bluuebunny/crossref_metadata_2025_split huggingface dataset:
2500. Fostemsavir Drug–Drug Interaction Profile, an Attachment Inhibitor and Oral Prodrug of Temsavir, for Heavily Treatment Experienced HIV-1-Infected Patients
Authors: Moore Katy P , Mageau A Savannah , Magee Mindy , Gorycki Peter D , Ackerman Peter , Llamoso Cyril 
Published: October 2019

Abstract

Background
Fostemsavir (FTR) is a first-in-class attachment inhibitor being evaluated in heavily treatment-experienced (HTE) HIV-1-infected patients. Active temsavir (TMR) binds to viral envelope glycoprotein 120 and prevents viral attachment and entry into host CD4+ T cells. TMR is primarily metabolized by esterase-mediated hydrolysis with contributions from cytochrome P450 (CYP) 3A4. TMR does not inhibit/induce major CYP or uridine diphosphate glucuronosyltransferase (UGT) enzymes and is a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate. TMR and/or its metabolites inhibit BCRP and organic anion transporter protein 1B1/3 (OATP1B1/3). FTR DDI profile informs coadministration with antiretrovirals (ARV) and other therapeutic classes.

Methods
DDI data from 13 studies were compiled to inform the impact of 17 drugs or drug combinations on TMR and the impact of TMR on 15 drugs such as ARVs, rifamycins, opioid substitutes, statins, oral contraceptives (OC), and H2-antagonsits.

Results
FTR with CYP3A4, P-gp, and/or BCRP inhibitors increase TMR concentrations; but, do not pose clinical concern at therapeutic dose. TMR may be administered with weak/moderate inducers with or without coadministration of CYP3A4, P-gp, and/or BCRP inhibitors such as RTV or COBI. Coadministration with strong inducers is contraindicated. FTR may be coadministered with RBT with or without a PK enhancer. However, co-administration of FTR with RIF is contraindicated. FTR can be given with drugs that increase gastric pH; famotidine did not impact TMR PK. TMR may increase concentrations of drugs that are substrates of OATP1B1/3 and BCRP; therefore, most statins require dose reduction (e.g., rosuvastatin dose is limited to ≤10 mg QD). TMR increased EE exposure 40% with no impact on NE; therefore, FTR may be coadministered with OCs containing ≤30 µg EE. TMR had no clinically meaningful impact on TDF, DRV/RTV, ATV/RTV, ATV, RTV, ETR, MET, or BUP/norBUP PK (Table 1).

Conclusion
FTR can be coadministered with ARVs and most common treatments used to manage HIV co-infections or comorbidities without dose adjustment of either drug except for select HMG-CoA reductase inhibitors and EE-containing OCs. Strong CYP3A inducers are contraindicated.

Disclosures
All authors: No reported disclosures.
2504. Laboratory Evaluation of HIV-1 Viral Load Pooling with Marker-Assisted Deconvolution
Authors: Holland Sabina , DeLong Allison , Liu Tao , Makaretz Anna , Coetzer Mia , Ledingham Lauren , Xu Yizhen , Sam Soya , Sagoe Kwamena , Caliendo Angela , Daniels Michael , Hogan Joseph , Kantor Rami 
Published: October 2019

Abstract

Background
Cost still limits HIV-1 viral load (VL) routine monitoring in resource limited settings (RLS), preventing early detection of virologic failure (VF). Pooled VL testing reduces cost over individual testing (IND). We previously showed in simulation, that additional cost benefits over previously-used pooling deconvolution algorithms can be achieved by using low-cost, routinely-collected clinical markers to determine the order for VL testing in deconvolution (termed marker-assisted minipool plus algorithm; mMPA). This algorithm has not been assessed in-vitro.

Methods
150 samples from 99 Ghanaian adults with HIV on first-line therapy (VF 17%; CD4-VL correlation −0.35) were used to construct 30, 5-sample pools: n = 10 with 0, n = 5 with 1, and n = 15 with 2 individuals with VF. VL testing was with Abbott M2000. Accuracy, number of tests and rounds of testing to deconvolute pools were estimated using four strategies: (1) IND; (2) Minipooling (MP); (3) Minipooling with algorithm (MPA); and (4) mMPA.

