bluuebunny/crossref_metadata_2025 huggingface dataset:
1011. Efficacy and Safety of Doravirine in Treatment-Naïve Adults ≥50 Years Old With HIV-1
Authors: Mills Anthony , Martin Elizabeth A , Liu Chih-Chin , Drolet Martine , Sklar Peter
Published: January 2021

Background

Nearly 50% of people living with HIV in the US are ≥50 years old. Older people are more likely to have late-stage HIV infection at diagnosis, greater risk for cardiovascular disease and certain cancers, and concurrent medications for common age-related conditions. Doravirine (DOR) is a next-generation NNRTI with activity against first-generation NNRTI-associated mutations, a neutral impact on lipids, and few drug-drug interactions with commonly used medications.

Methods

We compared Week 96 results from DOR Phase 2 and Phase 3 trials (P007, P018, and P021) in treatment-naïve adults ≥50 vs < 50 years old. 855 participants received DOR 100mg +2 NRTIs in P007 & P018 or fixed combination DOR/3TC/TDF in P021; 383 participants received ritonavir-boosted darunavir (DRV) +2 NRTIs in P018; and 472 received efavirenz (EFV) 600mg +FTC/TDF in P007 or fixed combination EFV/FTC/TDF in P021. Participants who took ≥1 dose of study drug were included; the Observed Failure approach was used for missing efficacy data. All analyses were done by descriptive statistics.

Results

Of 1710 participants, 187 (11%) were 50-70 (median 54) years old at study entry. Baseline characteristics and treatment outcomes are summarized below for participants < 50 vs ≥50 years old. The older cohort had more women, more participants with AIDS, and lower median CD4+ T-cell counts than the younger cohort, whereas baseline HIV-1 RNA was similar between age cohorts. Hypertension and use of analgesics were more common in older participants. In each treatment group, the older cohort had a higher proportion of participants with HIV-1 RNA< 50 copies/mL at week 96 and fewer discontinuations due to lack of efficacy than the younger cohort. Mean change in CD4+ T-cell count was similar between age cohorts in the DOR and DRV groups and was lower for older participants in the EFV group. Rates of drug-related AEs and serious drug-related AEs were similar between age cohorts across all treatment groups. Discontinuations due to drug-related AEs were similar between age cohorts in the DOR group and were slightly higher for older participants in the DRV and EFV groups.

Conclusion

DOR is a beneficial option for adults ≥50 years old, given its similar efficacy and favorable safety profile compared to younger adults.

Doravirine Phase 2 and Phase 3 Trials in Treatment-Naïve Adults

Disclosures

Anthony Mills, MD, Gilead (Grant/Research Support, Advisor or Review Panel member)Janssen Pharmaceutica (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Shionogi (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Advisor or Review Panel member) Elizabeth A. Martin, DO, MPH, MBA, Merck & Co., Inc. (Employee) Chih-Chin Liu, PhD, Merck & Co., Inc. (Employee) Martine Drolet, BPharm, LPH, MBA, Merck & Co., Inc. (Employee) Peter Sklar, MD, MPH, Merck & Co., Inc. (Employee)
1018. Health Technology Assessment of New Long-Acting, Directly-Observed HIV Treatments in Canada: Impact of Real-World Adherence to Daily Oral Therapy on Treatment, Transmission and Cost-Effectiveness
Authors: Arthurs Erin , Parker Ben , Jacob Ian , Becker Debbie , Lee Amy , Hayward Olivia , Chounta Vasiliki , Anderson Sarah-Jane , Van de Velde Nicolas
Published: January 2021

Background

Current antiretroviral therapy (ART) has dramatically improved outcomes for people living with HIV (PLWHIV), however adherence to daily oral dosing remains a challenge for some. New, long-acting (LA) ARTs which are directly administered by physicians eliminate the need to adhere to daily oral dosing and may improve clinical outcomes. The study objective was to evaluate costs and QALYs associated with improved adherence achieved via a novel, directly-observed therapy (DOT) of a monthly LA injectable ART, compared to standard of care (SoC), daily oral therapy.

