scholarly journals Detecting Infections Rapidly and Easily for Candidemia Trial (DIRECT1): A Prospective, Multicenter Study of the T2Candida Panel

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S52-S52
Author(s):  
Cornelius J Clancy ◽  
Peter Pappas ◽  
Jose Vazquez ◽  
Marc A Judson ◽  
Ellis Tobin ◽  
...  
Keyword(s):  
Blood Cultures ◽  
Important Advance ◽  
Research Support ◽  
Prospective Multicenter Study ◽  
Indwelling Catheters ◽  
Blood Samples ◽  
Grant Recipient ◽  
Mean Time ◽  
Research Grant

Abstract Background Blood cultures (BC) are the diagnostic gold standard for candidemia, but sensitivity is <50%. T2 Candida (T2) is a novel, FDA-approved nanodiagnostic panel, which utilizes T2 magnetic resonance and a dedicated instrument to detect Candida within whole blood samples. Methods Candidemic adults were identified at 14 centers by diagnostic BC (dBC). Follow-up blood samples were collected from all patients (pts) for testing by T2 and companion BC (cBC). T2 was run-in batch at a central lab; results are reported qualitatively for three groups of spp. (Candida albicans/C. tropicalis (CA/CT), C. glabrata/C. krusei (CG/CK), or C. parapsilosis (CP)). T2 and cBC were defined as positive (+) if they detected a sp. identified in dBC. Results 152 patients were enrolled (median age: 54 yrs (18–93); 54% (82) men). Candidemia risk factors included indwelling catheters (82%, 125), abdominal surgery (24%, 36), transplant (22%, 33), cancer (22%, 33), hemodialysis (17%, 26), neutropenia (10%, 15). Mean times to Candida detection/spp. identification by dBC were 47/133 hours (2/5.5 d). dBC revealed CA (30%, 46), CG (29%, 45), CP (28%, 43), CT (11%, 17) and CK (3%, 4). Mean time to collection of T2/cBC was 62 hours (2.6 d). 74% (112) of patients received antifungal (AF) therapy prior to T2/cBC (mean: 55 hours (2.3 d)). Overall, T2 results were more likely than cBC to be + (P < 0.0001; Table), a result driven by performance in AF-treated patients (P < 0.0001). T2 was more likely to be + among patients originally infected with CA (61% (28) vs. 20% (9); P = 0.001); there were trends toward higher positivity in patients infected with CT (59% (17) vs. 23% (4; P = 0.08) and CP (42% (18) vs. 28% (12); P = 0.26). T2 was + in 89% (32/36) of patients with + cBC. Conclusion T2 was sensitive for diagnosing candidemia at the time of + cBC, and it was significantly more like to be + than cBC among AF-treated patients. T2 is an important advance in the diagnosis of candidemia, which is likely to be particularly useful in patients receiving prophylactic, pre-emptive or empiric AF therapy. Disclosure D. P. Kontoyiannis, Pfizer: Research Contractor, Research support and Speaker honorarium; Astellas: Research Contractor, Research support and Speaker honorarium; Merck: Honorarium, Speaker honorarium; Cidara: Honorarium, Speaker honorarium; Amplyx: Honorarium, Speaker honorarium; F2G: Honorarium, Speaker honorarium; L. Ostrosky-Zeichner, Astellas: Consultant and Grant Investigator, Consulting fee and Research grant; Merck: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium; Pfizer: Grant Investigator and Speaker’s Bureau, Grant recipient and Speaker honorarium; Scynexis: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient; Cidara: Grant Investigator and Scientific Advisor, Consulting fee and Research grant; S. Apewokin, T2 biosystems: Investigator, Research support; Astellas: Scientific Advisor, Consulting fee

scholarly journals 814. Successful Treatment of Cutibacterium acnes (CA) Prosthetic Device Infection (PDI) with Oral Linezolid and Rifampin (LR)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S500-S500
Author(s):  
Ronald G Nahass ◽  
Maalikat Esquivel ◽  
Krystle Smith ◽  
Danielle Heinemann ◽  
Kathleen H Seneca
Keyword(s):  
Low Cost ◽  
Oral Treatment ◽  
Prosthetic Device ◽  
Research Support ◽  
Duration Of Treatment ◽  
Slime Layer ◽  
Device Infection ◽  
Cutibacterium Acnes ◽  
Research Grant