Results
Compared with IND, MP and MPA, mMPA reduced total number of tests per pool needed to ascertain VF: MP average 4.3 (95% confidence interval (CI) 3.5–5.2, p> 0.05), MPA 3.0 (95% CI 2.4–3.5, P < 0.001), and mMPA 2.5 (CI 2.0–3.0, P < 0.001). Compared with MP and MPA, mMPA further reduced VL tests by 42% (1.9 tests/pool, CI 1.3–2.4, P < 0.001) and 17% (0.5, CI 0.2–0.8, p = 0.004); and required fewer testing rounds than MPA by 17% (P < 0.01), thus producing results quicker. IND and MP had 100% sensitivity and specificity. MPA and mMPA had similar sensitivity of 96.1% (MPA CI 90.7–100%; mMPA CI 88.0–100.0%) and specificity of 99.5% and 99.2% (98.5–100.0% for MPA and 97.5–100.0% for mMPA). Specifically, 3/150 samples were misclassified with MPA and mMPA: one suppression as VF, and two VF as suppressed.

Conclusion
Laboratory evaluation confirms that deconvolution using mMPA with CD4 or other routinely-collected clinical information as low-cost biomarkers reduces the number of VL assays required to identify VF in a setting with a low prevalence of VF. Implementation of pooled VL testing using mMPA for deconvolution may increase the availability of VL monitoring in RLS. Work is ongoing to reduce complexity and misclassification, required prior to widespread implementation.

Disclosures
All authors: No reported disclosures.
144. Organism Identification and Antibiotic Susceptibilities with Verigene Blood Culture Assay: a Retrospective Single-Center Study
Authors: Tchen Stephanie , Smoke Steven , DeVivo Maria 
Published: October 2019

Abstract

Background
The Verigene blood culture assay is a rapid molecular testing platform for positive blood cultures. Verigene detects a limited number of bacteria and a limited number of antibiotic resistance determinants. While certain Verigene results have clear implications for optimal antibiotic therapy prior to complete antibiotic susceptibility testing, others do not. The purpose of this study was to compare the results of the Verigene blood culture assay with standard organism identification and antibiotic susceptibility testing.

Methods
This was a retrospective cohort study conducted at a single academic medical center. The study period was 14 months from November 2017 to December 2018. All Verigene results from the study period were reviewed and compared with the results of standard organism identification and susceptibility testing. Organism identification and antibiotic susceptibility testing were performed by Vitek MS and Vitek 2. Duplicate results from the same patient were excluded. The primary outcome was the percentage of blood cultures correctly identified by Verigene. Secondary outcomes included the antibiotic susceptibility of organisms identified by Verigene in the presence and absence of resistance determinants and the identity and frequency of organisms not detected by Verigene.

Results
A total of 782 Verigene results were screened. After exclusions, 675 Verigene results including 737 organisms from 597 patients were included. Of 737 organisms, Verigene correctly identified 611 (82.9%), incorrectly identified 19 (2.6%) and was unable to identify 107 (14.5%) off-panel organisms. Tables 1 and 2 outline the antibiotic susceptibility of organisms by the presence or absence of resistance determinants in Gram-negative and Gram-positive bacteria, respectively. Table 3 describes the identities of the organisms not detected by Verigene, stratified by Gram stain result.

Conclusion
The Verigene blood culture assay demonstrated accuracy in identifying organisms and predicting antibiotic susceptibility. These results will help inform the prospective interpretation of Verigene results and subsequent antibiotic selection at the study institution.

Disclosures
All authors: No reported disclosures.
2518. Development And Characterization Of Human Microglial Models To Elucidate HIV Transmission Events And Pathogenesis
Authors: Rai Mohammad Ali , Hammonds Jason E , Spearman Paul , Spearman Paul 
Published: October 2019

Abstract

Background
HIV-associated neurocognitive disorders cause significant morbidity and mortality despite the advent of antiretroviral therapy. An understanding of fundamental mechanisms underlying HIV infection and transmission events in the central nervous system (CNS) is needed. Microglia are resident myeloid cells that are readily infected by HIV and may constitute a CNS reservoir. We evaluated and compared existing microglial cell lines and primary cell-derived microglia as potential model systems for studying HIV-microglia interactions.