Methods

A published Markov cohort state-transition model was adapted to model the impact of treatment adherence and subsequent disease transmission. Without the need to adhere to daily dosing, the efficacy of the injectable was modelled independent of adherence whereas virologic suppression in the SoC arm was adjusted to reflect published data on adherence to daily dosing (8.12% below optimal levels observed in clinical trials).

Results

This evidence-based approach of accounting for adherence revealed an increase in lifetime costs for oral SOC of approximately $850, and QALY loss of 0.109 when compared to results without accounting for adherence. Disease transmission results yielded 3 cases averted of HIV per 1,000 patients with LA’s impact on adherence.

Conclusion

In the absence of comparative adherence estimates between a LA, injectable DOT and daily oral therapy in the real world, an evidence-based approach provides a method to address the uncertainty around the true impact on costs and QALYs of a novel mode of administration.

Disclosures

Erin Arthurs, MSc, GlaxoSmithKline (Employee) Ben Parker, MSc, HEOR Ltd. (Employee) Ian Jacob, MSc, HEOR Ltd (Employee) Debbie Becker, MSc, GSK (Consultant) Amy Lee, MSc, PhD, GSK (Consultant) Olivia Hayward, PhD, HEOR ltd. (Employee) Vasiliki Chounta, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Sarah-Jane Anderson, PhD, GlaxoSmithKline (Employee, Shareholder) Nicolas Van de Velde, PhD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)
1020. Higher efavirenz mid-dose plasma concentration is associated with less weight gain among virologically suppressed people living with HIV
Authors: Huang Wei-chieh , Huang Sung-Hsi , Hung Chien-Ching
Published: January 2021

Background

Recently, an association between CYP2B6 516 G > T polymorphism and weight change was observed among African people living with HIV (PLWH) who were started on efavirenz(EFV)-based antiretroviral therapy (ART). We aimed to investigate the effect of EFV mid-dose plasma concentration on weight change among Taiwanese PLWH.

Methods

The medical records of adult PLWH who were taking EFV-containing ART and had been enrolled in a EFV therapeutic drug monitoring study between Oct 2009 and May 2014 were accessed. EFV mid-dose plasma concentration (C12) was determined in the previous study and those with serial weight measurements within 48 weeks around the time of EFV C12 measurement were included in the present study. The weight change in the 48 weeks and its associations with mid-dose EFV concentrations and CYP2B6 516 G > T polymorphism were examined by general estimating equations (GEE) after adjusting for age, baseline HIV viremia, baseline weight, and the companion backbone antiretroviral agents.

Results

One-hundred and fifteen predominantly male (94.8%) PLWH were included in this study (Table 1). The mean CD4 lymphocyte count was 542 cells/μL at the beginning of the observation and 94.8% achieved HIV viral suppression. Forty-four (38.3%) patients had non-wildtype CYP2B6 516 G > T polymorphism. On average, the included PLWH gained 0.8 kilogram at 48 weeks and the weight change did not differ among those with wildtype and non-wildtype CYP2B6 516 G > T(Figure 1). In the GEE models, CYP2B6 516 G > T polymorphism was not associated with weight change (p=0.81), instead, higher EFV C12 was found to be independently associated with less weight gain (p=0.045).

Table 1. Baseline characteristics.

Figure 1. The absolute weight (A) and weight change from baseline (B) among patients with wildtype and non-wildtype CYP2B6 516G>T polymorphism.

Conclusion

Our findings support that increased EFV exposure may have a negative effect on weight gain.

