525. Atovaquone for Treatment of COVID-19 (Ataq COVID-19) Trial

Abstract Background Our group performed an in-silico screen to identify FDA approved drugs that inhibit SARS-C0V-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods Enrolled patients were randomized in a 2:1 fashion to atovaquone 1500 mg twice daily versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Patients agreed to allow collection of saliva at baseline and twice a day while hospitalized or up to 10 days. Saliva was collected and RNA extracted for viral load (VL) measurement by Real-time PCR. Our primary outcome was to examine the between group differences in log transformed VL(copies/mL) using generalized linear mixed-effect models of repeated measures from all samples. Additional analysis of Atovquone plasma concentrations were examined and correlated with viral load and body mass index (BMI). Results Of the 61 patients enrolled; 41 were received atovaquone and 19 placebo. Overall the population was predominately male Hispanic with a mean age of 51 years. The two groups were balanced (Table 1) with regard to age, gender, race, co-morbidities, days from onset of symptoms, baseline oxygen requirements, and receipt of COVID-19 specific standard of care treatment. A higher proportion with diabetes was noted in the Atovaquone arm. The log10 VL was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Although there was a decrease in VL over time, there was no differences between the atovaquone plus standard of care arm versus the standard of care arm (Figure 1). Additional analysis of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, inverse association between atovaquone levels and BMI (rho -0.44, p=0.03), and Day 5 concentrations and VL (rho -0.54, p=0.005). Figure 1. Mean viral load of COVID-19 over time of atovaquone (blue) vs. placebo (red). Table 1. Baseline characteristics Conclusion Although atovaquone showed promising in vitro antiviral properties for COVID-19, in this pilot study we did not detect a change in VL in patients who received atovaquone compared to placebo, possibly due to failure of patients achieve adequate drug levels. Disclosures Mamta K. Jain, MD, MPH, Gilead Sciences Inc. (Individual(s) Involved: Self): Research Grant or Support, Scientific Research Study Investigator; GlaxoSmithKline (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): Scientific Research Study Investigator; Vasgene (Individual(s) Involved: Self): Scientific Research Study Investigator

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912. Expansion of Hepatitis C Treatment with New Medicaid Subscription Model in Louisiana

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1107 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S547-S548

Author(s):

Lauren E Richey ◽

Yussef Bennani ◽

Maria Frontini

Keyword(s):

Viral Load ◽

Hepatitis C ◽

Research Study ◽

Laboratory Data ◽

Scientific Research ◽

Undetectable Viral Load ◽

Fibrosis Score ◽

Medicaid Program ◽

Hepatitis C Treatment ◽

Study Investigator

Abstract Background It is estimated that nearly 80,000 people with hepatitis C are living in Louisiana, many with Medicaid coverage. Previously, only Medicaid patients free from drugs and alcohol with a fibrosis score of F3 or F4 were eligible for treatment, resulting in few patients receiving treatment. Beginning in July 2019, generic sofosbuvir/velpatasvir was made available through the Medicaid program in a subscription model, allowing unlimited hepatitis C treatment in Louisiana’s Medicaid program for 5 years at a set price to the program. This has dramatically expanded access to Hepatitis C treatment for people with Medicaid in Louisiana. Methods Patients with Hepatitis C seen in the Infectious Diseases Center at University Medical Center in New Orleans, in 2020 by the 5 main hepatitis C providers were included. Demographics and laboratory data were collected to determine outcomes. Results Most patients with a hepatitis C (HCV) viral load and insurance data had Medicaid (80%, N=275). Twenty-two (8%) were HIV co-infected. Most were men (75%) and African-American (77%). Among the mono-infected patients with Medicaid and an HCV viral load, 216 (85%) had an undetectable viral load by the beginning of June 2021. Of the remaining 37 patients, 30 patients were prescribed treatment; but did not take it (n=4), didn’t follow-up (n=23), or followed-up but never got labs (n=3). One was treated but had a treatment failure (n=1). Six of the 37 were not prescribed medications due to a short life expectancy or significant drug interactions. The percentage of patients with an undetectable viral load was similar by gender and race, however younger age groups had lower viral suppression. In those aged less than 35, only 47% had an undetectable viral load and among those aged 36 to 44, it was 66%. Using the previous criteria of requiring a fibrosis score of F3 or F4, only 20% (n=44) would have been eligible for medicine to treat hepatitis C. Conclusion The new hepatitis C treatment subscription model with resultant removal of previous barriers has dramatically expanded treatment for people with Medicaid in Louisiana. More than five times the number of Medicaid patients received treatment in 2020 in our academic medical clinic. Disclosures Yussef Bennani, MD, MPH, Gilead Sciences (Scientific Research Study Investigator)ViiV Healthcare (Scientific Research Study Investigator)

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1103. Minocycline (MIN) Pharmacodynamics (PD) against Stenotrophomonas maltophilia (STM) in a Neutropenic Murine Thigh Infection Model