Abstract Background CA PDI is increasingly recognized. CA is felt to create a slime layer that makes infection more likely and treatment more difficult in this setting. Traditional management has included prosthetic device explantation (PDE), prolonged antibiotic treatment, and delayed reimplantation. Recent interest in the use of oral treatment regimens and single stage procedures with long duration antibiotic therapy led us to treat a series of patients with oral treatment and retained prosthesis after debridement. We report those results. Methods Sequential patients with CA PDI treated with oral therapy were identified. All patients underwent debridement of the tissue, exchange of components and/or reimplantation of the prosthetic device. Only patients with exchanges were included. PDE was excluded. MIC testing for CA isolates was obtained when possible. Initial treatment was recorded at time of surgery. LR was the treatment of choice unless toxicity developed. A minimum of a 3-month follow-up post treatment was required to be included. 6 and 12 month follow up were obtained for all patients but 1 at this time. Results 10 patients were treated (Table 1). Shoulder joint infections were most common. All patients were treated with LR. All completed a minimum of 42 days of treatment (Table 2). The medication was well tolerated. The most common adverse events were nausea. 9/10 patients with 12 month follow up had no evidence of relapse. 1/10 had no relapse at 3 months. Typical for CA infection laboratory markers for infection were not markedly elevated. Notably thrombocytopenia did not occur (Table 3). Table 1. Distribution of Prosthetic Device Infections Table 2. Duration of Treatment Table 3. Selected Laboratory Results Conclusion We demonstrated the ability to successfully treat 10/10 patients with CA PDI without explantation using prolonged oral treatment with LR after debridement. This combination should be considered a treatment option and explored further as a low cost, well tolerated, high value treatment approach to this difficult infection. Disclosures Ronald G. Nahass, MD, Abbvie (Grant/Research Support, Speaker’s Bureau)Alkermes (Grant/Research Support)Gilead (Grant/Research Support, Speaker’s Bureau)Merck (Grant/Research Support, Speaker’s Bureau) Kathleen H. Seneca, MSN, Abbvie (Research Grant or Support)Alkermes (Research Grant or Support)Gilead (Speaker’s Bureau)

scholarly journals 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

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S65-S65 ◽  
Author(s):  
Joseph Eron ◽  
Chloe Orkin ◽  
Douglas Cunningham ◽  
Federcio Pulido ◽  
Frank Post ◽  
...  
Keyword(s):  
Extension Phase ◽  
Virologic Suppression ◽  
Efficacy And Safety ◽  
Research Support ◽  
Open Label ◽  
Genetic Barrier ◽  
Independent Contractor ◽  
Grant Recipient ◽  
Hiv 1 ◽  
Research Grant

Abstract 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.

scholarly journals 11. Evaluation of the Bact/alert® VIRTUO™ in Terms of Time to Detection, Performance, Workflow Efficiency and Impact on Patient Management, Compared to the BACTEC™ FX Automated Blood Culture System

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S7-S7
Author(s):  
Ana V Halperin ◽  
José Luis Cortés Cuevas ◽  
Juan Antonio Del Castillo Polo ◽  
Miriam Cuesta ◽  
Sergio Talens ◽  
...  
Keyword(s):  
Blood Culture ◽  
Large Scale ◽  
Clinical Performance ◽  
Bloodstream Infections ◽  
Blood Cultures ◽  
Causative Organism ◽  
Research Support ◽  
Hands On ◽  
Time To Detection ◽  
Research Grant

Abstract Background Bloodstream infections are associated with high rates of morbidity and mortality, therefore prompt identification and antimicrobial susceptibility testing of the causative organism(s) are critical. We compared the microbiological/clinical performance of BacT/ALERT®-VIRTUO™-(BioMerieux) to that of the BACTEC™FX-(BD) instrument, with time-to-detection (TTD, from loading into system until positivity) as the primary outcome. Secondary microbiological outcomes were positivity and contamination rates, hands-on-time, turn-around-time (TAT) and time-to-identification. Methods We performed a prospective cross-over study using blood cultures from patients (>18 years) suspected of bacteremia/fungemia, localized in different wards into two strata (Stratum-1: Emergency Department-ED-; Stratum-2: in-hospital patients). Testing was performed in BACTEC™-PlusAerobic/F and BACTEC-Lytic/10-Anaerobic/F bottles and incubated in BACTEC™FX, or BacT/ALERT®FA-Plus and FN-Plus bottles and incubated in VIRTUO™. Initially, each strata was randomly assigned to one of the incubators and then alternated every 2-weeks for 6 months (October-16th-2018 to April-16th-2019). All samples were processed in parallel with the same work-flow from the moment they were flagged positive. Maximum incubation time was 5 days. Results We included a total of 4782 extractions (9510 bottles) in VIRTUO and 5139 (10193 bottles) in BACTEC. The median age was 67 years for both groups and the samples were equally distributed for each ward (ED: VIRTUO 80.9%, BD 76.4%). The number of blood cultures with at least one positive extraction was 873(18.3%) for VIRTUO and 802(15.6%) for BACTEC (p=0.0003). TTD and proportion of aerobic/anaerobic bottles is shown in Table. Hands-on-time was reduced by 15 minutes/day when using VIRTUO. Table Conclusion We have compared on a large scale and in a “real world” setting the performance of two automatic blood culture incubators. TTD was significantly lower for the VIRTUO incubated samples, with differences in both systems depending on the type of bottle (aerobic vs. anaerobic). The number of positive results was significantly higher for the VIRTUO incubated samples, which might impact antimicrobial prescription and clinical outcomes. Disclosures Ana V. Halperin, MD, Biomérieux (Grant/Research Support) José Luis Cortés Cuevas, MD, biomerieux (Research Grant or Support)biomerieux (Research Grant or Support) Juan Antonio Del Castillo Polo, MD, Biomérieux (Research Grant or Support) Sergio Talens, n/a, Biomerieux (Research Grant or Support) Robert Birch, n/a, bioMerieux Inc. (Employee) Rafael Cantón, PharmD PhD, Biomérieux (Grant/Research Support)

scholarly journals 127. Development of a Kinetic ELISA (kELISA) and Reactive B-cell Frequency (RBF) Assay to Detect Respiratory Syncytial Virus (RSV) Pre-Fusion F Protein-Specific Immune Responses in Infants