Disclosures

Chien-Ching Hung, MD,PHD, Abbvie (Advisor or Review Panel member, Speaker’s Bureau)Bristol-Myers Squibb (Speaker’s Bureau)Gilead Sciences (Advisor or Review Panel member, Speaker’s Bureau)Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support)ViiV (Grant/Research Support, Advisor or Review Panel member, Speaker’s Bureau)
78. Outcomes and adherence to institutional empiric therapy guidelines for the treatment of cystitis in ambulatory male veterans
Authors: Pham Selena N , Ashong Chester , Rodriguez-Barradas Maria C , Hunter Andrew
Published: January 2021

Background

Guidelines provide primary literature demonstrating efficacy and safety of cystitis treatment in female patients, but not males. Increased antimicrobial resistance of urinary tract infection (UTI) pathogens to first line antibiotics are well-documented. In 2017, a change in institutional guidelines was made to recommend nitrofurantoin (NF) or cefpodoxime (CPD) as first line antibiotics for cystitis in males. This study aims to evaluate the efficacy of NF and CPD as first line treatment options in males with cystitis.

Methods

Single-center, retrospective chart review of male patients prescribed NF or CPD for treatment of cystitis in the outpatient setting from August 2017 to August 2018. Patients with asymptomatic bacteriuria, prostatitis or systemic signs and symptoms of UTI were excluded. Primary outcome was treatment failure, defined as requiring new emergency department (ED) or patient aligned care team (PACT) visit within 30 days after initiation of antibiotic for unresolved symptoms. Safety outcomes were based on documented adverse effects (AE) associated with antibiotic use. Chi-square was the primary statistical test for analyzing primary outcomes and other nominal variables.

Results

A total of 450 charts were reviewed with 150 patients meeting inclusion criteria (NF n = 75, CPD n = 75). Baseline characteristics were equally distributed between the two groups although the CPD group had higher serum creatinine compared to the NF group (p = 0.05). Nine patients (12%) in the NF group versus 13 patients (17.3%) in the CPD group returned to ED or PACT within 30 days (p=0.36). Inappropriate dosing was seen in 13 patients (17.3%) in the NF group vs. 2 patients (2.7%) in the CPD group (p = 0.005) and 44 patients (58.7%) in the NF group vs. 37 patients (49.3%) in the CPD group who received an inappropriate duration of treatment (p = 0.25). None of the patients reported AE associated with antibiotic use.

Conclusion

Treatment success rate of NF and CPD (88% and 82.7%, respectively) suggests that these agents might be effective first line antibiotics for cystitis in males. High rate of inappropriate long duration of treatment indicates the need for staff education and prospective audit and feedback for outpatient stewardship interventions.

Disclosures

All Authors: No reported disclosures
1044. The Incidence and Severity of Drug interactions Before and After Switching Antiretroviral Therapy to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Treatment Experienced Patients
Authors: Schafer Jason J , Pandit Neha S , Cha Agnes , Huesgen Emily , Badowski Melissa E , Sherman Elizabeth , Cocohoba Jennifer , Shimada Ayako , Keith Scott
Published: January 2021

Background

Switching antiretroviral therapy (ART) in virally suppressed people with HIV (PWH) can simplify treatment, improve tolerability, and limit long-term toxicity. It can also influence the presence of drug interactions (DIs) in a positive or negative manner among patients receiving concomitant medications (CMs). The extent to which switching ART to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) influences DIs in treatment-experienced PWH is unclear. The purpose of this study was to assess changes in the incidence and severity of DIs after switching to BIC/FTC/TAF.

Methods

This was a multicenter retrospective cohort study of PWH on ART and at least one prescription CM who switched to BIC/FTC/TAF between 3/2018 and 6/2019. Using the University of Liverpool’s HIV drug interaction checker, two DI analyses were performed for each patient. The first assessed patients’ pre-switch ART regimen with their CM list. The second assessed the same CM list with BIC/FTC/TAF. Each ART-CM combination was given a numerical score of 0 (no or potential weak interaction), 1 (potential interaction), or 2 (contraindicated interaction). Total DI scores for each patient, both before and after switching to BIC/FTC/TAF, were then calculated. A paired t-test analyzed changes in DI scores following ART switches and a linear regression model examined factors contributing to DI score reductions.