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1297 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S643-S643

Author(s):

Andrew J Fratoni ◽

David P Nicolau ◽

Joseph L Kuti

Keyword(s):

Research Study ◽

Treatment Options ◽

Scientific Research ◽

Compartment Model ◽

Infection Model ◽

Log10 Reduction ◽

Study Investigator ◽

Research Grant

Abstract Background Antibiotic treatment options for serious STM infections are limited. MIN displays in vitro activity against STM; however, limited data supports optimal dosing for STM. Herein, we employed the murine neutropenic thigh infection model to assess MIN PD against STM. Methods Four clinical STM isolates with MIN MICs 0.25 – 1 mg/L were included. Both thighs of neutropenic ICR mice were inoculated with bacterial suspensions of 107 colony forming units (CFU)/mL. Mice received uranyl nitrate on Day -3 to provide predictable renal impairment. Two hours after inoculation, MIN or control was administered subcutaneously. Pharmacokinetic (PK) studies of 2.5, 25, 50, and 100 mg/kg were conducted. Previously reported protein binding of 78.1% was used to define free exposure. Dose ranging studies were conducted on all STM to assess in vivo activity over a range of MIN exposures. MIN total daily doses (TDD) of 10, 20, and 50 mg/kg were fractionated q24h, q12h, and q6h against a single STM to determine the PD index best correlated with reductions in CFU/mL. Efficacy was measured in log10CFU/thigh at 24h compared with 0h controls. Composite CFU data were fitted to an Emax model to determine the fAUC/MIC exposure for stasis and 1 log10 reduction. Results MIN PK was linear up to 50 mg/kg and well described by a 1 compartment model with first order absorption and elimination. Mean PK parameters across the linear range were: Vd, 2.97 L/kg; K01, 10.62 1/h; and K10, 0.35 1/h. Mean ± SD bacterial burden at 0h across all isolates was 6.17±0.20 log10CFU/thigh. In 24h controls, bacterial growth was 7.90±0.85 log10CFU/thigh. A dose response was observed across all isolates using TDD of 2-300 mg/kg. PD indices correlated with CFU reductions as follows: fAUC/MIC (R2=0.613), fCmax/MIC (R2=0.590), and %fT >MIC (R2=0.504). The fAUC/MIC needed for stasis and 1 log10 reduction at 24h was 9.6 and 23.6, respectively. Conclusion These are the first data describing MIN PD against STM. Against these STM, MIN fAUC/MIC was the PD index best correlated with CFU reductions. The exposure thresholds defined in this study will be useful in designing optimal MIN dosing regimens for treating STM infections and re-assessment of the current susceptibility breakpoint. The study was funded under FDA Contract 75F40120C00171. Disclosures David P. Nicolau, PharmD, Abbvie, Cepheid, Merck, Paratek, Pfizer, Wockhardt, Shionogi, Tetraphase (Other Financial or Material Support, I have been a consultant, speakers bureau member, or have received research funding from the above listed companies.) Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)BioMérieux (Consultant, Research Grant or Support, Speaker’s Bureau)Contrafect (Scientific Research Study Investigator)GSK (Consultant)Merck (Research Grant or Support)Paratek (Speaker’s Bureau)Roche Diagnostics (Research Grant or Support)Shionogi (Research Grant or Support)Summit (Scientific Research Study Investigator)

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543. Molnupiravir Maintains Antiviral Activity Against SARS-CoV-2 Variants In Vitro and in Early Clinical Studies

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.742 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S373-S373

Author(s):

Jay Grobler ◽

Julie Strizki ◽

Nicholas Murgolo ◽

Wei Gao ◽

Youfang Cao ◽

...

Keyword(s):

