bluuebunny/crossref_metadata_2025_split huggingface dataset:
2482. Clinical Outcomes of Once-Daily Darunavir in Treatment-Experienced Patients with Darunavir Resistance Associated Mutations Through 48 Weeks of Treatment
Authors: Rolle Charlotte-Paige M , Marquez Omar , Nguyen Vu , Hinestrosa Federico , DeJesus Edwin 
Published: October 2019

Abstract

Background
Darunavir (DRV) is a well-tolerated, potent protease inhibitor used once-daily in patients with no DRV resistance-associated mutations (RAMs) and twice-daily in those with DRV RAMs. Treatment guidelines encourage use of once-daily regimens to optimize patient adherence, convenience and tolerability. Several studies suggest that once-daily DRV retains efficacy in the setting of 1–2 DRV RAMs whereas 3 or more DRV RAMs (with multiple background PI RAMs) is needed for DRV resistance. Currently, there is little clinical data to support the long-term use of once-daily DRV in patients with DRV RAMs.

Methods
This is a retrospective study evaluating the 48-week clinical outcomes of 22 treatment-experienced patients with DRV RAMs switched to once-daily DRV between 2014 and 2017 at the Orlando Immunology Center. The primary endpoint was the proportion with virologic suppression (HIV-1 RNA< 50 copies/mL) at Week 48. Adherence, adverse events (AEs) and laboratory parameters were analyzed throughout the study.

Results
The median age (range) of the sample was 53 (21–77) years, median baseline CD4+ count was 609 cells/mm3, 18 (82%) had baseline HIV-1 RNA <50 copies/mL, 15 (69%) had previously used 1 or more PIs and median number (range) of baseline DRV RAMs was 2 (1–5) (Table 1). At Week 48, 20 (91%) had HIV-1 RNA <50 copies/mL; 2 (9%) virologic non-responders had HIV-1 RNA of 82 and 59,637 copies/mL and reported noncompliance (Figure 1). There was no significant change in median CD4+ count from baseline to Week 48 (+22, 95% confidence interval (CI): [−116.5; 56.0]). Once-daily DRV was associated with a significant median increase in HDL cholesterol (+82, 95% CI: [37.0; 101.0]) and a significant median decrease in LDL cholesterol (-60, 95% CI: [-89.5; -31.0]). There were no significant changes in the proportion of patients on lipid lowering therapy at baseline and week 48 (p = 0.33). There were no self-reported AEs or Grade 3–4 lab abnormalities through Week 48.

Conclusion
Once-daily DRV maintained virologic control in this cohort of treatment-experienced patients with 1 or more baseline DRV RAMs and was safe and well-tolerated. This suggests that once-daily DRV may be effective in this population however further data are needed to validate this as a viable treatment option.

Disclosures
All authors: No reported disclosures.
2489. Adverse Events with Biktarvy: Post-Marketing Study
Authors: Hayes Edwin , Derrick Caroline , Smalls Danielle , Smith Hilary , Kremer Nicole , Weissman Sharon 
Published: October 2019

Abstract

Background
Bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) was FDA approved in February 2018. There are no published post-marketing data evaluating safety and efficacy. After large uptake of BIC/FTC/TAF at our institution, reports of rash prompted a real-world review. The purpose of this study was to assess one year post-marketing safety and tolerability of BIC/FTC/TAF.

Methods
This retrospective, observational, pharmacoepidemiologic study was conducted one year post-approval of BIC/FTC/TAF, between February 2018 and March 2019 at the University of South Carolina Immunology Center. Adults receiving BIC/FTC/TAF were included. Drug discontinuation and treatment-related adverse effects were evaluated. Baseline demographics and serial laboratory data were collected.

Results
A total of 201 patients were assessed. Of those, the majority were treatment experienced (181, 90%), African American (137, 68%) males (132, 65%) with a mean age of 46 years (range 20–76 years). Four patients were transgender. 135 (67%) had a BMI of ≥ 25 kg/m2 and 77 (38%) had a BMI of ≥ 30 kg/m2. At baseline, 146 (72.6%) had virologic suppression (VS) (< 200 copies/mL) with a mean CD4 count of 529 cells/mm3 (range < 35–1573 cells/mm3). VS was maintained in 145/146 and subsequently reached in 47/55 (85.5%) at first follow-up. Of the 201, 18 (8.9%) patients reported adverse drug events (ADEs) for a total of 19 events (10 rash, 2 dizziness, 1 nausea/vomiting, 1 headache, 1 diarrhea, 1 loss of appetite, 1 weight gain, 1 fatigue, 1 insomnia). Eleven (5%) patients discontinued therapy; nine (4%) due to ADEs (7 rash, 1 insomnia and loss of appetite, and 1 feeling unwell). One patient with high AST/ALT at baseline increased from 129/243 U/L to 234/394 U/L, respectively. No other laboratory abnormalities were reported.