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S77-S78
Author(s):  
Stephanie L Rolsma ◽  
Sandy M Yoder ◽  
Rachel S Nargi ◽  
Eric Brady ◽  
Natalia Jimenez-Truque ◽  
...  
Keyword(s):  
Panel Member ◽  
Multiple Time ◽  
Research Support ◽  
Review Panel ◽  
Cell Frequency ◽  
Material Support ◽  
F Protein ◽  
Multiple Time Points ◽  
Research Grant

Abstract Background RSV is a major cause of pediatric respiratory disease. Antibodies to the prefusion conformation of the RSV fusion (pre-F) protein are needed for virus neutralization. Methods We measured RSV-specific responses in two groups of children < 3 years of age; subjects with laboratory-confirmed RSV (RSV-infected) or infants born in the period May to September and enrolled prior to their first RSV season (RSV-uninfected). RSV-infected infants had blood samples obtained at 1, 6, 9, and 12 months after infection. RSV-uninfected infants had blood samples obtained at enrollment, at the end of their first RSV season, and 6 months later. A kELISA to measure RSV pre-F-specific antibodies and an RBF assay to identify RSV F-specific B cells were developed. Results 102 subjects were enrolled; 11 were excluded due to missed visits or withdrawal. Of the 65 subjects in the RSV-uninfected group, all were kELISA positive at enrollment, consistent with maternal antibody transfer. 53 subjects had sufficient samples for analysis at multiple time points; 29 became seronegative and 24 remained seropositive. In the seronegative group, the kELISA value decreased rapidly to < 0.25 by 6 months after the RSV season in 27/29 (93%), (Figure 1a). In the persistently seropositive group, all 24 subjects maintained a positive kELISA value, with some developing higher values over time, consistent with asymptomatic infection (Figure 1b). An RBF assay was used to determine whether antibodies were due to persistent maternal antibodies or endogenous production (Figure 2). In the seronegative group, 24/29 (80%) had a negative RBF; in the seropositive group, 23/24 (96%) had a positive RBF during follow-up. There were 26 subjects in the RSV-infected group; 22 had sufficient samples for analysis at multiple time points. All were seropositive by kELISA at one month post-infection with variable kELISA values during follow-up (Figure 3). 17/22 (77%) had a positive RBF, although 4 of the subjects without a positive RBF had indeterminate results at ≥ 1 visit. Figure 1. kELISA values of baseline RSV-negative subjects, by subject age at time of sample. Panel A: Subjects classified as seronegative (n=29). Panel B: Subjects without known RSV classified as persistently seropositive (n=24). Figure 2. Reactive B-cell frequency assay. The first step in the RBF assay is growth of Lymphoblastoid Cell Lines (LCLs), as shown over days 1-3 (Left-Day 1, Middle-Day 2, Right-Day 3, magnification 200X). The cells circled in the figure indicate a single LCL’s growth over time. LCL supernatant is used to detect RSV F-protein specific antibodies using traditional ELISA, resulting in a positive, indeterminate, or negative result. Indeterminate results occur due to a lack of cell viability and/or failure to form LCLs, resulting in failure to exceed an optical density of 5x background. Figure 3. kELISA values of RSV-infected subjects, by subject age at time of sample. First sample was obtained at approximately one month after laboratory-confirmed RSV. Conclusion Assays measuring F-specific immune responses in infants will be critical for RSV vaccine development. A kELISA targeting RSV pre-F epitopes, with an RBF assay targeting RSV F-specific B cells, may allow discrimination for maternal and infant-derived antibodies. Disclosures Isaac Thomsen, MD, MSCI, Horizon Therapeutics (Individual(s) Involved: Self): Consultant James E. Crowe, Jr., MD, Astra Zeneca (Grant/Research Support)IDBiologics (Board Member, Grant/Research Support, Shareholder)Luna Biologics (Consultant)Meissa Vaccines (Advisor or Review Panel member)Takeda Vaccines (Grant/Research Support) Kathryn M. Edwards, MD, Bionet (Individual(s) Involved: Self): Consultant; CDC (Individual(s) Involved: Self): Research Grant or Support; IBM (Individual(s) Involved: Self): Consultant; Merck (Individual(s) Involved: Self): member DSMC, Other Financial or Material Support; Moderna (Individual(s) Involved: Self): member DSMC, Other Financial or Material Support; NIH (Individual(s) Involved: Self): Research Grant or Support; Pfizer (Individual(s) Involved: Self): member DSMC, Other Financial or Material Support; Roche (Individual(s) Involved: Self): member of DSMB, Other Financial or Material Support; Sanofi Pasteur (Individual(s) Involved: Self): member DSMB, Other Financial or Material Support; Sequiras (Individual(s) Involved: Self): Member DSMB, Other Financial or Material Support; X4 Pharmaceuticals (Individual(s) Involved: Self): Consultant Buddy Creech, MD, MPH, Altimmune (Consultant)Astellas (Other Financial or Material Support, Data and Safety Monitoring Committee)Diotheris (Consultant)GSK (Consultant)Horizon (Consultant)Merck (Scientific Research Study Investigator)Premier Healthcare (Advisor or Review Panel member)Vir (Consultant)

