BACKGROUND:The Department of Veterans Affairs (VA), the largest integrated HIV care provider in the United States (US), used the HIV Care Continuum to compare clinical care within the VA HIV ...population with the general US HIV population and to identify areas for improvement.
METHODS:National data from the VAʼs HIV Clinical Case Registry were used to construct measures along the Continuum for Veterans in VA care diagnosed with HIV by June 2013 and alive by December 31, 2013. Comparisons were made to recent estimates for the same measures for the US HIV population. Additional comparisons were performed for demographic subgroups of sex, race/ethnicity, and age.
RESULTS:Of 25,480 Veterans diagnosed with HIV, 77.4% were engaged in care compared with 46.3% in the US population diagnosed with HIV (P < 0.001). Seventy-three percent of Veterans diagnosed with HIV received antiretroviral therapy compared with 43% of the US population diagnosed with HIV (P < 0.001). Nearly two-thirds (65.3%) of HIV-diagnosed Veterans had suppressed HIV viral loads compared with 35.0% of the US population diagnosed with HIV (P < 0.001).
CONCLUSIONS:The VA health care system performed better at every stage of the HIV Care Continuum compared with the general US estimates. Comparable high rates with some variation were noted among the demographic groups in the VA cohort. The high viral suppression rate in VA, which was almost double the estimate for the HIV-diagnosed US population, demonstrates that improved outcomes along the HIV Care Continuum can be achieved in a comprehensive integrated health care system.
Abstract
Cytokines and other immune regulatory molecules are critical players in the immune response against cancer. There is growing interest in testing the potential utility of systemic immune ...biomarkers to track cancer progression and to use them as predictors of effective responses to cancer therapy. The central hypothesis guiding this project is that specific immune biomarkers will serve as predictors of effective vs. ineffective immunotherapy in patients with malignant diseases. The objective of this study was to establish baseline of immune markers in patients already started treatment with immunotherapy (n=10) (T), patients starting, but not yet treated (S) with immunotherapy (n=10) and subjects without diagnosed malignant disease (W) (n=10). Blood was collected and plasma was isolated and used in the biomarker (100 markers) analysis using a protein microarray method (RayBiotech). The biomarkers in the three groups were analyzed by Principal Component Analysis, heat map with clustering, and differential expression based on p value, and Significance Analysis of Microarrays (SAM). Although 15 biomarkers were significantly different between S vs. W groups, based on SAM, only seven were found differentially expressed. Similarly, although 10 biomarkers were significantly different between T vs. W groups, based on SAM, only one biomarker was found differentially expressed. Furthermore, SAM revealed that responders (n=4) vs. stable (n=5) subgroup of patients within the T group exhibited 22 differentially expressed biomarkers. Future larger studies will be needed to evaluate whether immune markers will be able to predict effective vs. ineffective responses to immunotherapy and whether they may have therapeutic potential.
LBA501 Background: I-SPY2.2 is a multicenter phase 2 platform sequential multiple assignment randomized trial (SMART) in the neoadjuvant breast cancer setting that evaluates novel experimental ...regimens as first in a sequence (Block A) followed by standard chemo/targeted therapies (Blocks B/C) if indicated. The goal is to achieve a pCR after novel targeted agents alone or in sequence with standard therapies, with the optimal therapy assigned based on the tumor response predictive subtype (RPS). RPS incorporates expression-based immune, DNA repair deficiency (DRD), and luminal signatures with hormone receptor (HR) and HER2 status to subset patients into 6 subtypes: S1: HR+HER2-Immune-DRD-; S2: HR-HER2-Immune-DRD-; S3: HER2-Immune+; S4: HER2-Immune-DRD+; S5: HER2+/non-Luminal; S6: HER2+/Luminal. Methods: RPS S1, S2, S3, and S4 were eligible for assignment to Dato+Durva in Block A. Patients were followed by MRI during treatment (at 3, 6, and 12 weeks after start of Blocks A and B). Predicted responders by MRI and biopsy at the end of Block A or B have the option of going to surgery early; otherwise, they proceed to next treatment Block (B +/- C). Randomization to Block B includes a taxane-based regimen specific to the RPS, and options include S1: paclitaxel; S2 and S3: paclitaxel + carboplatin + pembrolizumab; S4: paclitaxel + carboplatin vs. paclitaxel + carboplatin + pembrolizumab. Patients who did not go to surgery after Block B proceeded to Block C (AC or AC + Pembrolizumab if HR-HER2-). The primary endpoint is pCR. Efficacy is evaluated within each RPS and HR+HER2- and HR-HER2- signatures. To estimate the arm's efficacy as a stand-alone therapy, we use a Bayesian covariate-adjusted model to estimate the pCR rate and compare the posterior distribution to a subtype-specific fixed threshold. This model uses pCR data when available and MRI data when pCR is not. To estimate pCR rate in the context of a multi-decision treatment regimen, we use a Bayesian model based on if and when a pCR occurred in the trial. The posterior is compared to a subtype-specific dynamic control generated from historical I-SPY data. Results: 106 patients were randomly assigned to the Dato+Durva arm between September 2022 and August 2023. The results for Dato+Durva as a stand-alone therapy are summarized in Table. After completion of Block A, 36 patients proceeded to surgery without completing Blocks B/C. Conclusions: Dato+Durva meets threshold for graduation within the RPS S3 subtype based on estimated pCR rate of 72% and warrants further investigation in a larger randomized controlled trial. Clinical trial information: NCT01042379 . Table: see text
