GOVERNMENT COMMERCIALIZATION GRANTS AND BUSINESS PERFORMANCE

Australian government offered a number of commercialization grants to businesses from 2009 to 2014. The grants were to support companies and innovators during the commercialization phase of their products and ideas. Focussing on the small firms that are supported by the program, we find that the grant recipient firms tend to invest in capital and research and development (R&D) in larger amounts than a similar comparison group. These firms also experience a faster growth in turnover and a higher probability of exporting, patenting and registering for trademarks. Overall, the program seems to have had a positive impact on firm productivity and innovation activity.

932. Universal Hepatitis C Virus Screening in a Tennessee Tertiary Care Emergency Department

Background Despite hepatitis C virus (HCV) age cohort and risk factor screening recommendations, many at-risk individuals remain undiagnosed. Current screening practices may not adequately capture those at high risk for infection, especially in regions with increasing injection drug use (IDU). Universal HCV screening in a Tennessee tertiary care emergency department (ED) was introduced to help define regional epidemiology and to improve diagnosis and linkage to care. Methods This screening program was implemented in the Vanderbilt University Medical Center ED. Adult patients who underwent phlebotomy for clinical purposes were offered HCV screening. Samples were initially tested for HCV antibodies; if positive, samples were reflexed for HCV RNA testing. Patients with positive HCV RNA tests (i.e., active HCV infection) were notified, counseled, and offered linkage to care. Results A total of 11,637 screening tests were performed between April 1, 2017 and March 31, 2018, with 1,008 (8.7%) HCV antibody positive and 488 (4.2%) RNA positive. Of note, 81 (0.7%) were HCV antibody positive but RNA testing could not be performed due to insufficient sample volume. Several notable populations had high rates of HCV (Table 1). Importantly, 3.9% of people not born between 1945 and 1965 were HCV RNA positive, and they were the majority (63.5%) of patients with active HCV (Table 2). A minority (31.6%) of those with active HCV had a known history of IDU (Table 2). Conclusion HCV is common among patients presenting for emergency care at a Tennessee tertiary care ED. Universal screening identified many infections that would have been missed using age cohort and risk factors alone. ED HCV screening may be a useful method to augment guideline-based testing and intervene among populations not consistently screened. Disclosures C. A. Chastain, Gilead Sciences, Inc.: Grant Investigator and Research Contractor, Grant recipient and Research support. J. Johnson, Gilead Sciences, Inc.: Grant Investigator, Grant recipient. K. Miller, Gilead Sciences, Inc.: Grant Investigator, Grant recipient. J. H. Han, Gilead Sciences, Inc.: Grant Investigator, Grant recipient. W. H. Self, Gilead Sciences, Inc.: Grant Investigator, Grant recipient.

937. Virally Suppressed PLH Switching From Abacavir to Tenofovir Alafenamide Did Not Have Changes in Immune Activation or Inflammation

Background Abacavir (ABC) use has been associated with increased risk of myocardial infarction in persons living with HIV (PLH). Its mechanism is unknown, but may involve immune activation inflammation, and/or altered platelet reactivity. In the current analysis, we compared changes in biomarkers of immune activation and inflammation associated with increased cardiovascular (CV) mortality in virally suppressed PLH who switched off ABC to tenofovir alafenamide (TAF) to those who remained on ABC. Methods In a randomized, double-blinded, active-controlled trial (GS US 311–1717), virally suppressed PLH on a stable regimen containing ABC plus lamivudine (3TC) were randomly assigned (1:1) to maintain therapy or to switch to TAF plus emtricitabine (FTC) while continuing their third agent. At baseline (BL) and weeks 4, 12, 24, and 48 plasma markers (IL-6, hsCRP, D-Dimer, sCD14, sCD163, TNF-R1, and TNF-R2) were measured by ELISA; Lp-PLA2 levels were measured by the Plac assay. Differences between treatment groups overtime were assessed by 2-sided Wilcoxon rank-sum tests. Results Of 556 PLH randomized, 548 had samples available for biomarker assessments (TAF: 274; ABC: 274), both arms were of similar CD4 (median 671 cells/μL), age (median 52 years), race (73% white), but there were fewer women in the TAF arm (14% vs. 22%, P = 0.015) at baseline (BL). Mean BL ASCVD scores were 7.9 in both arms (>7.5 is increased CV risk). BL biomarker concentrations were similar between arms: most had high concentrations of Lp-PLA2 ≥200 ng/mL (94%) and one-third had elevated hsCRP levels >3 mg/L (34%). After switching from ABC to TAF, sCD14 had an early (W12) decreased (−3.4% vs. −0.1%, P = 0.023), while sCD163 increased at both W4 (2.5% vs. −1.2%, P = 0.02) and W24 (1.4% vs. −0.8%, P = 0.025) in the TAF arm; levels of sTNF-R1 also increased through W24 (3.2% vs. 0.2%, P = 0.003) (figure). There were no significant differences in percentage changes from BL between arms for levels of Lp-PLA2, hsCRP, IL-6, D-dimer, or TNF-R2. Conclusion Prior to switching from ABC to TAF, virally suppressed PLH with mean ASCVD scores of 7.9 had elevated levels of CV risk markers (Lp-PLA2 and hsCRP). Switching off ABC to TAF was not associated with any meaningful change in markers of immune activation or inflammation, suggesting that the ABC-associated increased MI risk may involve an alternative etiology. Disclosures G. Mccomsey, Merck: Consultant, Consulting fee. ViiV: Consultant, Consulting fee. Gilead: Consultant, Consulting fee. Astellas: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. P. Mallon, Gilead Sciences: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Grant recipient and Speaker honorarium. GSK Ireland: Grant Investigator and Scientific Advisor, Grant recipient. A. Winston, Gilead, ViiV Healthcare, BMS, Janssen and Merck: Consultant, Grant Investigator, Investigator and Speaker’s Bureau, Educational grant, Grant recipient, Research grant and Speaker honorarium. D. Sengupta, Gilead Sciences: Employee and Shareholder, Salary and Stock. M. Yan, Gilead Sciences: Employee and Shareholder, Salary and Stock. M. S. Rhee, Gilead Sciences: Employee and Shareholder, Salary and Stock. M. Das, Gilead Sciences: Employee and Shareholder, Salary and Stock.