scholarly journals 67. SARS-CoV-2 Transmission: Preliminary Findings from a Household-based Study

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S165-S165
Author(s):  
Carlos G Grijalva ◽  
Yuwei Zhu ◽  
Natasha B Halasa ◽  
Ahra Kim ◽  
Melissa A Rolfes ◽  
...  
Keyword(s):  
Disease Onset ◽  
Median Number ◽  
Household Member ◽  
Research Support ◽  
Nasal Swabs ◽  
Household Members ◽  
Index Cases ◽  
Support Research ◽  
Research Grant

Abstract Background Social distancing measures, such as shelter-in-place or stay-at-home orders, are recommended for control of community transmission of SARS-CoV-2. Few studies, however, have characterized the transmission of SARS-CoV-2 infections in households. Methods We conducted a case-ascertained study of household transmission in Nashville, TN starting in April 2020, after recommendations to stay at home were enacted. Index cases were ambulatory patients identified through clinical RT-PCR testing at Vanderbilt walk-in-clinics dispersed across the Nashville metropolitan area. For this study, the index case was the first person presenting with respiratory or compatible symptoms in a household and who lived with at least one other household member. After informed consent was obtained, household members were remotely trained in the self-collection of nasal swabs and use of REDCap electronic questionnaires. Household members completed daily symptom diaries and collected daily nasal swabs for 14 days. Contact patterns within households before and after disease onset were ascertained. Nasal swab samples were tested using RT-PCR at an academic research laboratory. Results At the time of writing, 18 families were enrolled (including 18 index cases and 34 household members) with at least 1 follow-up nasal swab tested. The median age of index cases and household members was 37 years (IQR: 26–46) and 27 years (15–39), respectively. The median number of days from index patient onset of symptoms to first sample collected in the household was 4 (2–5). Before onset of symptoms, 83% of index cases spent >4 hours in the same room with at least one other household member, whereas after disease onset and diagnosis, 44% did. Among 34 non-index household members, 18 (53%) had a positive test during follow-up; the median number of days from index case’s symptoms onset to first positive detection in a household member was 4.5 (3–5) days. Interestingly, 13 (72%) of 18 secondary infections were detected within the first 3 days of follow-up, whereas 5 (28%) were detected during subsequent days. Conclusion These observations suggest that transmission of SARS-CoV-2 within households is high, with many infections detected during the initial days of study follow-up. Disclosures Carlos G. Grijalva, MD, MPH, AHRQ (Grant/Research Support)Campbell Alliance (Grant/Research Support)CDC (Grant/Research Support)FDA (Grant/Research Support)Merck (Consultant)NIH (Scientific Research Study Investigator)Pfizer (Consultant)Sanofi (Consultant)Sanofi (Grant/Research Support) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support)

scholarly journals 358. Sociodemographic and clinical features of children and adolescents with SARS-CoV-2 infection in Nashville, Tennessee

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S248-S249
Author(s):  
Leigh Howard ◽  
Kathryn Garguilo ◽  
Jessica Gillon ◽  
Steven Webber ◽  
Natasha B Halasa ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Research Support ◽  
Full Spectrum ◽  
Duration Of Symptoms ◽  
Healthcare Settings ◽  
Asymptomatic Children ◽  
Asymptomatic Patients ◽  
Support Research ◽  
Research Grant