Objective. To present the characteristics of the AKT1E117K gene variant and a description of the clinical application in a patient with metastatic breast cancer.Results. 63 y/o woman with Stage IV ...Invasive lobular carcinoma at diagnosis was treated with Palbociclib and aromatase inhibitors (AI). At progression, tissue was sent for comprehensive genomic profiling to Foundation Medicine (FM) which revealed AKT1E17K mutation. In lieu of available clinical data within the patient’s tumor type (HR+ HER2- breast cancer), extrapolated data from the Flatiron Health-FM (FH-FMI) Clinico-genomic Database (CGDB) was dis- cussed at our Molecular Tumor Board (MTB). After multidisciplinary discussion, the consensus recommendation was to start treatment with the combination of mTOR inhibitor everolimus, and AI, exemestane. Patient tolerated treatment without major side effects. By the second clinical visit the patient’s breast showed signs of improvement. PET/CT showed diminished left axillary uptake, decreased right paratracheal lymph node PET avidity, and stable bone disease consistent with a partial response. The most recent office visit in January 2021, breast exam revealed a normal-appearing skin with only faint erythema. All other skin lesions have resolved. Although, the role of AKT1 variant described here is not well defined and therapeutic significance of M-Tor inhibitors not established in metastatic breast cancers, comprehensive approach to this case unraveled new and successful therapeutic option in this patient. Conclusion. This demonstrates that applying available Precision Medicine tools like MTB and real world data sets from patient populations with similar clinical and genomic profiles may provide more options for treatment.
To present the characteristics of the AKT1E117K gene variant and a description of the clinical application in a patient with metastatic breast cancer.
63 y/o woman with Stage IV Invasive lobular ...carcinoma at diagnosis was treated with Palbociclib and aromatase inhibitors (AI). At progression, tissue was sent for comprehensive genomic profiling to Foundation Medicine (FM) which revealed AKT1E17K mutation. In lieu of available clinical data within the patient's tumor type (HR+ HER2- breast cancer), extrapolated data from the Flatiron Health-FM (FH-FMI) Clinico-genomic Database (CGDB) was discussed at our Molecular Tumor Board (MTB). After multidisciplinary discussion, the consensus recommendation was to start treatment with the combination of mTOR inhibitor everolimus, and AI, exemestane. Patient tolerated treatment without major side effects. By the second clinical visit the patient's breast showed signs of improvement. PET/CT showed diminished left axillary uptake, decreased right paratracheal lymph node PET avidity, and stable bone disease consistent with a partial response. The most recent office visit in January 2021, breast exam revealed a normal-appearing skin with only faint erythema. All other skin lesions have resolved. Although, the role of AKT1 variant described here is not well defined and therapeutic significance of M-Tor inhibitors not established in metastatic breast cancers, comprehensive approach to this case unraveled new and successful therapeutic option in this patient.
This demonstrates that applying available Precision Medicine tools like MTB and real world data sets from patient populations with similar clinical and genomic profiles may provide more options for treatment.
Infants acquire maternal antibodies by Fc receptor transcytosis across the placenta during pregnancy. Fc receptors are expressed on immune cells and are important for activation of effector cell ...functions.
In this study, we evaluated Fc receptor engagement and ADCC activity of plasma binding antibodies from human immunodeficiency virus-1 (HIV) -infected mothers and to identify factors that may contribute to protection from HIV vertical transmission.
HIV-specific binding and Fc receptor engagement of plasma antibodies varied between mothers by transmission status and infants by infection status. Non-transmitting (NT) mothers and HIV-uninfected infants had antibodies with higher neonatal Fc receptor (FcRn) and FcγR engagement, as compared to transmitting (T) mothers and HIV+ infants, respectively. A significant inverse correlation between plasma antibody FcRn and FcγR engagement was observed for T mothers, but not NT mothers. Conversely, a significant direct correlation was observed between plasma antibody FcRn and FcγR engagement for HIV- infants, but not for HIV+ infants. Consequently, we observed significantly higher plasma antibody ADCC potency and breadth in HIV- infants, as compared to HIV+ infants. However, no differences in overall ADCC potency and breadth were observed between mothers. FcRn-engagement of HIV-specific antibodies in both mothers and infants predicted a lack of vertical transmission of HIV.