Conclusion
In a southern, predominantly African American overweight population, our results demonstrate low discontinuation rates associated with BIC/FTC/TAF, with rash being the predominate cause. Overall, 4% discontinued BIC/FTC/TAF due to ADEs compared with 1% as reported in the package insert. VS rates were high throughout the evaluation period. Ongoing post-marketing evaluation is important for early recognition of unexpected adverse outcomes.

Disclosures
All authors: No reported disclosures.
2512. Decreasing Adherence to Antiretroviral Therapy over 4 Years of Follow-up in a Commercially-Insured Population of Patients with HIV
Authors: Priest Julie , Bhak Rachel , DerSarkissian Maral , Garris Cindy , Oglesby Alan , Kunzweiler Colin , Fuqua Ellie , Park Suna , Sheng Duh Mei 
Published: October 2019

Abstract

Background
This study compared yearly and longer term antiretroviral (ARV) adherence among HIV patients overall and by single-tablet regimens (STRs) vs. multi-tablet regimens (MTRs).

Methods
A retrospective study using Optum Clinformatics US-based claims data was conducted. Patients with an HIV-1 diagnosis during 2011–2017, age ≥ 18 years at index (date of first complete ARV regimen during the study period), and continuous enrollment for ≥ 3 months before index (baseline) and ≥ 12 months after index (observation) were included. MTRs were required to be comprised of 3 or more agents across at least 2 classes. Adherence was measured as the proportion of days covered (PDC) and compared using a Chi-square test. PDC was examined in the 1-year observation period for the overall analysis, and each year following index among patients with at least 4 years of continuous data. A subgroup analysis was conducted among patients with index during 2014–2016 to evaluate modern ARV adherence.

Results
Among the 15,153 included patients, median age was 45 years, the majority were male (88%), and 53% were in the South. At baseline, 58% (n = 8,715) were receiving an STR and 43% (n = 6,438) an MTR. Compared with STR patients, MTR patients had higher prevalence of hyperlipidemia (36% vs. 29%), cardiovascular disease (27% vs. 21%), and hypertension (25% vs. 20%). During year 1, the proportion of patients with PDC ≥ 0.90 was 63% overall (Table 1), and greater for STR than MTR (67% vs. 58%, P < .001). Among patients with at least 4 years of observation, PDC ≥ 0.90 decreased over time (from 67% in year 1 to 53% in year 4). In the subgroup of patients with index during 2014–2016 (Table 2), similar but slightly worse trends were observed, with PDC ≥ 0.90 for 57% of patients overall, and decreasing over time for those patients with at least 3 years of observation (59% in year 1 to 42% in year 3).

Conclusion
Adherence in this population of patients with HIV showed room for improvement in the first year of observation overall and in the modern ARV era, with those receiving STRs having higher adherence when compared with those receiving MTRs. For the patients with 4 years of follow-up, adherence tended to decrease year on year. Maintaining high rates of ARV adherence is a critically important aspect of therapy for patients with HIV.

Disclosures
All authors: No reported disclosures.
2516. Persistence of Anti-HIV Antibodies in HIV-1-infected Patients on Combination Antiretroviral Therapy (cART) with Prolonged Viral Suppression
Authors: Singh Kanal , Davis Ivery , Dewar Robin L , Imamichi Hiromi , Lane H Clifford 
Published: October 2019

Abstract

Background
Despite years of cART with sustained HIV-RNA plasma viral load (pVL) < 50 copies/mL, antibodies (Abs) to HIV-1 proteins persist. The reasons for this are unknown but may reflect long-lived B cell responses and/or persistence of antigen. To address which of these may be the case, we compared decay rates of anti-HIV Abs to those of anti-Measles Abs.

Methods
A cohort of 10 HIV-infected patients on cART with pVL < 50 (average 3 years, range 0–7.1 years) were studied. Baseline and 5-year follow-up serum were collected and assessed for anti-HIV-1 Abs via western blot (Cambridge Biotech WB kit), with additional densiometric analysis used for quantitative calculation of a western blot “score” that was normalized to control specimens. The kinetics of measles Abs titers over the same 5-year period were also analyzed by the quantitative Serion Measles IgG ELISA kit, given a history of prior vaccination in these participants. McNemar’s and paired t-tests were used for analysis.