Abstract Background Little is known regarding the full spectrum of illness among children with SARS-CoV-2 infection across integrated healthcare settings, as many published pediatric cohorts focus on hospitalized patients with SARS-CoV-2 infection. Methods Active surveillance was performed for SARS-CoV-2 detections among symptomatic and asymptomatic children and adolescents ≤18 years of age in a quaternary care academic hospital laboratory in the Southeastern U.S. For symptomatic patients with a positive respiratory specimen for SARS-CoV-2 by polymerase chain reaction (PCR), and for neonates born to SARS-CoV-2-positive mothers, we performed phone follow-up and medical record review at days 2, 7, and 30 after diagnosis. Testing was initiated 3/12/20 for symptomatic patients and 5/4/20 for screening asymptomatic patients. Results By 6/14/20, SARS-CoV-2 tests were positive in 193/5306 (3.6%) specimens from unique patients ≤18 (Table 1), compared to 2653/36503 (7.2%) specimens in patients >18 years. Specimens from 181/2638 (6.8%) symptomatic and 12/2768 (0.4%) asymptomatic children were positive. Nine infants born to SARS-CoV-2 infected mothers had negative PCR tests at birth; 1 infant subsequently acquired SARS-CoV-2 infection at 5 weeks of age. Sociodemographic and clinical data for 181 SARS-CoV-2-positive symptomatic children are displayed in Table 2 and Figure 1. The most common symptoms were cough (59%), fever (50%), and rhinorrhea (39%). Nine/181 symptomatic patients (5%) were hospitalized, primarily for respiratory symptoms. Symptom resolution occurred by follow-up day 2 in 82/178 (46%) and day 7 in 128/164 (78%) patients with complete assessments to date. 131/181 (72%) of children had known SARS-CoV-2 positive contacts. We observed no cases of multisystem inflammatory syndrome in children. Conclusion In our community, pediatric SARS-CoV-2 prevalence was low, but was much higher among symptomatic than asymptomatic children. Symptoms were mild, and the duration of symptoms brief, in the majority of these patients captured within an integrated ambulatory and hospital-based healthcare system, capturing the full spectrum of the disease profile in this age group. Disclosures Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support)

scholarly journals LB13. The Efficacy and Impact in Heathy Infants of Nirsevimab on Medically Attended RSV Lower Respiratory Tract Infection

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S811-S812
Author(s):  
Laura Hammitt ◽  
Laura Hammitt ◽  
Ron Dagan ◽  
Yuan Yuan ◽  
Manuel Baca Cots ◽  
...  
Keyword(s):  
Research Study ◽  
Scientific Research ◽  
Panel Member ◽  
Research Support ◽  
Review Panel ◽  
Term Infants ◽  
Study Investigator ◽  
Support Research ◽  
Research Grant

Abstract Background Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) in infants. Nirsevimab is a single-dose monoclonal antibody with extended half-life that was shown to protect preterm infants 29 to < 35 weeks gestation against RSV LRTI. However, most medically attended (MA) cases occur in otherwise healthy, term infants for whom there is currently no effective RSV prevention strategy. We report the primary analysis of efficacy and safety, along with the impact of nirsevimab in late preterm and term infants (≥ 35 weeks gestation) in the phase 3 MELODY study (NCT03979313). Methods Infants were randomized 2:1 to receive one intramuscular injection of nirsevimab (50 mg if < 5 kg; 100 mg if ≥ 5 kg at dosing) or placebo entering their first RSV season. The primary endpoint was the incidence of MA RSV LRTI over 150 days postdose. Cases met predefined clinical criteria of disease severity and were confirmed by real-time reverse-transcriptase PCR. Safety was evaluated through 360 days postdose. Enrollment started on 23 July 2019 and was suspended following the declaration of the COVID-19 pandemic by the WHO on 11 March 2020. Results Overall, 1490 infants were randomized and included in the intent-to-treat population; 1465 (98%) completed the 150-day efficacy follow-up, and 1367 (92%) completed the 360-day safety follow-up. The incidence of MA RSV LRTI was 1.2% (n=12/994) in the nirsevimab group and 5.0% (n=25/496) in the placebo group, giving nirsevimab an efficacy of 74.5% (95% confidence interval [CI]: 49.6, 87.1; p< 0.0001). Nirsevimab averted 93.6 (95% CI 63.0, 124.0) MA LRTIs per 1000 infants dosed. Nirsevimab was well tolerated, with similar rates of adverse events (87.4% nirsevimab; 86.8% placebo) and serious adverse events (6.8% nirsevimab; 7.3% placebo) between groups. Conclusion In this phase 3 study, a single dose of nirsevimab protected late preterm and term infants against MA RSV LRTI over an RSV season with a favorable safety profile. Approximately 11 infants need to be immunized to prevent 1 case of LRTI; nirsevimab has the potential to be an important intervention to reduce the burden of RSV LRTI in healthy infants. Disclosures Laura Hammitt, MD, MedImmune (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Merck & Co., Inc. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Novavax (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Laura Hammitt, MD, MedImmune (Individual(s) Involved: Self): Grant/Research Support, Research grant to my institution; Merck (Individual(s) Involved: Self): Grant/Research Support, Research grant to my institution; Pfizer (Individual(s) Involved: Self): Grant/Research Support, Research grant to my institution Ron Dagan, MD, Medimmune/AstraZeneca (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)MSD (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau) Yuan Yuan, PhD, AstraZeneca (Employee, Shareholder) Shabhir A. Mahdi, PhD, BMGF (Research Grant or Support)EDCTP (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melody (Research Grant or Support)Minervax (Research Grant or Support)Novavax (Research Grant or Support)SAMRC (Research Grant or Support) William J. Muller, MD, PhD, Ansun (Scientific Research Study Investigator)Astellas (Scientific Research Study Investigator)AstraZeneca (Scientific Research Study Investigator)Genentech (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Janssen (Scientific Research Study Investigator)Karius (Scientific Research Study Investigator)Melinta (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator)Nabriva (Scientific Research Study Investigator)Seqirus (Scientific Research Study Investigator)Tetraphase (Scientific Research Study Investigator) William J. Muller, MD, PhD, Ansun (Individual(s) Involved: Self): Grant/Research Support; Astellas (Individual(s) Involved: Self): Research Grant or Support; AstraZeneca (Individual(s) Involved: Self): Grant/Research Support; BD (Individual(s) Involved: Self): Research Grant or Support; Eli Lilly (Individual(s) Involved: Self): Grant/Research Support; Gilead (Individual(s) Involved: Self): Grant/Research Support; Karius, Inc. (Individual(s) Involved: Self): Grant/Research Support, Scientific Research Study Investigator; Melinta (Individual(s) Involved: Self): Grant/Research Support; Merck (Individual(s) Involved: Self): Grant/Research Support; Moderna (Individual(s) Involved: Self): Grant/Research Support; Nabriva (Individual(s) Involved: Self): Grant/Research Support; Seqirus (Individual(s) Involved: Self): Consultant; Tetraphase (Individual(s) Involved: Self): Grant/Research Support Heather J. Zar, PhD, AstraZeneca (Grant/Research Support)Novavax (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member) Dennis Brooks, MD, AstraZeneca (Employee) Amy Grenham, MSc, AstraZeneca (Employee, Shareholder) Ulrika Wählby Hamrén, PhD, AstraZeneca R&D (Employee, Shareholder) Vaishali S. Mankad, MD, AstraZeneca (Employee) Therese Takas, BSc, AstraZeneca (Employee, Other Financial or Material Support, Own stock in AstraZeneca) Jon Heinrichs, PhD, AstraZeneca (Shareholder)Bristol Myers Squibb (Shareholder)J&J (Shareholder)Merck (Shareholder)Organon (Shareholder)Procter & Gamble (Shareholder)Sanofi (Shareholder)Sanofi Pasteur (Employee) Amanda Leach, MRCPCH, AstraZeneca (Employee, Shareholder) M. Pamela Griffin, MD, AstraZeneca (Employee) Tonya L. Villafana, PhD, AstraZeneca (Employee)