This study indicates that HIV-uninfected infants acquire HIV-specific antibodies with greater Fc receptor engagement and thus, greater ADCC capacity.
Objective:
To understand SARS-CoV-2 transmission in early care and education (ECE) settings, we implemented a Test to Stay (TTS) strategy, which allowed children and staff who were close contacts to ...COVID-19 to remain in person if they agreed to test twice after exposure. We describe SARS-CoV-2 transmission, testing preferences, and the number of in-person days saved among participating ECE facilities.
Methods:
From March 21 through May 27, 2022, 32 ECE facilities in Illinois implemented TTS. Unvaccinated children and staff who were not up to date with COVID-19 vaccination could participate if exposed to COVID-19. Participants received 2 tests within 7 days after exposure and were given the option to test at home or at the ECE facility.
Results:
During the study period, 331 TTS participants were exposed to index cases (defined as people attending the ECE facility with a positive SARS-CoV-2 test result during the infectious period); 14 participants tested positive, resulting in a secondary attack rate of 4.2%. No tertiary cases (defined as a person with a positive SARS-CoV-2 test result within 10 days after exposure to a secondary case) occurred in the ECE facilities. Most participants (366 of 383; 95.6%) chose to test at home. Remaining in-person after an exposure to COVID-19 saved approximately 1915 in-person days among children and staff and approximately 1870 parent workdays.
Conclusion:
SARS-CoV-2 transmission rates were low in ECE facilities during the study period. Serial testing after COVID-19 exposure among children and staff at ECE facilities is a valuable strategy to allow children to remain in person and parents to avoid missing workdays.
Objectives:
Quarantine after exposure to COVID-19 has resulted in substantial loss of in-person learning in schools from prekindergarten through grade 12. Test to Stay (TTS), a strategy that limits ...the spread of SARS-CoV-2 while prioritizing in-person learning, requires substantial investment in resources. The objective of this study was to assess the perceived benefits, barriers, and facilitators of implementing TTS in an urban school district in the Midwest serving primarily Black or African American people with low income.
Methods:
In December 2021, we used a concurrent mixed-methods approach to understand perceived benefits, barriers, and facilitators of implementing TTS by combining quantitative analysis of telephone surveys conducted with parents (n = 124) and a qualitative inquiry involving key informants from the school district and local health department (n = 22). We analyzed quantitative data using descriptive statistics. We used thematic analysis to analyze qualitative data.
Results:
Quantitative findings showed that parents supported TTS because it was convenient (n = 83, 97%) and effective (n = 82, 95%) in keeping students learning in person (n = 82, 95%) and preventing the spread of COVID-19 (n = 80, 93%). Qualitative interviews with informants found that having a clear protocol and assigning staff to specified tasks allowed for successful TTS implementation. However, insufficient staffing and testing resources, parent mistrust of testing, and lack of communication from schools were perceived barriers.
Conclusion:
The school community strongly supported TTS despite the many implementation challenges faced. This study emphasized the importance of ensuring resources for equitable implementation of COVID-19 prevention strategies and the critical role of communication.
Objectives:
Florida ranks highest in the United States among newly diagnosed HIV infections. This ranking reflects the need for investigation of healthcare providers’ knowledge, readiness, ...prescribing behaviors, and perceived barriers to routine HIV testing and pre-exposure prophylaxis.
Methods:
We adapted national questionnaires with questions co-developed with Florida Department of Health to form a 25-item instrument. Questionnaires were distributed to the population of eligible healthcare providers in DeLand, Florida.
Results:
Results from an approximate 20% response rate that encompasses 12 providers demonstrate baseline findings to inform future studies. For example, 75% of respondents were aware of FL Administrative Code 64D-3.042 that pregnant women should receive HIV testing during first and third trimesters. However, 50% of respondents rarely or never offer tests to pregnant women according to practice guidelines. About 75% of respondents strongly agree or agree with willingness to prescribe pre-exposure prophylaxis to high-risk patients, yet 8.3% always or very often prescribe pre-exposure prophylaxis.
Conclusions:
Results convey the importance of and need for greater collaboration between providers and the Florida Department of Health to enhance providers’ knowledge, readiness, and, ultimately, behaviors regarding routine HIV testing and pre-exposure prophylaxis prescription.
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