Clinical Trials ◽

Antiviral Activity ◽

Viral Genome ◽

Research Study ◽

Scientific Research ◽

Spike Protein ◽

Research Support ◽

Study Investigator ◽

Research Grant

Abstract Background Molnupiravir (MOV, MK-4482, EIDD-2801) is an orally administered prodrug of N-hydroxycytidine (NHC, EIDD-1931), a nucleoside with broad antiviral activity against a range of RNA viruses. MOV acts by driving viral error catastrophe following its incorporation by the viral RdRp into the viral genome. Given its mechanism of action, MOV activity should not be affected by substitutions in the spike protein present in SARS-CoV-2 variants of concern which impact efficacy of therapeutic neutralizing antibodies and vaccine induced immunity. We characterized MOV activity against variants by assessing antiviral activity in vitro and virologic response from the Phase 2/3 clinical trials (MOVe-In, MOVe-Out) for treatment of COVID-19. Methods MOV activity against several SARS-CoV-2 variants, was evaluated in an in vitro infection assay. Antiviral potency of NHC (IC50) was determined in Vero E6 cells infected with virus at MOI ~0.1 by monitoring CPE. Longitudinal SARS-CoV-2 RNA viral load measures in participants enrolled in MOVe-In and MOVe-Out were analyzed based on SARS-CoV-2 genotype. Sequences of SARS-CoV-2 from study participants were amplified from nasal swabs by PCR and NGS was performed on samples with viral genome RNA of >22,000 copies/ml amplified by primers covering full length genome with Ion Torrent sequencing to identify clades represented in trial participants. SARS-CoV-2 clades were assigned using clade.nextstrain.org. Results In vitro, NHC was equally effective against SARS-CoV-2 variants B.1.1.7 (20I), B.1351 (20H), and P1 (20J), compared with the original WA1 (19B) isolate. In clinical trials, no discernable difference was observed in magnitude of viral response measured by change from baseline in RNA titer over time across all clades represented including 20A through 20E and 20G to 20I. No participants at the time of the study presented with 20F, 20J, or 21A. Conclusion Distribution of clades in participants in MOVe-In and MOVe-Out was representative of those circulating globally at the time of collection (Oct 2020 – Jan 2021). Both in vitro and clinical data suggest that spike protein substitutions do not impact antiviral activity of MOV and suggest its potential use for the treatment of SARS-CoV-2 variants. Disclosures Jay Grobler, PhD, Merck & Co., Inc. (Employee, Shareholder) Julie Strizki, PhD, Merck & Co., Inc. (Employee, Shareholder) Nicholas Murgolo, PhD, Merck & Co., Inc. (Employee, Shareholder) Wei Gao, PhD, Merck & Co., Inc. (Employee, Shareholder) Youfang Cao, PhD, Merck & Co. (Employee) Ying Zhang, PhD, Merck & Co., Inc. (Employee, Shareholder) Jiejun Du, PhD, Merck & Co., Inc. (Employee, Shareholder) Manoj Nair, PhD, Merck & Co., Inc. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Yaoxing Huang, PhD, Merck & Co., Inc. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Yang Luo, PhD, Merck & Co., Inc. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Daria Hazuda, PhD, Merck & Co., Inc. (Employee, Shareholder) David D. Ho, MD, Merck & Co., Inc. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) David D. Ho, MD, Brii Biosciences (Individual(s) Involved: Self): Consultant; Merck (Individual(s) Involved: Self): Research Grant or Support; RenBio (Individual(s) Involved: Self): Consultant, Founder, Other Financial or Material Support, Shareholder; WuXi Biologics (Individual(s) Involved: Self): Consultant

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LB3. Baricitinib plus Standard of Care for Hospitalized Adults with COVID-19 on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation: Results of a Randomized, Placebo-Controlled Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1644 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S808-S809

Author(s):

E Wesley Ely ◽

Athimalaipet V Ramanan ◽

Cynthia E Kartman ◽

Stephanie de Bono ◽

Ran Liao ◽

...

Keyword(s):

Mechanical Ventilation ◽

Extracorporeal Membrane Oxygenation ◽

Research Study ◽

Controlled Trial ◽

Invasive Mechanical Ventilation ◽

Scientific Research ◽

Standard Of Care ◽

Research Support ◽

Study Investigator ◽

All Cause Mortality

Abstract Background Interventions to reduce mortality in critically ill patients with COVID-19 are a crucial unmet medical need. Baricitinib (BARI) is an oral, selective Janus kinase (JAK)1/JAK2 inhibitor with efficacy in hospitalized adults with COVID-19. Treatment with BARI 4-mg was evaluated in critically ill adult patients with COVID-19 with baseline need for invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO). Methods COV-BARRIER (NCT04421027) was a randomized double-blind, placebo-controlled trial in patients with confirmed SARS-CoV-2 infection and elevation of ≥ 1 serum inflammatory marker. In this newly completed substudy, enrolled participants (not previously reported) from 4 countries on IMV or ECMO at study entry were randomly assigned 1:1 to once-daily BARI 4-mg or placebo (PBO) for up to 14 days plus standard of care (SOC), which included baseline systemic corticosteroid use in 86% of patients. The prespecified exploratory endpoints included all-cause mortality and number of ventilator-free days (VFDs) through Day 28. Results Characteristics for 101 participants are shown in Table 1. Treatment with BARI significantly reduced all-cause mortality by Day 28 compared to PBO [39.2% vs 58.0%, respectively; hazard ratio (HR) = 0.54 (95%CI 0.31, 0.96), p=0.030, relative risk (RR) = 0.68 (95%CI 0.45, 1.02); Figure 1A]. One additional death was prevented for every six BARI-treated patients. Significant reduction in mortality was also observed by Day 60 [45.1% vs 62.0%; HR = 0.56 (95%CI 0.33, 0.97), p=0.027, RR = 0.73 (95%CI 0.50, 1.06); Figure 1B]. Patients treated with BARI showed a numerical reduction in the duration of IMV and duration of hospitalization vs PBO and more BARI treated patients recovered (Table 2). No new safety findings were observed (Table 2). Conclusion Treatment with BARI+SOC (corticosteroids) resulted in an absolute risk reduction in mortality of 19% at Day 28 and 17% at Day 60 in patients with COVID-19 who were on IMV or ECMO at enrollment. These results are consistent with the reduction in mortality observed in the less severely ill hospitalized patients in the primary COV-BARRIER study population. Disclosures E. Wesley Ely, MD, CDC (Grant/Research Support)Eli Lilly (Other Financial or Material Support, Unpaid consultant)NIH (Grant/Research Support)VA (Grant/Research Support) Athimalaipet V. Ramanan, FRCP, AbbVie (Consultant, Speaker’s Bureau)Eli Lilly and Company (Consultant, Grant/Research Support, Speaker’s Bureau)Novartis (Consultant, Speaker’s Bureau)Pfizer (Consultant, Speaker’s Bureau)Roche (Consultant, Speaker’s Bureau)Sobi (Consultant, Speaker’s Bureau)UCB (Consultant, Speaker’s Bureau) Cynthia E. Kartman, RN BSN, Eli Lilly and Company (Employee, Shareholder) Stephanie de Bono, MD PhD, Eli Lilly and Company (Employee, Shareholder) Ran Liao, PhD, Eli Lilly and Company (Employee, Shareholder) Maria Lucia B Piruzeli, MD, Eli Lilly and Company (Employee, Shareholder) Sujatro Chakladar, PhD, Eli Lilly and Company (Employee, Shareholder) Vincent Marconi, MD, Bayer (Consultant, Scientific Research Study Investigator)Eli Lilly (Consultant, Scientific Research Study Investigator)Gilead Sciences (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator)

