P513: Project GIVE: Expanding genetic testing to underserved areas in the Rio Grande Valley using an EHR-agnostic tele-engagement platform

Introduction Providing an accurate genetic diagnosis to children in a timely manner is crucial for providing appropriate medical interventions, counseling families about recurrence risks, and addressing the psychosocial and financial challenges that are known to be associated with diagnostic odysseys. Unfortunately, underserved and under resourced areas across the nation have poor access to genetic testing. There is a significant disparity in access to genomic healthcare in the Rio Grande Valley (RGV) along the Texas-Mexico border, which has a population of about 1.4 million residents and no local full-time genetics provider. Over 94% of the population in the RGV is Hispanic, 34% of individuals are uninsured, and upwards of 40% of children in these four counties live in poverty. A lack of expertise of the frontline healthcare providers in identifying individuals in need of a genetics referral and the limited pool of highly trained and qualified board-certified geneticists in the region impedes patient pathways to receive timely genetics evaluation and testing. Project GIVE is an NIH-funded research study at Baylor College of Medicine and University of Texas Rio Grande Valley (UTRGV), initiated in February 2022 that was designed to change the current clinical practice in the region. By leveraging Consultagene, a cutting-edge EHR-Agnostic Tele-Engagement Platform, we can provide timely genetic evaluation and whole genome sequencing (WGS) to improve genetic health of less resourced children in the RGV. Additionally, we improve genetics expertise among frontline healthcare providers in the RGV through CME events that cover various genetics concepts. Methods Frontline providers – including physicians, nurse practitioners, developmental therapists, and medical assistants – refer patients directly to Project GIVE through the HIPAA compliant virtual Consultagene portal (www.consultagene.org). Families accepted into the study meet with the study’s bilingual research coordinator at the UTRGV Specialty Clinic for a virtual genetic evaluation with the BCM geneticists and genetic counselor (“Visit 1”). Buccal samples for trio GS are sent to Baylor Genetics, and “Visit 2” is scheduled when results are available. Return of results counseling is provided, with follow-up recommendations as needed. Patients are longitudinally followed for 1 year. Clinical Sequencing Evidence-Generating Research (CSER) surveys are utilized at all study visits to collect demographic information and assess study outcomes. In addition, two in-person CME conferences have been delivered to improve genomic competency of the frontline providers. Surveys were administered before and after the CME event to assess the impact of the CME event on comfortability with genetics concepts. Data were also collected regarding clinic demographics and access to care factors. Results To date, 147 families have been referred through Consultagene, 102 were accepted, and 49 families have completed Visit 1. Most families identify as Hispanic/Latino (97%), and about half have an annual household income of less than $20,000. WGS results have been returned to 38 families. Thirteen children received a diagnosis or partial diagnosis (34%). We are exploring potential new gene-disease associations for three of our participants with negative WGS. Preliminary results from surveys show that families feel satisfied with WGS results and the use of telemedicine for return of results. Attendees of the CME events reported that they struggled knowing when to refer patients and how to interpret genetic results. They also report challenges with accessing medical records for patients with complex diseases. Providers reported increased comfortability with several genetic concepts post-CME. Conclusion Project GIVE addresses genomic health disparities in under-represented populations by offering virtual genetic evaluation and WGS to pediatric patients with rare diseases. We believe that our model of integrating community engagement and using an advanced virtual platform can be replicated in other disadvantaged areas that lack genetic professionals and resources to improve genomic health of children

A Comparative Study of the KARVI Scale and ASQ-3 Developmental Screening Tools

Developmental screening is essential for identifying children at risk of neurodevelopmental delays. It is particularly useful when assessing neurodevelopment in preterm infants as they are at an increased risk for delay when compared to full-term infants. The American Academy of Pediatrics recommends the use of these tools to reduce the risk of missed detection by using physician judgment alone. Birth to Five: Watch Me Thrive! is a federal program that further emphasizes the importance of using developmental screening tools and provides a guide of research-based tools that have been approved in the United States. The Ages and Stages Questionnaire is one of these tools. The ASQ is implemented as questionnaires that assess five areas of neurodevelopment and can be completed by parents or caregivers. The purpose of this study is to evaluate the performance of the KARVI scale in the assessment of neurodevelopment in comparison to the ASQ. To evaluate this, the KARVI scale and ASQ-3 will be administered during well-child visits during the first year of life. The study aims to assess the effectiveness and ease of use of the KARVI scale in identifying children at risk for developmental delay when compared to the ASQ

Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy: Collaborative Analysis of Cohorts of HIV-1-Infected Patients

Background: The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods: We analyzed data on 20,379 treatment-naive HIV-1- infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results: Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count 350 cells/μL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions: Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART

A highly virulent variant of HIV-1 circulating in the Netherlands.

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log <sub>10</sub> increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence

Human immunodeficiency virus continuum of care in 11 european union countries at the end of 2016 overall and by key population: Have we made progress?

Background. High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods. A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results. We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions. The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control