194 -199). In contrast, the sequence elements that may comprise origins in multicellular eukaryotes are largely unknown. The yeast HMR-E region is both a chromosomal origin of replication and a silencer that represses transcription of adjacent genes through a position effect. The analysis presented here indicated that HMR-E had a novel DNA structure that was more complex than defined for other yeast origins, and thus revealed that there is variation in the structural complexity of yeast origins. In contrast to "simple" yeast origins, the origin at HMR-E consisted of at least three independent subregions that had the capacity to initiate replication. We have termed HMR-E a compound origin to reflect its structural complexity. Furthermore, only one origin within the compound origin was a silencer.

BACKGROUND: Currently available treatments for hemophilia A and B require frequent intravenous infusions. Gene therapy, by contrast, offers the hope of a functional cure through endogenous expression of the factor VIII or factor IX genes. To identify and address practice gaps among healthcare providers who manage patients with hemophilia, a collaboration between the National Hemophilia Foundation (NHF), European Haemophilia Consortium (EHC), World Federation of Hemophilia (WFH), and Medscape Education was established. The objective of the current study is to assess clinicians' needs with regard to understanding the science and mechanism for gene therapy, the different technologies being proposed, identifying candidates for gene therapy, disease areas for which gene therapy is being explored, and the latest data on the potential role of gene therapy in hemophilia A and B. METHODS: A continuing medical education (CME)-certified clinical practice assessment comprising 25 multiple choice questions that measured knowledge, attitudes, and perspectives about gene therapy was developed. The survey instrument was made available online to physicians without monetary compensation or charge. Respondent confidentiality was maintained and responses were de-identified and aggregated prior to analyses. The activity launched on March 03, 2018; data through July 27, 2018 are presented, but data collection is ongoing. RESULTS: At the time of this analysis, 194 physician participants indicated that they actively manage patients with hemophilia. Demographics are presented in Table 1; confidence and attitudes about gene therapy in Table 2. Among hematologists/oncologists (n=54; hem/onc), identified knowledge gaps include, 46% could not identify the liver as the tissue/cell type that is the primary target for gene therapy in hemophilia46% thought that current approaches to gene therapy in hemophilia involved some form of host gene editing39% did not realize that gene therapy strategies only affect somatic cells and not the germline22% thought current gene therapy strategies would prevent or reduce the severity of hemophilia in subsequent generations of patients33% were unable to correctly identify adeno-associated virus (AAV) as the viral vector that is the current basis for the majority of gene therapy trials in hemophilia81% had misconceptions regarding the key characteristics of the AAV vector56% did not recognize that the AAV vector does not routinely integrate into the host genome19% were unfamiliar with the maximum gene cassette capacity of AAV57% were unfamiliar with the results from the pivotal University College London (UCL)/St Jude trial of scAAV2/8-LP1-hFIXcovector in patients with hemophilia B63% were unfamiliar with the clinical trial data for SPK-8011 in hemophilia A67% were unfamiliar with the results at the 12 month time-point for valoctocogene roxaparvovec in hemophilia A trials57% had misconceptions with regard to the causes for and treatment of ALT elevations seen in hemophilia AAV gene therapy trials CONCLUSIONS: Gene therapy has the potential to fundamentally alter the management of hemophilia. This educational activity identified clear deficits about - and attitudes toward - gene therapy among healthcare providers who currently care for patients with hemophilia. Furthermore, the great majority of healthcare providers lacked confidence in their understanding of gene therapy for hemophilia A. These findings will be used to inform the development of educational programs and to prepare providers for anticipated changes to the hemophilia treatment landscape. Disclosures Pasi: Catalyst Bio: Honoraria; Octapharma: Honoraria; NovoNordisk: Speakers Bureau; Bioverativ: Honoraria, Research Funding; Apcintex: Honoraria; Shire: Speakers Bureau; Bayer: Speakers Bureau; Pfizer: Speakers Bureau; Sobi: Honoraria; Biomarin: Honoraria, Research Funding; Alnylam: Honoraria, Research Funding.

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Background Despite therapeutic advances, treatment-experienced HIV patients can present a clinical challenge, even to experienced care providers. Table. Assessment of Educational Effectiveness Methods This study assessed the ability of digital education to improve HIV/ID specialists’ ability to develop tailored strategies for treatment-experienced patients. A CME/ABIM MOC/CE-certified, case-based, educational program was developed. Modeled after the interactive grand rounds approach, a “test then teach” strategy with multiple choice questions was used to elicit cognitive dissonance. Evidence-based feedback was provided following each response. Educational effectiveness was assessed with a repeated-pairs pre-/post-assessment study design; each individual served as his/her own control. A chi-square test assessed changes pre- to post-assessment. P values < 0.05 are statistically significant. Effect sizes were evaluated using Cramer’s V (< 0.05 modest; 0.06-0.15 noticeable effect; 0.16-0.26 considerable effect; > 0.26 extensive effect). The activity launched on a website dedicated to continuous professional development on 09/12/19. Data for this matched-learner analysis were collected through 11/06/19. Results To date, 14,181 HCPs (3128 physicians; 9518 nurses/NPs; 333 PAs; 172 pharmacists) have participated in the activity. Data from the subset of HIV/ID specialists (n=110) who answered all pre-/post-assessment questions during the initial study period were analyzed. Following activity participation, significant improvements were observed in the proportion of HIV/ID specialists who answered all assessment questions correctly (15% pre vs 81% post; P < .0001; V=.356). Improvements were also observed in several specific areas of assessment (Table). Additionally, 44% of HIV/ID specialists indicated they planned to modify their treatment approach for treatment experience patients because of participating in the education.Of note, this assessment also identified topics in which HIV/ID had a high degree of baseline knowledge. Conclusion Participation in this online, interactive, case-based, program significantly improved HIV/ID specialists’ ability to develop individualized care strategies for patients who are treatment experienced. Disclosures All Authors: No reported disclosures