or rates of uninsured patients in providers’ panels (p-values all &gt;0.05).

Conclusion
This study highlights the modest rate of availability and the low rate of prescribing of CAB-LA. This suggests the need for improved strategies to implement CAB-LA, specifically surrounding cost, clinic logistics, patient awareness, and provider education. The rate of providers who have had patients switch off of CAB-LA suggests that patients may benefit from support to ease the burden of appointments and cost.

Disclosures
Douglas Krakower, MD, FluidForm Bio: Stocks/Bonds (Private Company)|Gilead: Grant/Research Support|Matchbox Health: Stocks/Bonds (Private Company)|Medscape: Funding to develop educational content|Merck: Grant/Research Support