Results

A total of 411 patients were included in the analysis (Table 1) of which 236 (57%) had at least one DI present at baseline. On average, patients had a baseline DI score of 1.4 (SD 1.8) and experienced a 1 point reduction (95% CI -1.1,-0.8) after switching to BIC/FTC/TAF (p < 0.0001). After adjusting for demographic variables as well as baseline ART and CM categories in the regression model, switching to BIC/FTC/TAF led to significant DI score reductions in patients receiving CMs for the following conditions: cardiovascular disease, neurologic and psychiatric disorders, chronic pain, inflammation, gastrointestinal and urologic conditions and conditions requiring hormonal therapy (Table 2).

Table 1. Descriptive Summary of Baseline Characteristics, n =411.

Table 2. Linear Regression for the Difference of DI scores (post – pre), n =376.

Conclusion

Switching ART to BIC/FTC/TAF can reduce the incidence of DIs among treatment-experienced PWH who are receiving CMs for a broad range of comorbid conditions.

Disclosures

Jason J. Schafer, PharmD, MPH, Gilead (Research Grant or Support)Merck (Grant/Research Support, Advisor or Review Panel member)ViiV (Advisor or Review Panel member) Elizabeth Sherman, PharmD, Gilead (Grant/Research Support) Jennifer Cocohoba, PharmD, AAHIVP, BCPS, Viiv (Grant/Research Support)
1050. Hepatitis C Infection amongst People who Inject Drugs (PWID): Injection Practices and Risk Factors
Authors: Sankar Nityasri , Murray Kim , Burris Debra D , Thakarar Kinna
Published: January 2021

Background

The rapidly progressing U.S. opioid epidemic has led to an increased prevalence of infections associated with injection drug use (IDU), such as Hepatitis C (HCV). Previous studies have identified a lack of screening, prevention, and treatment of HCV, which has contributed to an increase in HCV-related mortality. Transmission has been linked to unsafe injection practices. Our study aims to characterize risk factors associated with Hepatitis C (HCV) exposure amongst people who inject drugs (PWID) in Maine, a state heavily impacted by the opioid epidemic.

Methods

Data was obtained from a cross-sectional study of participants hospitalized with an IDU-associated infection at four hospitals in Maine identified as high-risk for HIV/HCV outbreaks. The Audio Computer-Assisted Self-Interview survey and medical record review were used to collect data. The components from the BIRSI 7-item score were used to assess the use of safe injection practices. HCV exposure was defined as HCV antibody positive and/or self-reported exposure. Analysis was performed using descriptive analyses and univariate regression modeling.

Results

Of the 101 participants enrolled, n=76 (75%) were identified as having exposure to HCV. Out of participants exposed to HCV, 57% reported homelessness (p=< 0.01). Participants exposed to HCV were more likely to have bacteremia during hospitalization (25%, p=.02). All participants unexposed to HCV perceived low likelihood of contracting HCV due to injecting (p=.01). Seventy-one percent of people exposed to HCV reported infrequent use alcohol pads prior to injecting (p=< 0.01) and 67% reported infrequent hand-washing (p=.09). Participants with a higher BIRSI-7 score had higher odds of exposure to HCV (OR=1.48, 95% CI 1.10-2.04).

Conclusion

The data obtained highlights significant relationships between HCV exposure and certain risk factors. Homelessness was found to be associated with HCV exposure, suggesting an opportunity for more targeted intervention within this subgroup of PWID. Unsafe injection practices as measured by the BIRSI-7 score were related to HCV exposure, indicating educational opportunities about safe injection practices. Overall, targeted harm reduction services could be beneficial in the screening and prevention of HCV exposure amongst PWID.

Disclosures

All Authors: No reported disclosures
1054. A Randomized Controlled Trial of Hepatitis B virus (HBV) Revaccination among Men Who Have Sex with Men and Were Born in the Era of Universal Neonatal HBV Immunization
Authors: Huang Yi-Chia , Sun Hsin-Yun , Chuang Yu-Chung , Huang Sung-Hsi , Liu Wen-Chun , Su Yi-Ching , Chang Sui-Yuan , Hung Chien-Ching
Published: January 2021

Background

People who have lost anti-HBs antibody decades after neonatal vaccination but are at high risk of acquiring HBV are recommended to undergo HBV revaccination. The optimal revaccination strategy remains unknown, however. We aimed to compare the efficacy of revaccination with standard- (20-μg) vs double-dose (40-μg) of HBV vaccine among men who have sex with men (MSM).