Results
All 10 patients exhibited persistence of anti-HIV-1 Abs at ≥ 5 year follow-up as determined by persistence of ≥ 2 diagnostic bands on WB (P = 0.003). The patterns for all 10 participants varied individually by patient with each exhibiting a unique profile (representative figure); 7/10 patients had WBs that could be analyzed quantitatively and showed no significant change over the study period (average baseline score 5.9 vs 5.3 at follow-up, P = 0.26). 7/9 patients had valid measles IgG measurements showing a consistent but nonsignificant decline over the same 5-year study period (measles titer 55–2800 mIU/mL at baseline vs 50–1300 mIU/mL at follow-up, n = 9, P = 0.18).

Conclusion
The mechanism leading to the persistence of anti-HIV-1 Abs in HIV-infected individuals with prolonged viral suppression has been unclear. The general decline in anti-Measles IgG titer over the 5-year observational period in 7/9 patients is likely to be explained by waning B cell-mediated humoral immunity in these vaccinated individuals and consistent with their lack of ongoing exposure to this pathogen. The persistence of anti-HIV-1 Abs over the same 5-year period, on the other hand, may indicate persistent HIV-1 viral protein production either from active reservoirs or by transcription of “defective” HIV-1 proviruses as recently reported.

Disclosures
All authors: No reported disclosures.
2520. Resource utilization in adolescents and young adults with HIV in the HIV Research Network
Authors: Neilan Anne M , Lu Frances , Gebo Kelly , Diaz-Reyez Rebeca , Huang Mingshu , Parker Robert , Karalius Brad , Patel Kunjal , Voss Cindy , Ciaranello Andrea , Agwu Allison 
Published: October 2019

Abstract

Background
Adolescents and young adults (AYA) with HIV experience worse health outcomes than adults with HIV in the United States. Little is known about AYA patterns of utilization of costly healthcare resources.

Methods
We estimated utilization of outpatient, emergency department (ED), and inpatient care among 13–30 year-olds from 2006–2015. We stratified outpatient visits, ED visits and inpatient days per person-year (PY) by transmission mode (perinatal (PHIVY), non-perinatal (NPHIVY), age (13–17, 18–23, 24–30 years), CD4 strata (< 200, 200–499, ≥ 500 cells/µL) and presence or absence of viral load (VL) suppression (<, ≥ 400 copies/mL[c/mL]) combined with antiretroviral (ARV) use. We also quantified outpatient, ED, and inpatient care associated with specific AIDS-defining conditions.

Results
Among 4,450 AYA (PHIVY: 15%; NPHIVY: 85%), mean (SD) follow-up was 2.8 years (2.5) [PHIVY: 4.2 years (3.1); NPHIVY: 2.5 years (2.3)]. Mean age was 21.4 years (PHIVY: 16.9 years; NPHIVY: 22.3 years) and female sex was 28% (PHIVY: 52%; NPHIVY: 23%). Among PHIVY, most person-time (PT) was spent between ages 13–23 years (13–17 years: 43%; 18–23 years: 45%), CD4 ≥ 500/µL (61%), and VL < 400 c/mL (69%). Among NPHIVY, most PT was spent between ages 24 and 30 years (56%), CD4 ≥ 500/µL (54%), and VL < 400 c/mL (66%). PT spent while prescribed ARVs and VL ≥ 400 c/mL was 30% (PHIVY) and 24% (NPHIVY). For both PHIVY and NPHIVY, outpatient visit rates were higher at younger ages (13–17 years and 18–23 years), lower CD4 (< 200, 200–499/µL), and among those prescribed ARVs (Figure 1). Rates of ED visits and inpatient days were higher during PT spent at older ages (18–23 years, 24–30 years), lower CD4 (< 200, 200–499/µL), and VL ≥ 400 c/mL (Figures 2 and 3). Overall, utilization was higher among PHIVY than NPHIVY (outpatient: 12.1 vs. 6.0/PY; ED: 0.4 vs. 0.3/PY; inpatient: 1.5 vs. 0.8/PY). The overall rate of AIDS-defining conditions was 4.5/100 PY (Figure 4).

Conclusion
Among AYA with HIV, more ED visits and inpatient days were observed during time spent at older ages, lower CD4 counts, and VL ≥ 400 c/mL. While AIDS-defining conditions were rare, associated resource utilization was substantial. Interventions to improve retention in care, virologic suppression, and immune response may improve outcomes, and thus decrease costly resource utilization, for AYA with HIV as they transition to adulthood.