scholarly journals 854. Long-term Outcomes of Participants on F/TAF for Pre-Exposure Prophylaxis: Results for 144 Weeks of Follow-Up in the DISCOVER Trial

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S517-S518
Author(s):  
Moti Ramgopal ◽  
Peter Ruane ◽  
Yongwu Shao ◽  
Ramin Ebrahimi ◽  
Alex Kintu ◽  
...  
Keyword(s):  
Research Study ◽  
Scientific Research ◽  
Panel Member ◽  
Mineral Density ◽  
Research Support ◽  
Review Panel ◽  
Study Investigator ◽  
Research Grant

Abstract Background In DISCOVER, a multinational randomized controlled trial, F/TAF demonstrated noninferior efficacy compared to F/TDF for HIV prevention with improved bone mineral density and renal safety biomarkers at the primary endpoint (when all participants had reached 48 weeks and 50% had reached 96 weeks) and at week (W) 96, the end of the blinded phase. We now report W144 outcomes for participants who were randomized to F/TAF and continued F/TAF in the open-label extension (OLE) phase. Methods All participants who completed the randomized blinded phase could opt to receive F/TAF for at least 48 weeks in the OLE phase. We evaluated HIV incidence in participants on F/TAF through W144 and assessed changes in hip and spine bone mineral density (BMD) and in glomerular function (eGFR) from baseline to W144. Results 2,080 of the 2,694 participants initially randomized to F/TAF opted into the OLE phase, and 1,933 were still on study drug through W144, thereby leading to a total of 7,885 person-years (PY) of follow-up on F/TAF. Eight participants taking F/TAF acquired HIV in the blinded phase and 3 in the OLE phase. Dried blood spot analyses on the 3 OL infections found tenofovir diphosphate levels consistent with low adherence. Genotypic resistance testing showed no relevant resistance mutations for the 3 new infections. Among participants taking F/TAF, HIV incidence was 0.16/100 PY (95% CI 0.06-0.33) at the primary endpoint, 0.16/100 PY (95% CI 0.07-0.31) through 96 weeks and 0.14/100 PY (95% CI 0.07-0.25) through 144 weeks. Participants taking F/TAF had increases in hip BMD (mean percentage change +0.54%) and in spine BMD (mean percentage change +1.02%) from baseline to W144 (Figure 1). Median eGFR increased over 144 weeks, with a median increase of 2.6 mL/min from baseline to week 144. Participants in the F/TAF arm gained a median 2.3 kg (IQR -0.9-5.8) over 3 years of follow up. Figure 1. Changes in hip and spine bone mineral density and in eGFR through Week 144 Conclusion The OLE of DISCOVER allowed for a long-term assessment (144 wks.) of F/TAF for PrEP. HIV incidence remained low with BMD and renal function parameters remaining stable through 144 weeks of follow-up. These findings demonstrate that F/TAF is a safe and effective option for long-term use in people who would benefit from PrEP. Disclosures Moti Ramgopal, MD FACP 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) Peter Ruane, MD, AbbVie (Consultant, Research Grant or Support)Allergan (Research Grant or Support)Gilead Sciences Inc. (Consultant, Research Grant or Support, Shareholder, Speaker’s Bureau)Merck (Consultant, Research Grant or Support)ViiV Healthcare (Consultant, Research Grant or Support) Yongwu Shao, PhD, Gilead Sciences Inc. (Employee, Shareholder) Ramin Ebrahimi, MSc, Gilead Sciences Inc. (Employee, Shareholder) Alex Kintu, MD, ScD, Gilead Sciences Inc. (Employee, Shareholder) Christoph C. Carter, MD, Gilead Sciences Inc. (Employee, Shareholder) Moupali Das, MD, Gilead Sciences Inc. (Employee, Shareholder) Jared Baeten, MD, PHD, Gilead Sciences Inc. (Employee, Shareholder) Cynthia Brinson, MD, Abbvie (Scientific Research Study Investigator)BI (Scientific Research Study Investigator)Gilead Sciences Inc. (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau, Personal fees)GSK (Scientific Research Study Investigator)Novo Nordisk (Scientific Research Study Investigator)ViiV Healthcare (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau) Peter Shalit, MD, PhD, Abbvie (Grant/Research Support)Gilead Sciences (Consultant, Grant/Research Support, Speaker’s Bureau)Glaxo Smithkline (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support, Speaker’s Bureau)Merck (Grant/Research Support, Speaker’s Bureau)Thera (Speaker’s Bureau)ViiV Healthcare (Speaker’s Bureau) Karam Mounzer, MD, Epividian (Advisor or Review Panel member)Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker’s Bureau)Janssen (Consultant, Research Grant or Support, Speaker’s Bureau)Merck (Research Grant or Support, Speaker’s Bureau)ViiV Healthcare (Consultant, Speaker’s Bureau)