Methods

MSM aged ≥ 20 years who had undergone HBV vaccination at birth and tested negative for HBsAg and anti-HBc with anti-HBs titer < 10 mIU/ml were randomized to receive standard- or double-dose HBV vaccine (1:1 ratio with a block size of 4) at weeks 0, 4, and 24. Plasma HIV RNA < 50 copies/ml for ≥ 6 months was required for HIV-positive MSM. The primary endpoint was the proportion of participants achieving anti-HBs ≥ 10 mIU/ml at week 28. The secondary endpoints were high-titer response (≥ 100 mIU/ml) at weeks 28 and 48, serological response at week 48, and adverse events (AE).

Results

From Sep 2017 to Jun 2020, 161 HIV-positive and 77 HIV-negative MSM were enrolled. The serological response at week 28 was 86.2% for the standard-dose group and 94.9% for the double-dose group (p=0.070). The proportion of high-titer response was higher for the double-dose group than the standard-dose group at 28 weeks (84.6% vs 70.1%, p=0.041). The respective serological response and high-titer response at week 48 were 81.3% and 58.7% for the standard-dose group vs 94.2% and 78.3% for the double-dose group (p=0.023 and p=0.013, respectively). In generalized estimating equations model, double-dose HBV revaccination (aOR, 1.7; 95% CI, 1.1-2.8) and baseline anti-HBs ≥ 2.5 mIU/ml (aOR, 7.5; 95% CI, 4.3-13.5) were associated with high-titer responses. HIV infection was not associated with serological response (aOR, -1.2; 95%CI, -2.47-1.60) and high-titer response (aOR, -1.1; 95%CI, -1.95-1.49). The double-dose group had a higher rate of local AEs (27.2% vs 38.7%, p=0.118). One (0.8%) severe AE occurred in the double-dose group, which resolved without sequelae.

Table 1. Baseline characteristic of participants

Table 2. Serological response after revaccination

Table 3. GEE model of vaccine efficacy and associated factors

Conclusion

Double-dose HBV revaccination results in sustained serological and high-titer responses among MSM who were born in the era of universal neonatal HBV vaccination. Anti-HBs titer ≥ 2.5 mIU/ml at baseline is associated with high-titer response.

Disclosures

All Authors: No reported disclosures
1063. Healthcare Utilization and Opportunities for HCV Testing and Treatment among Persons under Community Supervision in Pawtucket, RI
Authors: Dickerson Collin , Patry Emily J , Bazerman Lauri , Martin Johanna , Moody Marc , Beckwith Curt
Published: January 2021

Background

The burden of hepatitis C virus (HCV) is disproportionately borne by persons involved with the justice system. To explore missed opportunities for HCV screening and treatment among a justice-involved population, we examined healthcare utilization and prior opportunities for HCV testing and treatment among persons under community supervision enrolled in an HCV testing and linkage to care study in Rhode Island (RI).

Methods

Two hundred and fifty individuals under community supervision were recruited from an RI probation and parole office. Participants underwent a rapid HCV antibody test (OraSure Technologies) and a baseline survey, which queried participants on justice involvement, demographics, substance use, healthcare utilization and prior HCV testing. A positive HCV antibody test and no report of previous HCV testing was classified as a missed opportunity for testing. Self-reported prior HCV diagnosis with no history of treatment was classified as a missed opportunities for HCV treatment.

Results

Forty-five participants (18%) had reactive antibody tests. Of those 45, twenty-five (55%) reported previously being diagnosed with HCV, including thirteen who reported an HCV diagnosis over 10 years ago; none had received HCV treatment. In addition, 135 participants (61.1%) reported previously being tested for HCV; the most common site of prior testing was in jail/prison (n=87). Ten participants had missed opportunities for HCV testing, and 25 had missed opportunities for HCV treatment. Of participants with these missed opportunities, 97% had health insurance, 74% had been to a primary care provider in the past year, and 91% had ≥ 1 identifiable risk factor for HCV.