Methods
We cultured two immortalized human microglial lines (HMC3, C20) and developed two primary microglial models: induced microglia (iMG) derived from primary human monocytes; and microglial-like cells (iMGL) differentiated from induced pluripotent stem cells (iPSCs). We compared these four microglial cell types to commercially available fetal microglia (PM) for a microglial comparator, and monocyte-derived macrophages as a non-microglial comparator cell. Each cell type was evaluated for the presence of typical myeloid and microglia-specific markers by flow cytometry and immunofluorescence microscopy. HIV infection was performed using macrophage-tropic HIV or VSV-G-pseudotyped HIV.

Results
After differentiation, the iMG and iMGL displayed characteristic microglial morphology: a spindle shape and a reduction in the central body, along with ramified cell processes. Flow cytometry revealed significant differences in surface markers among the cell types. iMG and iMGL displayed CD11b, CD45, CXCR4, CCR5 and lack of expression of CD4 and CX3CR1. In contrast, HMC3, C20, and PM were negative for CD11b, CD45, CX3CR1, CD4, CXCR4. Immunostaining showed that iMG and iMGL were positive for microglial markers TMEM119 and P2RY12. RNA Seq analysis is currently underway to determine gene expression differences between the microglial cell lines and our microglia models. In preliminary results, iMG and iMGL were both readily infected with HIV, and comparison with other lines is ongoing.

Conclusion
There is no standard model available for defining the molecular and cellular events involved in HIV infection of microglia. Significant differences in microgial markers and in HIV receptor and coreceptor levels were noted in this study. iMG and iMGL appear to be viable microglial models susceptible to HIV infection.

Disclosures
All authors: No reported disclosures.
2526. Side Effects of Antiretroviral Therapy in Children with HIV in a Referral Center in Mexico
Authors: Diaz Luis Xochihua , Ortega Javier Ordoñez , Lopez Karen Alejandra Linares , Garcia Itzel Villanueva , Gutierrez Jose Luis Copado 
Published: October 2019

Abstract

Background
Human Inmunodeficiency Virus infection (HIV) is still a challenge in many parts of the world, mainly in children. In Mexico the infection has been decreasing, however we still have cases, in 2018 we had 40 perinatal new cases reported. The antiretroviral therapy has shown to be effective to control the disease but it is not free of adverse effects, the children with vertical transmission are exposed to many years of the antiretroviral therapy.

Methods
Retrospective, observational descriptive study at Instituto Nacional de Pediatría during 2004–2019. We included every children under 18 years old who received treatment for HIV and had a complete medical record.

Results
We found 61 patients under 18 years that fulfill the data for the analysis. 37 (60%) were male, the mean age at diagnosis of HIV infection was 47 months, the antiretroviral therapy that received 57 patients (93.4%) of the study was zidovudine, lamivudine and lopinavir/ritonavir, only 4 received another therapy: 3 of them received abacavir, lamivudine, and lopinavir/ritonavir and the missing one received abacavir, lamivudine and raltegravir. 43% of the children of our study showed adverse effects after the antiretroviral therapy, the mean time of adverse effects presentation was 37 months after the beginning of the treatment. The most common effect was hypertriglyceridemia with 13 cases, in second place we found hypercholesterolemia in 7 cases, and both in 5 cases, other frequent effects were hepatotoxicity in 5 cases, diarrhea in 4 cases, anemia in 3 cases, vomit in 3 cases, abdominal pain and night terrors in 2 cases each one. It was necessary the change of the therapy because of adverse effects in 6 cases (9.8%).

Conclusion
Antiretroviral therapy is effective although it has many side effects. We observe that adverse effects are frequent, almost the half, in pediatric population, it depends on the antiretroviral selection, for children we had only a few options because of the little doses they need or the inability to swallow tablets. It′s important to monitor and control all the adverse effects because they increase morbidity and mortality, especially dyslipidemia, that has been associated with cardiovascular risk and it was the most common effect found in our study.