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983. Outcomes of Candida Bone and Joint Infections in Eight Patients from a Phase 3 Open-label Study (FURI)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1177 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S583-S583

Author(s):

John W Sanders ◽

Caryn Morse ◽

Oliver Cornely ◽

Philipp Koehler ◽

Robert Krause ◽

...

Keyword(s):

Research Study ◽

Joint Infection ◽

Scientific Research ◽

Panel Member ◽

Standard Of Care ◽

Research Support ◽

Open Label ◽

Review Panel ◽

Joint Infections ◽

Study Investigator

Abstract Background Candida osteoarticular infections are often preceded by candidemia with the intervertebral discs and knee joints the most common area for candidemic seeding. Candida osteomyelitis has significant morbidity and diagnosis is often delayed difficult to treat. Treatment courses are usually long and there are limited oral options available for patients who have an azole-resistant infection. Oral ibrexafungerp is an investigational broad-spectrum glucan synthase inhibitor antifungal with activity against Candida and Aspergillus species, including azole- and echinocandin-resistant strains. A Phase 3 open-label, single-arm study of ibrexafungerp (FURI; NCT03059992) is ongoing for the treatment of patients with fungal disease refractory or who intolerant of to standard of care antifungal therapy. Table 1. FURI Bone and Joint Infection Outcomes Methods FURI subjects were eligible for enrollment if they have proven or probable, severe mucocutaneous candidiasis, invasive candidiasis or invasive aspergillosis and documented evidence of failure to, intolerance to, or toxicity related to a currently approved standard-of-care antifungal treatment or can not receive approved oral antifungal options (e.g., susceptibility of the organism) or a continued IV antifungal therapy is clinically undesirable or unfeasible. Results An independent Data Review Committee (DRC) provided an assessment of treatment response for a total 74 subjects enrolled in the FURI study from 22 centers in US, UK and EU treated with ibrexafungerp for mucocutaneous or invasive fungal infections from 2016- 2020. There were 8 subjects out of the 74 subjects who were diagnosed with various bone and joint infections, 5 subjects with spondylodiscitis, 1 subject with a knee/prosthetic joint infection and 2 subjects with bone infections, one of the tibia and one of the zygomatic arch. Table 1 shows outcomes for this patient group, five (75%) patients had a clinical benefit (complete or partial response and stable response), one (12.5%) had progression of disease and one patient was indeterminate. The median days of therapy for this group was 210.5 days. Conclusion Analysis of 8 subjects from the FURI study indicates that oral ibrexafungerp provides a promising therapeutic response in option for patients with bone and/or joint infections. Disclosures Caryn Morse, MD, Chimerix (Scientific Research Study Investigator)Covis Pharma (Scientific Research Study Investigator)Gilead Sciences Inc. (Scientific Research Study Investigator)Ridgeback Biotherapeutics (Scientific Research Study Investigator)Roche (Scientific Research Study Investigator)SCYNEXIS, Inc. (Scientific Research Study Investigator)Theratechnologies (Advisor or Review Panel member)Viiv (Advisor or Review Panel member) Oliver Cornely, Prof., Actelion (Consultant, Grant/Research Support)Al-Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Consultant)Amplyx (Consultant, Grant/Research Support)Astellas (Consultant, Grant/Research Support)Basilea (Consultant, Grant/Research Support)Biocon (Consultant)Biosys (Consultant)Cidara (Consultant, Grant/Research Support)CoRe Consulting (Consultant)Da Volterra (Consultant, Grant/Research Support)DFG (German Research Foundation) (Grant/Research Support)Entasis (Consultant)F2G (Consultant, Grant/Research Support)German Federal Ministry of Research and Education (Grant/Research Support)Gilead (Consultant, Grant/Research Support)Grupo Biotoscana (Consultant)Immunic (Grant/Research Support)IQVIA (Consultant)Janssen (Grant/Research Support)Matinas (Consultant)Medicines Company (Grant/Research Support)MedPace (Consultant, Grant/Research Support)Melinta Therapeutics (Grant/Research Support)Menarini (Consultant)Merck/MSD (Consultant, Grant/Research Support)Molecular Partners (Consultant)MSG-ERC (Consultant)Mylan (Consultant)Nabriva (Consultant)Noxxon (Consultant)Octapharma (Consultant)Paratek (Consultant)Pfizer (Consultant, Grant/Research Support)PSI (Consultant)Roche Diagnostics (Consultant)Scynexis (Consultant, Grant/Research Support)Seres (Consultant)Shionogi (Consultant)Wiley (Blackwell) (Other Financial or Material Support) Philipp Koehler, MD, Ambu GmbH (Consultant, Speaker’s Bureau)Astellas Pharma (Speaker’s Bureau)Euopean Confederation of Medical Mycology (Speaker’s Bureau)German Federal Ministry of Research and Education (Grant/Research Support)Gilead (Consultant, Speaker’s Bureau)MSD (Speaker’s Bureau)Noxxon N.V. (Consultant)Pfizer (Speaker’s Bureau)State of North Rhine-Westphalia, Germany (Grant/Research Support) Jürgen Prattes, Dr, AbbVie Inc. (Shareholder)Gilead (Speaker’s Bureau)MSD (Grant/Research Support)Novo Nordisk (Shareholder)Pfizer (Advisor or Review Panel member)Stryker (Shareholder) Guenter Weiss, MD, MSD (Speaker’s Bureau)Novartis (Speaker’s Bureau)Pfizer (Speaker’s Bureau)Pharmacosmos (Speaker’s Bureau)Scynexis (Scientific Research Study Investigator)Vifor (Speaker’s Bureau) Nkechi Azie, MD, SCYNEXIS, Inc. (Employee, Shareholder) David A. Angulo, MD, SCYNEXIS, Inc. (Employee, Shareholder)

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686. Elevations in TNFα and IL-18 are Associated with Increased Risk of Probable Cytomegalovirus Tissue Invasive Disease in Solid Organ Transplant Recipients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.878 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S396-S397

Author(s):

Andrew H Karaba ◽

Alexis Figueroa ◽

Stuart C Ray ◽

Robin K Avery ◽

...

Keyword(s):

Viral Load ◽

Research Study ◽

Organ Transplant ◽

Scientific Research ◽

Principal Component ◽

Solid Organ Transplant ◽

Solid Organ ◽

Study Investigator ◽

Cmv Disease ◽

Cmv Dnaemia

Abstract Background Human cytomegalovirus (CMV) continues to cause significant morbidity and mortality in solid organ transplant (SOT) recipients despite prophylaxis. Tissue invasive CMV disease (TI-CMV) can lead to end-organ damage and graft loss. Diagnosing TI-CMV can be challenging as CMV viral load in the blood does not always correlate with episodes of TI-CMV and therefore definitive diagnosis often requires an invasive procedure such as bronchoscopy or colonoscopy. The purpose of this study was to determine if proinflammatory cytokines, including IL-18, are elevated in SOT recipients with probably TI-CMV as a way to identify patients at risk for this severe form of CMV disease. Methods The electronic medical record was searched for adult SOT recipients who were tested for CMV via blood qPCR during an 11-month period.Twenty-nine SOT recipients were identified that had episodes of CMV DNAemia without other concomitant infections during this time period. Patients were divided into those that had probable TI-CMV and those with CMV DNAemia alone, by chart review. Inflammatory cytokines (IFNγ, TNFα, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-18, and IL-1RA) were measured in residual plasma from these patients using a commercially available multiplex assay for at least two time points during the study period. Wilcoxon-Rank-Sum, logistic regression, and principal component analysis was performed comparing patients with and without probable TI-CMV. Results Patients with probable TI-CMV had significantly higher IL-18, TNFα, and IL-1β than patients with CMV DNAemia alone (p < 0.001, < 0.001, and < 0.05 respectively). When adjusting for transplant type and CMV recipient serostatus, elevations in TNFα (OR 1.43, 95% CI 1.07-1.92) and IL-18 (OR 2.00, 95% CI 1.06-3.75) were associated with increased odds of having probable TI-CMV. In principal component analysis the combination of CMV viral load, IL-18, TNFa, and IL-1β accounted for 80% of the variance in the data. Conclusion TNFα and IL-18 in combination with CMV viral load may be useful in predicting likelihood of TI-CMV. This is important in situations where tissue biopsies are not feasible, and adds to our diagnostic capability for TI-CMV in SOT recipients. Disclosures Stuart C. Ray, MD, miDiagnostics, Inc. (Board Member, Research Grant or Support) Robin K. Avery, MD, Aicuris (Scientific Research Study Investigator)Astellas (Scientific Research Study Investigator)Chimerix (Scientific Research Study Investigator)Merck (Grant/Research Support, Scientific Research Study Investigator)Oxford Immunotec (Scientific Research Study Investigator)Qiagen (Scientific Research Study Investigator)Takeda/Shire (Scientific Research Study Investigator)