LB1. Doravirine/Lamivudine/Tenofovir DF Continues to Be NonInferior to Efavirenz/Emtricitabine/Tenofovir DF in Treatment-Naïve Adults With HIV-1 Infection: Week 96 Results of the DRIVE-AHEAD Trial

Background Doravirine (DOR) is a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI). In the phase 3 DRIVE-AHEAD trial in HIV-1-infected treatment-naïve adults, DOR demonstrated noninferior efficacy to efavirenz (EFV) and favorable profiles for neuropsychiatric tolerability and lipids at 48 weeks. We present data through week 96. Methods DRIVE- AHEAD (Clinical Trials Registration: NCT02403674) is a phase 3, multicenter, double-blind, noninferiority trial that compared DOR with EFV. Eligible participants were HIV-1-infected treatment-naïve adults with pre-treatment HIV-1 RNA ≥1,000 copies/mL. Participants were randomized (1:1) to a fixed-dose regimen of DOR 100 mg, lamivudine 300 mg and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF) QD or EFV 600 mg, emtricitabine 200 mg and TDF 300 mg (EFV/FTC/TDF) QD for up to 96 weeks. Randomization was stratified by screening HIV-1 RNA (≤/>100,000 copies/mL) and hepatitis B/C co-infection (yes/no). The efficacy endpoint of interest at week 96 was HIV-1 RNA <50 copies/mL with predefined noninferiority margin of 10%. Safety endpoints of interest included occurrence of pre-specified neuropsychiatric adverse events and mean change from baseline in fasting lipid levels at week 96. Results Of 734 participants randomized, 728 received study drug and were included in analyses (mean age 33 years, 85% male, 48% white, 19% black, 34% Hispanic). At week 96, HIV-1 RNA <50 copies/mL was achieved by 77.5% of DOR/3TC/TDF recipients vs. 73.6% of EFV/FTC/TDF recipients (difference 3.8%, 95%CI [−2.4, 10.0]). No additional phenotypic resistance to DOR was observed between weeks 48 and 96, while two additional participants in the EFV/FTC/TDF group developed resistance to EFV. Dizziness, sleep disorders/disturbances, altered sensorium, and rash were less frequent in DOR/3TC/TDF recipients than in EFV/FTC/TDF recipients. Fasting LDL-C and non-HDL-C increased in the EFV/FTC/TDF group but not in the DOR/3TC/TDF group, while change in total cholesterol/HDL-C ratio was similar. Conclusion Week 96 results support non-inferiority of DOR/3TC/TFD to EFV/FTC/TDF established at Week 48 with no additional DOR resistance between week 48 and 96. DOR/3TC/TDF was safe and well-tolerated with fewer neuropsychiatric and rash events and favorable lipid profile compared with EFV/FTC/TDF. Disclosures C. Orkin, AbbVie, Abbott, Boehringer Ingelheim, BMS, Gilead, GSK, Janssen, ViiV: Grant Investigator and Research Contractor, Research grant and Research support. K. Squires, Merck & Co., Inc.: Ad Board, Ad Board. Gilead Sciences: Grant, Ad Board. VIIV: Ad Board, Ad Board. Bristol Myers Squibb: Ad Board, Ad Board. Janssen: Ad Board, Ad Board. J. M. Molina, Gilead: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee. ViiV: Scientific Advisor, Consulting fee. Teva: Scientific Advisor, Consulting fee. P. Sax, Gilead: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research grant. ViiV Healthcare: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research grant. Merck: Consultant and Grant Investigator, Consulting fee, Grant recipient and Research grant. Janssen: Consultant, Consulting fee. BMS: Grant Investigator, Grant recipient and Research grant. W. Wong, Merck & Co., Inc.: Research Contractor, Research grant. G. Lin, Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc.: Employee and Shareholder, May hold stock/stock options in the company and Salary. S. Kumar, Merck & Co., Inc.: Employee and Shareholder, Salary. G. Hanna, Merck & Co., Inc.: Employee and Shareholder, Salary. C. Hwang, Merck & Co., Inc.: Employee and Shareholder, Salary. E. Martin, Merck & Co., Inc.: Employee and Shareholder, Salary. H. Teppler, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA: Employee, May hold stock/stock options in the company and Salary.