Disclosures
All authors: No reported disclosures.
2545. Needs Assessment for a Presentation Skills Curriculum in an Infectious Diseases Fellowship Program
Authors: Bares Sara H , Van Schooneveld Trevor C , Marcelin Jasmine R , Marcelin Jasmine R , Nada Fadul , Zimmer Andrea 
Published: October 2019

Abstract

Background
Presentation skills are critical for infectious diseases fellows regardless of their ultimate career path. Despite this, there is little emphasis on training in presentation skills within the infectious diseases (ID) fellowship curricula.

Methods
To determine the perceived need for a presentation skills curriculum for ID fellows, faculty and fellows were asked to complete a brief online needs assessment. The survey included questions on demographics, prior presentation experience and skills training, perceived need for and interest in a presentation skills curriculum, and the preferred modality for such a curriculum. Descriptive statistics were calculated for each theme.

Results
In April 2019, 4/4 fellows and 15/22 faculty members completed the online survey. While all fellows (100%) agreed or strongly agreed their presentation skills could be improved, only 50% wanted more feedback about their presentation skills and only 50% were interested in training to improve their presentation skills (Figure 1). Concerns about time constraints were noted in the optional comments. Most faculty (87%) agreed or strongly agreed that fellow presentation skills could be improved and most felt empowered (73%) and were willing (73%) to provide the fellows with feedback. Only 27% of faculty reported prior training in presentation skills and 60% expressed an interest in receiving training before providing the fellows with feedback. Regarding presentation skills feedback modalities (Figure 2), fellow respondents expressed a preference for written feedback (75%) and in-person, one-on-one feedback (75%); faculty respondents were willing to provide written feedback (93%), in-person, one-on-one feedback (80%) and in-person feedback with a group of other faculty (73%).

Conclusion
This study provides a framework for ID fellowship programs interested in developing a presentation skills curriculum. The results support the need for a presentation skills curriculum, but interest in such a curriculum is not universal. Our findings will guide the development and structure of a curriculum that will target interested faculty and aim to benefit the fellows without putting an undue onus on their time and other commitments.

Disclosures
All authors: No reported disclosures.
2577. Periodontal Disease and the Oral Microbiome in Alcohol-Dependent Individuals
Authors: Meeks Brianna K , Barb Jen , Mudra Sarah E , Kazmi Narjis , Tuason, Ralph T S , Schuebel Kornel , Brooks Alyssa T , Krumlauf Michael , Brenchley Laurie , Gardner Pamela J , Goldman David , Wallen Gwenyth R , Ames Nancy J 
Published: October 2019

Abstract

Background
Periodontal disease results from a polymicrobial infection composed of pathogenic bacteria that colonize the oral cavity, resulting in loss of periodontal attachment and alveolar bone. Periodontitis can increase the risk or exacerbate other comorbidities. Alcohol use increases the risk of periodontitis, but there is little knowledge about periodontitis among people who misuse alcohol.

Methods
As part of a larger oral and gut microbiome study, this analysis examines the oral microbiome in the occurrence and severity of periodontitis among alcohol-dependent (AD) subjects undergoing a 28-day inpatient alcohol treatment program. Tongue brushings were collected from 22 subjects within the first week of admission, and 16S rDNA sequencing was performed. All subjects had a dental examination during the inpatient stay. This analysis divided periodontal disease status into three major groups–no disease, mild or moderate disease, and severe disease. One-way ANOVA was used to compare microbial genera across the 3 groups.

Results
Nineteen (86%) of the subjects had periodontitis: 16 had mild or moderate disease, and 3 had severe disease. Statistically different microbial genera in at least one of the three groups (P ≤ 0.05 corresponding to FDR ≤ 0.25) that had a relative abundance of at least 0.5% include: Bifidobacterium, Lactobacillus, Parvimonas, Peptostreptococcus, Porphyromonas, and Treponema. Surprisingly, the subjects with no periodontitis had increased abundances of genera that are often pathogens, Porphyromonas and Peptostreptococcus. Subjects with severe periodontitis had increased abundances of known pathogens Treponema and Parvimonas, as well as Lactobacillus, which has been associated with dental caries.

Conclusion
We observed that periodontitis accompanies chronic AD, given that 86% of our subjects had the disease. While some microbiome differences for individuals with and without periodontitis were not consistent with the existing literature, this may have many explanations. Future studies should consider how chronic AD could change the microbial ecology of the mouth and lead to further infection as well as utilizing multiple oral sites and a larger sample size to better understand the relationship between AD and periodontal disease.
Intramural funds from NIH

Disclosures
All authors: No reported disclosures.
2579. Impact on the Gut Microbiota of the Prolonged Antimicrobial Therapy in Patients with Bone and Joint Infection (BJI): Results From the OSIRIS Prospective Study in France
Authors: Levast Benoit , Batailler Cécile , Pouderoux Cécile , Boucihna Lilia , Lustig Sébastien , Boutoille David , Dauchy Frederic-Antoin , Zeller Valérie , Senneville Eric , Maynard Marianne , Laurent Frederic , Ferry Tristan 
Published: October 2019

Abstract

Background
There is growing interest about the deleterious impact of antibiotics on loss of gut symbiosis, called dysbiosis. As patients with BJI require antibiotics usually during 6 to 12 weeks, it is of interest to determine whether dysbiosis is frequent in this population, and if it could potentially reversible or not.