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75. High Rates of Virologic Suppression with DTG/3TC in Newly Diagnosed Adults with HIV-1 Infection and Baseline Viral Load >500,000 c/mL: 48-Week Subgroup Analysis of the STAT Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.075 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S49-S49

Author(s):

Charlotte-Paige M Rolle ◽

Mezgebe Berhe ◽

Tulika Singh ◽

Roberto Ortiz ◽

Anson K Wurapa ◽

...

Keyword(s):

Viral Load ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Baseline Viral Load ◽

Research Support ◽

Review Panel ◽

Study Investigator ◽

Hiv 1 ◽

Research Grant

Abstract Background The primary analysis of the STAT study demonstrated the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat setting through 24 weeks, with therapy adjustments for baseline resistance or hepatitis B virus (HBV) co-infection. Here we present secondary analyses through Week 48 of virologic outcomes in participants by baseline viral load (VL). Methods STAT is a single-arm study of treatment-naive adults with HIV-1 infection who initiated DTG/3TC ≤ 14 days after HIV-1 diagnosis without availability of screening/baseline laboratory results. If baseline testing indicated DTG or 3TC resistance, HBV co-infection, or creatinine clearance < 30 mL/min/1.73 m2, then antiretroviral therapy (ART) was potentially adjusted and participants remained on study. Efficacy analyses included proportion of participants with HIV-1 RNA < 50 c/mL regardless of ART regimen at Week 48, among all participants (ITT-E missing = failure analysis) and among participants with available HIV-1 RNA data at Week 48 (observed analysis). Results Of 131 enrolled, DTG/3TC treatment was adjusted in 10 participants, and of those with available data (n=7), all (100%) achieved HIV-1 RNA < 50 c/mL at Week 48. At Week 48, 82% (107/131) of all participants (Figure 1) and 97% (107/110) of those with available data (Figure 2) achieved HIV-1 RNA < 50 c/mL. Of participants with baseline VL ≥ 500,000 c/mL, 89% (17/19) achieved HIV-1 RNA < 50 c/mL at Week 48; the remaining 2 withdrew from study. Of participants with baseline VL ≥ 1,000,000 c/mL, 90% (9/10) achieved HIV-1 RNA < 50 c/mL at Week 48 (Table); the remaining participant withdrew consent. Of the 17 participants with baseline VL ≥ 500,000 c/mL with available data through Week 48, 76% (13/17) achieved virologic suppression by Week 24. One participant with baseline VL ≥ 500,000 c/mL switched from DTG/3TC before the Week 48 assessment. Of the 9 participants with baseline VL ≥ 1,000,000 c/mL with available data through Week 48, most participants (8/9; 89%) were suppressed by Week 24. Figure 1. Virologic outcomes at Week 48, overall and by baseline VL and CD4+ cell count: ITT-E missing = failure analysis. Figure 2. Virologic outcomes at Week 48, overall and by baseline VL and CD4+ cell count: observed analysis. Table. Viral Load by Study Visit Among Participants with Baseline HIV-1 RNA ≥1,000,000 c/mL Conclusion These data provide evidence for the efficacy and feasibility of using DTG/3TC as a first-line regimen in a test-and-treat setting, including among participants with very high baseline VL. Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Scientific Research Study Investigator, Advisor or Review Panel member)ViiV Healthcare (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau) Tulika Singh, MD MS AAHIVS, Gilead (Grant/Research Support, Advisor or Review Panel member)ViiV (Grant/Research Support, Advisor or Review Panel member, Speaker's Bureau) Moti Ramgopal, MD FIDSA, Abbvie (Scientific Research Study Investigator, Speaker's Bureau)Gilead (Consultant, Scientific Research Study Investigator, Speaker's Bureau)Janssen (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker's Bureau)Merck (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator, Speaker's Bureau) Dushyantha Jayaweera, MD, mrcog(uk), face, Gilead (Research Grant or Support)Janssen (Research Grant or Support)viiv (Research Grant or Support) Peter Leone, MD, viiv healthcare (Employee) Jessica Matthews, BS, ViiV Healthcare (Employee) Michael Cupo, Ph.D., GlaxoSmithKline (Employee) Mark Underwood, PhD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Kostas Angelis, PhD, GSK (Employee, Shareholder) Brian Wynne, MD, ViiV Healthcare (Employee, Shareholder, I have shares in GSK, the part owner of ViiV) Deanna Merrill, PharmD, MBA, AAHIVP, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Christopher T. Nguyen, MD, ViiV Healthcare (Employee) Jean A. van Wyk, MB,ChB, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Andrew Zolopa, MD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