Flowchart of HCV Antibody Test Results and History of HCV Testing

Healthcare Utilization among Persons with Missed Opportunities

Conclusion

Screening for HCV at community supervision sites is an underutilized venue for HCV screening that can identify previously-undiagnosed HCV infections. Many persons under community supervision are aware of their HCV positive status but have never received treatment. Despite involvement in healthcare systems and adequate health insurance coverage, many patients with risk factors for HCV have not been tested for HCV or have only been tested for HCV while incarcerated. Investing in and implementing strategies to increase testing for HCV is necessary to maximize the care continuum in this priority population.

Disclosures

All Authors: No reported disclosures
80. Pharmacoeconomic Analysis Comparing the Empiric Utilization of Cefepime Versus Piperacillin/tazobactam
Authors: Olmack Kelsey , Collins Curtis D
Published: January 2021

Background

In the hospital setting, cefepime (CFP) and piperacillin/tazobactam (PTZ) are among the most commonly utilized antipseudomonal agents in the empiric treatment of nosocomial and healthcare-associated infections. Institutional preference of CFP or PTZ as the preferred antipseudomonal antibiotic varies. Recent literature suggests each may be associated with increased rates of harmful adverse effects including Clostridiodes difficile infection (CDI) and acute kidney injury (AKI). The objective of this study is to perform a pharmacoeconomic analysis comparing CFP versus PTZ for empiric antibiotic treatment in patients where Pseudomonas aeruginosa is a concern.

Methods

We performed a cost-utility analysis comparing CFP and PTZ for empiric utilization in the hospital setting by creating a decision analytic model from the hospital perspective. Model variables were populated utilizing published clinical and economic data including incidence of AKI and CDI, their associated costs and mortality, and the cost of antibiotic therapy. Secondary and univariate sensitivity analyses tested the impact of model uncertainties and the robustness of our model. A willingness to pay (WTP) threshold of $0 was utilized.

Results

Results of our base-case model predicted that the use of CFP dominated PTZ as empiric utilization was less expensive ($7690 vs. $9331) and associated with a higher quality-adjusted life-years (QALY) (0.9193 vs. 0.9191) compared to the use of PTZ. Several variables had the potential to impact base case results. PTZ became cost-effective at our WTP threshold if CFP nephrotoxicity rates increased to 17.3%, the PTZ nephrotoxicity decreased to 28.5%, or if the cost of nephrotoxicity was less than $17,457. No other model variables, including incidence of CDI, impacted base case results.

Sensitivity Analysis on Cefepime Clostridioides difficile Infection Incidence and Piperacillin/tazobactam Nephrotoxicity

Conclusion

Results of our model showed that CFP dominated PTZ for the empiric treatment of nosocomial infections. The model was sensitive to variation in CFP and PTZ nephrotoxicity rates.

Disclosures

All Authors: No reported disclosures
1070. Risk factors for failed linkage to Hepatitis C care
Authors: Palacios Carlo Fopiano , Hynicka Lauren , Schmalzle Sarah
Published: January 2021

Background

Many patients with Hepatitis C (HCV) who are referred to HCV care do not attend their HCV clinic appointments. As social determinants of health are known to affect HCV acquisition, we sought to evaluate their role on successful linkage to HCV care also.

Methods

A retrospective chart review was conducted on patients with both a positive HCV antibody or RNA test and a scheduled but not-attended infectious disease (ID) clinic appointment in 2017. Abstracted data included patient demographic, type of insurance, HCV test results, and risk factors that may impair outpatient HCV linkage. Descriptive statistics, chi-square, and Fisher exact tests were performed. We sought to identify the factors limiting patients with HCV from attending their first clinic visit.