Methods
Multicentric prospective cohort study in France (EudraCT 2016-003247-10) including patients with 3 categories of BJI: native, osteosynthesis-related and prosthetic joint infection (PJI). At the time of suspicion (V1), at the end of therapy (V2) and then 2 weeks after stopping therapy (V3), blood and fecal samples were collected. Extracted DNA from stool was sequenced using shotgun metagenomic sequencing based on illumina library and Iseq instrumentation. Data run through a dedicated pipeline in order to produce microbiome indexes such as Sympson or Shannon diversities indexes. Gut microbiome and inflammation markers were analyzed including fecal neopterin, a maker of gut inflammation.

Results
Concerning the 62 patients included (mean age, 60 years; mean duration of antibiotics, 66 days), 27 had native, 14 had osteosynthesis and 21 had PJI. The most frequently prescribed drug was a fluoroquinolone, followed by a third-generation cephalosporin and vancomycin. Stools from 42 of them were analyzed as per protocol. Overall, the mean Shannon richness index decreased from 0.904 at V1 to 0.845 at V2; the Bray-Curtis index underlined the difference in microbiome reconstitution at V3 in comparison with V1. We report significant microbiome loss of diversity at V2, that was reversible at V3 in patients with native BJI and osteosynthesis-related BJI, but not in patients with PJI (figure). Fecal neopterin increased between V1 and V2 (mean 221.6 and 698.1 pmol/g of feces, respectively) and then decreased at V3 (422.5 pmol/g), and could be a potential surrogate marker of gut dysbiosis. Of note, patients with abnormal CRP at the end of antibiotics had high neopterin values, that raises the hypothesis that abnormal CRP at the end of antibiotics could be in relation with gut dysbiosis rather than uncured BJI.

Conclusion
The impact of antibiotics on the gut microbiota of patients with BJI seems to be significant, especially in patients with PJI who could be candidate for fecal microbiota transplantation.

Disclosures
All authors: No reported disclosures.
2580. Serial Microbiome Analysis in a Patient with Multiple Failed Fecal Microbiome Transplantations
Authors: Gonzales-Luna Anne J , Lancaster Chris , Khan M A Wadud , Begum Khurshida , Endres Bradley T , Rashid Tasnuva , Carlson Travis J , Alam M Jahangir , Garey Kevin W 
Published: October 2019

Abstract

Background
Fecal microbiota transplantation (FMT) is recommended to treat refractory or recurrent cases of Clostridioides difficile infection (CDI) through restoration of a healthy intestinal microbiome. The procedure has reported success rates of 90% or higher for CDI, but several risk factors for FMT failure have been identified. Here we present a case of a patient failing four FMT procedures over a 2-year period, with accompanying microbiome and metagenomic analyses.

Methods
Seven serial C. difficile-positive stool samples were collected as part of an ongoing surveillance system in Texas. Samples, including the index case, represented independent CDI episodes interspersed between four separate FMT procedures between 2016 and 2018. PCR ribotype (RT) testing, 16S rRNA gene sequencing, MIC testing, multidrug-resistant organism (MDRO) screening, and shotgun metagenome sequencing were conducted for each of the samples.

Results
The patient was a 42-year-old female with various comorbidities, including systemic lupus erythematosus. She received continuous non-CDI antibiotic courses throughout her CDI therapy for a variety of infections. The vancomycin MICs in infecting C. difficile strains increased with cumulative vancomycin exposure. Multidrug-resistant organisms were detected in stool, including Enterococcus spp., MRSA, and Candida glabrata. The first five of the seven strains were RT 078–126, one was mixed RT 002 and RT 054, and one was RT 002. The analysis of 16S rRNA gene sequences demonstrated that microbial diversity was never restored after FMT procedures. A strong correlation between microbial and functional gene compositions suggests that fecal samples share many microbial species with associated functional genes.

Conclusion
A number of systems biology changes were observed in a patient with persistent CDI despite multiple FMTs. The lack of FMT engraftment was most likely due to continuous broad-spectrum antibiotic exposure in an immunocompromised patient.

Disclosures
All authors: No reported disclosures.