Disclosures
All authors: No reported disclosures.
2529. Child HIV Exposure and CMV Seroprevalence in Botswana: No Associations with 24-Month Growth and Neurodevelopment
Authors: Moraka Natasha Onalenna , Moyo Sikhulile , Ibrahim Maryanne , Mayondi Gloria , Leidner Jean , Powis Kathleen , Cassidy Adam R , Kammerer Betsy , Smith Christiana , Weinberg Adriana , Musonda Rosemary , Shapiro Roger , Gaseitsiwe Simani , Lockman Shahin 
Published: October 2019

Abstract

Background
HIV-exposed but uninfected (HEU) children are at increased risk for poorer growth outcomes compared with HIV-unexposed/uninfected (HUU) children. Mechanisms underlying the poorer growth and delays in development of HEU children compared HUU children are not fully understood. We sought to define the relationship between child CMV status and HIV− exposure status and determine if a correlation existed between CMV status and growth (and neurodevelopmental) outcomes by 24 months of age in Botswana.

Methods
We used existing data and samples from the observational Botswana Tshipidi study, pregnant women living with HIV (WLHIV) and those without HIV, as well as their infants were enrolled and followed prospectively through 2 years postpartum. We tested 18-month child plasma samples from all available children for anti-HCMV IgG. We evaluated the association between positive (vs. negative) child CMV status at 18 months, and child growth, using the World Health Organization’s Growth Standard adjusted for age and sex and neurodevelopment at 24 months of age, using the Bayley Scales of Child Development (BSID) III.

Results
Of 317 children tested for CMV IgG at 18 months, 215 (67.8%) tested positive. Significantly higher proportions of HUU children had positive CMV serology (82.6%) compared with HEU children (47.4%, P < 0.01); 96.7% of HUU vs. 10.5% of HEU children breastfed. Child CMV infection was not associated with head circumference, weight-for-age, weight-for-height, nor height-for-age z-scores at 24 months. BSID III scores in receptive and expressive language, fine and gross motor, and cognitive domains at 24 months of age also did not differ by child CMV status.

Conclusion
We observed high rates of CMV seropositivity in 18-month-old children in Botswana with significantly higher CMV seropositivity among HUU children likely owing to breastfeeding. Positive CMV serostatus was not associated with child growth or neurodevelopmental outcomes at 24 months.

Disclosures
All authors: No reported disclosures.
2532. Identifying Educational Needs and Improving Provider Knowledge Regarding the Management of Febrile Neutropenia
Authors: Chang Amy , Deresinski Stan , Subramanian Aruna , Medeiros Bruno , PharmD Emily Mui, , Meng Lina , Liedtke Michaela , Holubar Marisa 
Published: October 2019

Abstract

Background
In a retrospective chart review of 211 first episodes of febrile neutropenia (FN) in in-patients with acute myelogenous leukemia evaluating rates of appropriate vs. inappropriate management, we identified frequent noncompliance with national guidelines for the management of FN. We utilized these data to develop an educational intervention targeting front-line providers.

Methods
Based on findings from our chart review, we developed and implemented an interactive, case-based didactic session for advanced practice providers (APPs) and medical students/residents rotating on hematology, targeting inappropriate antibiotic use. Pretest questions were embedded into the lecture, preceding content related to each learning objective. Lecture material included content from national guidelines, literature addressing misconceptions (e.g., vancomycin usage for persistent fever), and data from our institutional antibiogram (Figure 1). A post-test was given directly after the lecture to evaluate knowledge gained.

Results
Five inappropriate behaviors were identified (Figure 2): (1) changing empiric therapy despite clinical stability, (2) misunderstanding piperacillin/tazobactam’s spectrum of activity, (3) inappropriate initiation of antibiotics active against resistant Gram-positive organisms; (4) failure to de-escalate therapy at 72 hours and (5) failure to add Gram-positive coverage when using aztreonam. Lectures were provided to 13 APPs and 17 medical students/residents over 6 sessions. An improvement in knowledge was noted for most learning objectives except for the third, for which misconceptions remained, especially regarding need for vancomycin in the setting of mucositis (Figures 3 and 4). Higher baseline knowledge was noted for medical students/residents than APPs. 93% of learners rated the lecture very/extremely helpful. Learners recommended future content focus on antifungal therapy.

Conclusion
We utilized local practice data to develop educational content for front-line providers. We will convert this lecture into a video-format to be incorporated into hematology rotations to reinforce key concepts. A prospective cohort study to evaluate the impact on prescribing behavior is underway.