872. PROPHETIC: Predicting Pneumonia in Hospitalized Patients in the ICU—A Model and Scoring System

Background Prospectively identifying patients at highest risk for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) by implementing a risk assessment scoring tool may help focus prevention efforts, optimize the screening process to improve clinical trial feasibility, and enhance development of new antibacterial agents. Methods Within the intensive care units (ICU) of 28 US hospitals, between February 6, 2016 and October 7, 2016, patients hospitalized >48 hours and receiving high levels of respiratory support were prospectively followed for meeting the definition of HABP/VABP recommended in US FDA draft guidance. Patient demographics, medical comorbidities, and treatment exposures were recorded. The association between candidate risk factors and odds of developing HABP/VABP was evaluated with a multivariable logistic regression model. Risk factors were selected using backward selection with α = 0.1 for model inclusion. A web-based scoring system was developed to estimate the risk of HABP/VABP from the risk factors identified. Results A total of 5,101 patients were enrolled, of whom 1,005 (20%) developed HABP/VABp. 4,613 patients were included in the model, excluding 488 (10%) with HABP/VABP at or before enrollment. There are 15 variables included in the model. APACHE II admission score >20 (P < 0.001, OR 2.14, 95% CI 2.00–2.29), admission diagnosis of trauma (P < 0.001, OR 3.31, 95% CI 1.90–5.74), frequent oral or lower respiratory tract suctioning (P < 0.001, OR 2.33, 95% CI 1.81–2.99), and receipt of enteral nutrition (P < 0.001, OR 2.31, 95% CI 1.69–3.16) were the key drivers of increased pneumonia risk. The model demonstrated excellent discrimination (bias-corrected C-statistic 0.861, 95% CI 0.843–0.880). The web-based scoring system can be accessed via this link: https://ctti-habpvabp.shinyapps.io/web_based_tool/. Conclusion Using a web-based scoring system, ICU patients at highest risk for developing HABP/VABP can be accurately identified. Prospective implementation of this tool may assist in focusing additional prevention efforts on the highest risk patients and enhance new drug development for HABP/VABP. Disclosures S. P. Bergin, CTTI: Investigator and Scientific Advisor, Research support and Travel to study related meetings. A. Coles, CTTI: Investigator and Scientific Advisor, Salary. S. B. Calvert, CTTI: Employee, Salary. M. J. Zervos, CTTI: Investigator, Research support. A. C. Bardossy, CTTI: Investigator, Research support. M. Kollef, CTTI: Investigator, Research support. M. J. Durkin, CTTI: Investigator, Research support. M. Sims, CTTI: Investigator, Research support. C. Greenshields, CTTI: Investigator, Research support. B. A. Kabchi, CTTI: Investigator, Research support. H. K. Donnelly, CTTI: Collaborator and Scientific Advisor, Research support and Salary. P. Tenaerts, CTTI: Employee, Salary. P. Gu, CTTI: Collaborator, Research support and Salary. V. G. Fowler Jr., CTTI: Investigator and Scientific Advisor, Research support and Salary. Merck: Consultant, Grant Investigator and Scientific Advisor, Consulting fee, Grant recipient and Research support. Cerexa/Actavis/Allegan: Grant Investigator, Grant recipient. Pfizer: Consultant and Grant Investigator, Consulting fee and Grant recipient. Advanced Liquid Logics: Grant Investigator, Grant recipient. NIH: Investigator, Grant recipient, Research support and Salary. MedImmune: Consultant and Grant Investigator, Consulting fee and Grant recipient. Basilea: Consultant and Grant Investigator, Consulting fee and Grant recipient. Karius: Grant Investigator, Grant recipient. Contrafect: Consultant and Grant Investigator, Consulting fee and Grant recipient. Regeneron: Grant Investigator, Grant recipient. Genentech: Consultant and Grant Investigator, Consulting fee and Grant recipient. Achaogen: Consultant, Consulting fee. Astellas: Consultant, Consulting fee. Arsanis: Consultant, Consulting fee. Affinergy: Consultant, Consulting fee. Bayer: Consultant, Consulting fee. Cerexa: Consultant, Consulting fee. Cubist: Consultant, Consulting fee. Debiopharm: Consultant, Consulting fee. Durata: Consultant, Consulting fee. Grifols: Consultant, Consulting fee. Medicines Co.: Consultant, Consulting fee. Novartis: Consultant, Consulting fee. Novadigm: Consultant, Consulting fee. Theravance: Consultant, Consulting fee and Speaker honorarium. xBiotech: Consultant, Consulting fee. Green Cross: Consultant, Speaker honorarium. T. L. Holland, CTTI: Investigator and Scientific Advisor, Research support and Salary.