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1613. Global 2018 Surveillance of Eravacycline Against Gram-negative Pathogens, Including Multi-drug Resistant Isolates

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1793 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S800-S800

Author(s):

Virgil Lijfrock ◽

Steven Morgan ◽

Sara Hwang ◽

Ekaterina Efimova ◽

Kenneth Lawrence ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Vitro Activity ◽

Drug Resistant ◽

In Vitro Activity ◽

Gram Negative ◽

Carbapenem Resistant ◽

Study Investigator ◽

Abdominal Infections

Abstract Background Eravacycline (ERV) is a fully-synthetic, fluorocycline antibacterial approved by the FDA and EMA for treatment of complicated intra-abdominal infections (cIAI) in patients ≥18 years of age. The purpose of this study was to describe the in vitro activity of ERV against Gram-negative pathogens, including multi-drug resistant (MDR) isolates, collected in 2018. Methods Isolates were collected during 2018 from various body sites. Minimum inhibitory concentrations (MICs) were determined by CLSI broth microdilution. Antibiotic susceptibility was determined using the most updated CLSI breakpoints, except for ERV and tigecycline (TGC) where FDA breakpoints established in 2018 and 2005 respectively, were used. MDR was defined as resistance to ≥3 antibiotics from aztreonam, a carbapenem (meropenem or ertapenem [ETP]), cefepime/cefotaxime/ceftazidime/ceftriaxone (any one), gentamicin, levofloxacin, piperacillin-tazobactam TZP, tetracycline or TGC. Results Summary MIC data for ERV and select comparators are shown in the Table. ERV MIC90 for all-Enterobacteriaceae was 0.5 μg/ml and for MDR-Enterobacteriaceae was 1μg/ml. The susceptibilities for all-Enterobacteriaceae were 93%, 95%, 93% and 82% for ERV, TGC, ETP and TZP, respectively. ERV further demonstrated higher rates of susceptibility than ETP and TZP against MDR-Enterobateriaceae, 81% vs 71% vs 38%. ERV MIC50/90 for carbapenem-resistant Acinetobacter baumannii (CRAB) were 4-fold lower than TGC. Table Conclusion ERV in vitro activity was demonstrated and comparable susceptibility rates were observed for clinically important Gram-negative pathogens, including resistant isolates. Overall, ERV MIC90 values were 2- to 8- fold lower than TGC. this study further highlights the in vitro activity of ERV against Gram-negative pathogens identified in patients with cIAI. Disclosures Virgil Lijfrock, PharMD, Tetraphase (Employee) Steven Morgan, PharMD, Tetraphase Pharmaceuticals (Employee) Sara Hwang, PharMD, Tetraphase Pharmaceuticals (Employee) Ekaterina Efimova, PharMD, Tetraphase Pharmaceuticals (Employee) Kenneth Lawrence, PharmD, Tetraphase Pharmaceuticals (Employee) Stephen Hawser, PhD, Tetraphase Pharmaceuticals (Scientific Research Study Investigator) Ian Morrissey, PhD, Tetraphase Pharmaceuticals (Scientific Research Study Investigator)

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561. Safety of Remdesivir vs Standard Care in Patients with Moderate Covid-19

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.755 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S345-S346

Author(s):

Gerard J Criner ◽

Mi Young Ahn ◽

Gregory Huhn ◽

Aruna Subramanian ◽

...

Keyword(s):