scholarly journals Viral Failure Among Persons Living with HIV Initiating Dolutegravir-Based vs. Other Recommended Regimens in Real-World Clinical Care Settings

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S39-S39 ◽  
Author(s):  
Robin Nance ◽  
Vani Vannappagari ◽  
Kimberly Smith ◽  
Catherine Johannes ◽  
Brian Calingaert ◽  
...  
Keyword(s):  
Viral Load ◽  
Clinical Care ◽  
The United States ◽  
Sensitivity Analyses ◽  
Research Support ◽  
Hiv Viral Load ◽  
Persons Living With Hiv ◽  
Grant Recipient ◽  
Living With Hiv

Abstract Background Much of the prior research on viral failure (VF) with integrase inhibitor (INSTI) therapy is based on results from trials rather than clinical care settings and little is known about recently approved medications such as dolutegravir (DTG). We compared VF in persons living with HIV (PLWH) who initiated DTG-based vs. other guideline recommended regimens in clinical care across the United States. Methods PLWH from eight CFAR Network of Integrated Clinical Systems (CNICS) sites who started a recommended regimen between August 2013 and August 2016 were included. We compared DTG vs. other INSTI, and vs. darunavir-based (DRV) regimens included in current guidelines for initiating antiretroviral therapy (ART). VF was defined as a viral load of >400 copies/ml >6 months after initiation. We used Cox models adjusting for age, sex, race/ethnicity, hepatitis B, hepatitis C, tuberculosis, HIV risk factor, CD4 count, days since last HIV viral load, and site. PLWH were censored at death, regimen change or loss to follow-up (LTFU) with sensitivity analyses varying LTFU definitions from 0 to 12 months after last activity and including/excluding inverse probability censoring weights based on variables in the main models. Results Among 6636 PLWH who initiated a recommended regimen, a lower proportion on DTG-based regimens experienced VF during follow-up (Figure). The adjusted hazard ratio (HR) for VF for DTG vs. DRV-based regimens was 0.56 (95% confidence interval 0.37–0.86). In sensitivity models, the HR for VF for DTG vs. other INSTI regimens ranged from 0.73 to 1.07 depending on LTFU definitions. The HR for DTG vs. DRV-based regimens ranged from 0.38 to 0.63 depending on LTFU definitions. In sensitivity analyses among the 1,229 PLWH known to be ART-naive at initiation, a similar pattern was found with a lower HR of VF among those who initiated DTG vs. DRV-based regimens (HR 0.25, 95% CI 0.11–0.56). Conclusion The observed rate of VF during follow-up was lower among PLWH initiating DTG-based vs. DRV-based regimens in routine clinical care at sites across the US. Results also demonstrated that different definitions of LTFU can have a large impact on the results and highlight the importance of sensitivity analyses in informing study definitions to minimize bias. Disclosures V. Vannappagari, ViiV Healthcare: Employee and Shareholder, Salary and Stocks; K. Smith, ViiV Healthcare: Employee, Salary; C. Johannes, VIIV: Research Contractor, Research support; B. Calingaert, VIIV: Research Contractor, Research support; C. Saltus, VIIV: Research Contractor, Research grant; J. Eron, VIIV: Scientific Advisor, Consulting fee; M. S. Saag, VIIV: Grant Investigator and Scientific Advisor, Grant recipient; BMS: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient; Gilead: Grant Investigator and Scientific Advisor, Consulting fee and Research support; Merck: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient; H. M. Crane, VIIV: Scientific Advisor, Nothing to date but I have been asked to be an advisor so there may be a relationship in the future.