Results

There were 161 out of 1539 patients (10%) who did not keep their HCV clinic appointment. The mean age was 48 years, 45% were female, and the majority were African American (61%). Most patients had insurance that was accepted by the HCV clinic (76%) and had been tested for HCV while admitted to the hospital (94%). Almost all patients had been tested both for HCV antibodies (98%) and viral RNA via PCR (97%). Risk factors known to contribute to unsuccessful linkage to care were common: substance use (85%), mental health diagnosis (71%), inadequate transportation (66%), housing insecurity (61%), history of medication nonadherence (61%), and alcohol use (52%). Seven patients (4%) died by the end of 2017. Patients alive at the end of 2017 were more likely to have insurance accepted at the ID clinic compared to those without accepting insurance (98% vs. 90%, p 0.06).

Conclusion

Significant barriers are present among patients with HCV who were not successfully linked to a scheduled HCV appointment. Patients with HCV should be provided additional support as appropriate to address the social determinants of health that may limit their linkage to HCV care. Lack of accepted insurance at the ID clinic was associated with mortality and warrants further investigation into its causes.

Disclosures

All Authors: No reported disclosures
1074. Understanding Screening Practices for Hepatitis B Prior to Starting Biologics at an Academic Medical Center
Authors: Jhaveri Tulip A , Higgs James B , Hopkins Mary J
Published: January 2021

Background

It is estimated that 0.3% of the US population has chronic hepatitis B (HBV) infection, most of whom are asymptomatic. When a patient receives a biologic medication, chronic HBV can reactivate with mortality rates as high as 40%. We aim to understand HBV screening practices prior to starting biologics at a single tertiary academic medical center.

Methods

We retrospectively reviewed over 500 patient charts. These patients aged ≥ 18 years were prescribed a biologic medication at one of the three clinics (Dermatology, Rheumatology, or Gastroenterology) at Tufts Medical Center from January 2016 to April 2019. To determine the rate of HBV screening compliance, we reported the proportion of patients who had appropriate HBV serologies (HBV surface antigen and HBV core antibody) drawn prior to initiation of the biologic therapy. A survey was sent to providers from these departments to understand their current practices of HBV screening.

Results

133 of 541 patients (25%) had been appropriately screened for HBV within six months prior to starting biologic therapy. 207 of 541 (38%) had been screened with appropriate serologies within ten years prior to starting a biologic. 23 providers participated in the survey, 7 each from the department of Rheumatology and Gastroenterology, and 9 from Dermatology. One-third of the providers were currently in training, another third were practicing for < 5 years, and the remainder had > 5 years of experience. 57% of the providers said they would screen everyone for HBV before starting a biologic. 78% of them chose the appropriate serologies. The time interval for rescreening was evenly spread amongst different providers, ranging from 3 months to 5 years. If a patient was switched to a new biologic, 48% of physicians would repeat screening only if the patient was determined to be at risk of reactivation or new acquisition of HBV. The major barrier to screening was uncertainty regarding who to screen and which tests to order.

Conclusion

This data reveals that there is inadequate screening for HBV prior to biologic therapy. The survey highlighted areas for quality improvement, including the need for wider dissemination of screening guidelines and development of a protocolized approach to ordering the correct tests.

Disclosures

All Authors: No reported disclosures
1077. Infectious complications after second allogeneic hematopoietic cell transplant (allo-HCT) in adult patients with hematological malignancies
Authors: Maurer Stephen , Linder Kathleen A , Kauffman Carol A , McDonald Philip , Arcobello Jonathan T , Velasco Jon Karl D , Chandrasekar Pranatharthi , Revankar Sanjay , Miceli Marisa H
Published: January 2021

Background

A 2nd allo-HCT is received by some adults after relapse of their underlying malignancy, development of a second malignancy, or graft failure. Few studies have reported on infectious complications in adults given a 2nd HCT

Methods

This is a retrospective review of infectious complications and overall mortality of 60 adult patients who received a 2nd HCT from Jan. 2010 - Dec. 2015. Data were collected for 2 years post-HCT for each patient. Infections were separated into < 30 days (d) post-HCT, 30-100d post-HCT, and >100d post-HCT.