1768. Efficacy and Safety of Switching From Boosted-Protease Inhibitors (bPI) Plus Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) Regimens to the Once Daily (QD), Single-Tablet Regimen (STR) of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Virologically Suppressed, HIV-1-Infected Adults: Week 96 Results of the Phase 3, Randomized, Non-Inferiority EMERALD Trial

Background The QD STR D/C/F/TAF 800/150/200/10 mg was noninferior to bPI + F/TDF at 48 weeks in EMERALD. Efficacy and safety of D/C/F/TAF through week 96 are presented. Methods EMERALD (NCT02269917) is a randomized, active-controlled, open-label, international, multicenter noninferiority trial. Virologically suppressed (VL<50 c/mL for ≥2 months) ART experienced (previous non-DRV VF allowed) HIV-1-infected adults were randomized (2:1) to switch to D/C/F/TAF or continue bPI + F/TDF over 48 weeks. Patients could then continue on D/C/F/TAF or switch from bPI + F/TDF to D/C/F/TAF at week 52 (Late switch, 44 weeks D/C/F/TAF exposure) in a single-arm extension phase until week 96. The percentage of patients with virologic rebound (confirmed VL ≥50 c/mL) cumulative through week 48 and week 96 were primary and secondary endpoints, respectively. Results Of 1141 randomized and treated patients (58% had received ≥5 previous ARVs including screening ARVs; 15% had previous non-DRV VF), 1,080 continued in the extension phase (N = 728 D/C/F/TAF; N = 352 late switch). Few patients had virologic rebound cumulative through week 96 in the D/C/F/TAF arm (3.1%, 24/763). Virologic rebound occurred in 2.3% (8/352) in the late switch arm over 44 weeks D/C/F/TAF treatment. Many rebounders (14/24 and 2/8) resuppressed by week 96. At week 96 a high percentage of patients in the D/C/F/TAF arm (90.7%, 692/763) were suppressed (VL<50 c/mL). In the late switch arm, 93.8% (330/352) maintained virologic suppression after 44 weeks of treatment. No DRV, primary PI, TFV, or FTC RAMs were seen post baseline. Few serious AEs and AE related discontinuations occurred in either arm (Table 1). Improvements in renal and bone parameters were maintained in the D/C/F/TAF arm and seen in the late switch arm (week 52–96), with a small change in TC/HDL-C ratio (Table 1). Conclusion Switching to D/C/F/TAF maintained high virologic suppression rates (>90%) at week 96 with no resistance development, and was well tolerated over 96 weeks with bone, renal, and lipid safety consistent with known TAF and cobicistat profiles. Efficacy and safety results in the late switch arm were consistent with week 48 results in the D/C/F/TAF arm. D/C/F/TAF combines the efficacy and high genetic barrier to resistance of DRV with the safety benefits of TAF, even in patients with a history of non-DRV VF. Disclosures J. Eron Jr., Gilead: Consultant and Grant Investigator, Consulting fee and Research grant. Janssen: Consultant, Consulting fee and Research grant. C. Orkin, AbbVie, Abbott, Boehringer Ingelheim, BMS, Gilead, GSK, Janssen, ViiV: Grant Investigator and Research Contractor, Research grant and Research support. D. Cunningham, Janssen: Investigator, Research grant. Gilead: Investigator, Research grant. F. Pulido, Janssen: Consultant, Investigator and Scientific Advisor, Consulting fee, Research support and Speaker honorarium. F. Post, Gilead: Consultant and Grant Investigator, Consulting fee and Grant recipient. Viiv: Grant Investigator, Grant recipient. Janssen: Consultant, Consulting fee. MSD: Consultant, Consulting fee. S. De Wit, Janssen: Investigator, Research grant. E. Lathouwers, Janssen: Employee and Shareholder, Salary. V. Hufkens, Janssen: Employee and Shareholder, Salary. R. Petrovic, Janssen R&D: Independent Contractor, Consulting fee. E. Van Landuyt, Janssen: Employee and Shareholder, Salary.