scholarly journals Sword 1 and 2: Subgroup Analysis of 48 Week Results by Age, Race and Gender

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S427-S427 ◽  
Author(s):  
Sharon Walmsley ◽  
Gary Richmond ◽  
Fritz Bredeek ◽  
Moti Ramgopal ◽  
Chien-Ching Hung ◽  
...  
Keyword(s):  
Board Member ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Research Support ◽  
Once Daily ◽  
Race And Gender ◽  
Grant Recipient ◽  
And Gender ◽  
Hiv 1 ◽  
Research Grant

Abstract Background Switching to the 2-drug regimen (2DR) of DTG+RPV was proven non-inferior to continuing a suppressive PI-, INI- or NNRTI- based current antiretroviral regimen (CAR) at Week 48. This analysis evaluated the efficacy and safety of switching from CAR to DTG+RPV by age, race and gender subgroups. Methods Two identically designed, open-label, multicenter, global, phase III, non-inferiority studies compared the efficacy and safety of switching from a 3 or 4-drug CAR to DTG + RPV once daily in HIV-1-infected adults, with HIV-1 RNA<50 c/mL. Primary endpoint was proportion of patients with VL<50 c/mL at Wk48 using FDA Snapshot. Additional analysis were performed to summarize efficacy base on age, race and gender subgroups for each individual study and pooled. Results 1024 patients were randomized and exposed (DTG+RPV 513; CAR 511), across both studies. Treatment arms were well matched for demographic and baseline characteristics. Median age across both arms was 43.4 years, with 29% and 28% ≥ 50 years in DTG+RPV and CAR, respectively. 23% and 21% were female while 18% and 22% were non-white for DTG+RPV and CAR. For the pooled studies and for SWORD-1 and SWORD-2 individually, switching to DTG+RPV was non-inferior to CAR at Wk48. Similar response rates were observed in the DTG+RPV arm compared with CAR across subgroups (Table 1). More AEs were reported in the DTG+/RPV arm across all subgroups except Asian race; no unexpected AEs were identified for either drug. Conclusion Switch to a novel, once daily 2DR of DTG+RPV in patients with a suppressed viral load, was an effective and well tolerated treatment option across age, race, and gender subgroups which were consistent with overall results. Disclosures S. Walmsley, Merck: Board Member, Consultant, Grant Investigator, Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Grant recipient, Research grant and Speaker honorarium; ViiV Healthcare: Board Member, Consultant, Grant Investigator, Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Grant recipient, Research grant and Speaker honorarium; Gilead Sciences: Board Member, Consultant, Grant Investigator, Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Grant recipient, Research grant and Speaker honorarium; GSK: Board Member, Consultant, Grant Investigator, Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Grant recipient, Research grant and Speaker honorarium; Janssen: Board Member, Consultant, Grant Investigator, Investigator, Scientific Advisor and Speaker’s Bureau, Grant recipient, Research grant and Speaker honorarium; BMS: Grant Investigator, Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Grant recipient, Research grant and Speaker honorarium; G. Richmond, Viiv Healthcare: Investigator, Research support; 
 F. Bredeek, ViiV Healthcare: Investigator and Scientific Advisor, Consulting fee and Research support; M. Ramgopal, viiv: Investigator, Consulting fee; C. C. Hung, Gilead Sciences: Board Member and Speaker’s Bureau, Consulting fee and Speaker honorarium; ViiV: Board Member and Investigator, Consulting fee and Research support; Abbvie: Board Member and Investigator, Consulting fee and Research grant; Bristol-Myers Squibb: Investigator, Research support; Jassen: Board Member and Investigator, Consulting fee and Research support; E. Blair, ViiV Healthcare: Employee and Shareholder, Salary; L. Kahl, ViiV Healthcare: Employee and Shareholder, Salary; M. Underwood, ViiV Healthcare: Employee, Salary; K. Angelis, GlaxoSmithKline: Employee, Salary; K. Vandermeulen, Jansen: Employee, Salary; B. Wynne, ViiV Healthcare: Employee, Salary; M. Aboud, ViiV Healthcare: Employee, Salary

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