Research Study ◽

Safety Data ◽

Scientific Research ◽

Standard Of Care ◽

Liver Function Tests ◽

Similar Rate ◽

Research Support ◽

Open Label ◽

Study Investigator ◽

Open Label Phase

Abstract Background Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Here we report safety of RDV in patients with moderate COVID-19. Methods We conducted an open-label, phase 3 trial (NCT04252664) in hospitalized patients with confirmed SARS-CoV-2 infection, evidence of pulmonary infiltrates, and oxygen saturation >94% on room air. Patients were randomly assigned to receive RDV (5 or 10 days) or standard of care (SOC). RDV was dosed intravenously at 200 mg on day 1, 100 mg daily thereafter. Adverse events (AEs) and laboratory abnormalities were evaluated through the day 11 data cut; safety data through day 28 will be presented at the meeting. Results 584 patients were randomized and treated (5d RDV: n=191; 10d RDV, n=193; SOC: n=200). Baseline characteristics were balanced among groups; median (range) age was 57y (12-95y), 39% were female and 19% Black, 39% had arterial hypertension, 15% hyperlipidemia, 11% asthma. Briefly, across both the 5d and 10d arms, RDV was well tolerated with a similar rate of Grade 3 or 4 AEs and fewer SAEs compared to SOC (Table). AEs more common with RDV vs SOC included nausea, headache, and hypokalemia. Overall, across the 3 arms, incidence of AEs leading to discontinuation and death were low and no clinically relevant changes in laboratory parameters were observed. In addition, median changes in renal and liver function tests from baseline were not statistically significant between the RDV 5d and RDV 10d groups compared to the SOC only group at d14 (Table 1). Table 1. Conclusion RDV given for 5d or 10d was well tolerated in patients with moderate COVID-19. No clinically significant safety signals were observed with RDV vs SOC. Disclosures Gerard J. Criner, MD, Gilead Sciences Inc. (Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator) Gerard J. Criner, MD, NO DISCLOSURE DATA Mi Young Ahn, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Gregory Huhn, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator)Janssen (Grant/Research Support)Proteus (Grant/Research Support)US National Institutes of Health (Grant/Research Support)Viiv Healthcare (Grant/Research Support) Aruna Subramanian, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Carlos Lumbreras, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Stefan Schmiedel, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Robert H. Hyland, MD, Gilead Sciences Inc. (Employee, Shareholder) Vithika Suri, PhD, Gilead Sciences Inc. (Employee, Shareholder) Huyen Cao, MD, Gilead Sciences Inc. (Employee, Shareholder) Hongyuan Wang, PhD, Gilead Sciences Inc. (Employee, Shareholder) Devi SenGupta, MD, Gilead Sciences Inc. (Employee, Shareholder) Anand Chokkalingam, PhD, Gilead Sciences (Employee) Anu Osinusi, MD, Gilead Sciences (Employee) Diana M. Brainard, MD, Gilead Sciences (Employee) Yao-Shen Chen, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Yao-Shen Chen, MD, NO DISCLOSURE DATA Huldrych Günthard, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) D Jose Sanz-Moreno, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Judith A. Aberg, MD, Theratechnology (Consultant) Emanuele Nicastri, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Owen Tak-Yin Tsang, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Owen Tak-Yin Tsang, MD, NO DISCLOSURE DATA

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1351. Use of Mail-Out Sexually Transmitted Infection Test Kits in a Telehealth Pre-exposure Prophylaxis Clinic

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1543 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S762-S762

Author(s):

Monica K Sikka ◽

Long Do ◽

Hanifa Ha ◽

Dana Smothers ◽

Christopher Evans ◽

...

Keyword(s):

Research Study ◽

Vaccine Trial ◽

Scientific Research ◽

Standard Of Care ◽

Patient Comfort ◽

Care Practice ◽

Transmitted Infection ◽

Sexually Transmitted ◽

Study Investigator ◽

Exposure Prophylaxis

Abstract Background Standard of care for patients receiving pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) includes HIV screening and testing for sexually transmitted infections (STIs) at all sites of potential exposure every three months. We implemented a provider and pharmacist telehealth based PrEP program as part of the HIV, Hepatitis Specialty Telehealth Access Resource (H-START) Collaborative. Due to the COVID-19 pandemic and care via telehealth, we had limited ability to collect pharyngeal or rectal swabs in clinic. We created mail-out kits including swabs and instructions for self-collection to test for rectal and pharyngeal Neisseria gonorrhea and Chlamydia trachomatis. Methods Kits were mailed out to patients between June 2020 and May 2021. Providers first confirmed patient comfort with self-swab collection during telehealth appointments. Kits included: an instruction sheet with visual diagrams for collection, swabs with appropriate labels; and a pre-paid envelope for patients to mail swabs back to our facility for laboratory testing. Prospective data collection included the date kits were mailed out to patients, the date of kit receipt at our facility and the test result. Charts were retrospectively reviewed to determine treatment completion. Results 54 self-swab kits were mailed to patients. 53 of the patients were male and the average age was 41.3 years old. 38 (70.3%) swabs were returned. The median time for return of swabs was 21 days (Range 2-289). Of those returned, 5 (13.1%) were positive and all 5 patients were treated for their infection. Conclusion Mail-out STI testing was effective in identifying STIs for a telehealth PrEP program and for maintaining standard of care practice during the COVID-19 pandemic. This model may increase rates of testing compliance for care provided via telehealth and decrease rates of STI transmission and complications. Better communication around returning kits in a timely-manner and understanding reasons for non-return warrant further investigation. Disclosures Monica K. Sikka, MD, FG2 (Scientific Research Study Investigator) Christopher D. Pfeiffer, MD, MHS, C. difficile Vaccine Trial (Scientific Research Study Investigator)

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