Disclosures
All authors: No reported disclosures.
2546. The Mentor Model: Improving Fellow-Level Transitions of Patient Care
Authors: Modi Anita R , Isada Carlos M 
Published: October 2019

Abstract

Background
Our infectious disease fellows rarely see follow-up patients. Yet longitudinal patient care teaches the fellow how to approach chronic illnesses, continued clinical decline, and adverse effects of antimicrobial therapy. Fellows at our institution typically rotate with a different faculty member every 1–2 weeks. Follow-up visits are scheduled with the faculty member. While this model exposes the fellow to a variety of cases and management styles, it limits fellow follow-up opportunities. We developed a model to solve this problem.

Methods
The Mentor Model involves 12-week blocks during which the fellow and a faculty member share the same schedule, facilitating fellow participation in post-discharge visits, re-consultations, and repeat outpatient appointments. We queried our electronic medical record for a list of all consult notes written by fellows during both Mentor Model and traditional (non-Mentor Model) blocks. The number of repeat encounters, or evaluations of an established patient, were tallied and divided by the number of total encounters to determine each fellow’s follow-up rate. This value was compared between Mentor Model and non-Mentor Model blocks.

Results
Historically, our fellows have reported 1–2 follow-ups each over the course of his or her training. Four first-year fellows rotated through two Mentor Model blocks totaling 23 weeks and several non-Mentor Model blocks totaling 14 weeks within the study period. Fellow follow-up rates ranged from 5–12% during non-Mentor Model blocks. One fellow demonstrated increased rates during the first Mentor Model block (5% vs. 9%) and three demonstrated increased rates during the second Mentor Model block (5–11% vs. 9–18%). The most encounters noted for a single patient was five. The majority of repeat encounters occurred in the outpatient setting.

Conclusion
We describe a rotation model designed to improve continuity of patient care among first-year Infectious Disease fellows at our institution. Compared with our previous rotation schedule, the Mentor Model increased fellow follow-ups. Structural changes to promote longitudinal patient care experiences are described in outpatient-heavy training programs. Further interventions to improve fellow follow-up rates in all training programs are merited.

Disclosures
All authors: No reported disclosures.
2560. Assessing Resident Perspectives on Prescribing Pre-Exposure Prophylaxis for HIV
Authors: Shallal Anita , Boapimp Pimpawan , Patel Keshav , Melgar Thomas , Vaillant James 
Published: October 2019

Abstract

Background
Over 15,000 people were living with HIV in Michigan in 2017. Kalamazoo County is one of the ten counties with the highest prevalence rate. Despite the efficacy of pre-exposure prophylaxis (PrEP) and updated guidelines from CDC/USPSTF with daily dosing of oral tenofovir/emtricitabine, 35% of patients encounter a physician who is unwilling to prescribe PrEP. One-third of primary care providers (PCP) are unaware of it. We investigated the perspectives of residents in several primary care-focused residency programs regarding PrEP and barriers to its prescription.

Methods
We surveyed 108 residents at Western Michigan University Homer Stryker M.D. School of Medicine from the departments of Internal Medicine, Medicine-Pediatrics, Pediatrics, Family Medicine, and OB/GYN. An anonymous electronic seven-question survey was sent, accompanied by a brief PrEP guideline.

Results
Of 108 residents surveyed, 53 responded (49%). The majority (45%) were in their intern year (Figure 1). Most respondents (67%) felt somewhat to very comfortable with providing counseling on safe sex practices and HIV prevention (Figure 2). Over 80% of respondents were aware of PrEP prior to reviewing the accompanying guideline. More than 70% of respondents would prescribe PrEP to patients in commercial sex work and serodiscordant couples, but only 30% were willing to prescribe PrEP to heterosexual men or women, and 8% were unwilling to prescribe PrEP at all (Figure 3). The main reason reported for not prescribing PrEP was inadequate knowledge about medication monitoring and follow-up (Figure 4). Only one respondent reported religious or moral beliefs affecting their prescribing habits. The vast majority (98%) of respondents would be more willing to prescribe PrEP with further education.

Conclusion
The majority of residents were comfortable with sex education and counseling on HIV prevention, which could help identify at-risk patients. There was wide variation in willingness to prescribe PrEP among indications, but little variation in reasons why PrEP is not being prescribed. This suggests either limited knowledge about the indications or possibly subconscious bias. Our results are consistent with previous literature that additional medical education on PrEP is essential to its utilization by PCPs.

Disclosures
All authors: No reported disclosures.