Results

Mean age at 2nd HCT was 49+13; 60% were men. The most common reason for the 1st HCT was acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) (73%,n= 44) The 2nd HCT was for relapse of original malignancy (62%,n=37), graft failure (27%,n=16), and new malignancy (10%,n=6). The 2nd HCT was received a median of 344d (range 29-8248) after 1st HCT. Neutrophil engraftment occurred by 13+4d in 50/60 patients.

Fifty-eight patients (97%) had at least one infection during the study period. A total of 183 infections were reported: 75 (41%) were < 30d, 56 (31%) 30-100d, and 52 (28%) >100d post-HCT. Bacterial infections, primarily C. difficile, vancomycin-resistant Enterococcus, and coagulase (-) Staphylococcus caused 90 (49%) infections and were seen throughout the post-HCT period. Viral infections, predominantly CMV and BK virus, caused 60 (33%) of infections, peaking at 30-100d post-HCT. Only 19 (10%) infections were fungal, most of which were mold infections and occurred >30d post-HCT.

Thirty-nine (65%) patients died by 2 years post-HCT, 27 within the first year. Cause of death was infection in 16 (41%), graft failure, relapse, or GVHD in 16 (41%), other in 7 (18%). At < 30d post-HCT, 5 deaths (71%) were from infection 4 of which were bacterial. At 30-100d post-HCT, 6/9 (69%) deaths were from relapse/graft failure/GVHD. All 6 deaths from fungal infections were >100d post-HCT. Bacterial Infections and engraftment failure within 100d post-HCT were associated with increased mortality (p .05 and < .001, respectively).

Conclusion

All but 2 patients receiving a 2nd allo-HCT developed an infection. Most deaths at < 30d post-HCT were from infection. Overall 2-year mortality was 65% and 41% of deaths were related to infection.

Disclosures

Marisa H. Miceli, MD, FIDSA, SCYNEXIS, Inc. (Advisor or Review Panel member)
1088. Extracorporeal Photopheresis and Infectious Complications in Patients with Chronic Graft Versus Host Disease
Authors: Ashraf Nida , Dias Ajoy , Clough Lisa A , Ni Yonghui , Chalise Prabhakar , Atrouni Wissam El
Published: January 2021

Background

Extracorporeal photopheresis (ECP), is a cell-based immune-modulatory therapy used in the treatment of steroid refractory chronic graft versus host disease (cGHVD). It is unclear whether ECP is associated with an increased risk of infections compared to alternative treatment. We aimed to study the infectious complications in patients who are on ECP post allogeneic hematopoietic stem cell transplant (alloHSCT).

Methods

We conducted a retrospective cohort study of adult patients with cGVHD post alloHSCT who were initiated on ECP or second line immunosuppressive agents (SLIS). The study period was from March 1, 2014 to October 1, 2018. Each subject in the ECP arm was matched to the SLIS arm according to gender, age, underlying disease, and date of diagnosis of cGVHD. All subjects were followed for one-year post treatment. The main outcome was incidence of each type of infection (event rate/ person-years). Kaplan Meier analysis was used, evaluating time to infection with log rank test. The spectrum of infectious complications was described.

Results

Seventy-seven patients were included (36 in ECP and 41 in SLIS arm). Median age was 57.4 years (18.1 -73.4), and 59.7% of patients were male. The most common underlying diseases were acute myeloid leukemia (45.4%), myelodysplastic syndrome (20.8%) and non-Hodgkin’s lymphoma (15.6%). A total occurrence of 94 infections was observed in the ECP arm, compared to 118 in SLIS arm. Bacterial infections accounted for majority of the infections in ECP arm (50%) compared to SLIS arm in which viruses were most common (49.2%). Bacterial pneumonia was the most common clinical syndrome (34% and 27.3%, in the ECP and SLIS arms, respectively). Bacteremia accounted for 12.8% of infections in the ECP arm compared to 16.4% in the SLIS arm. There was no difference in the event rates of infections among the two groups [2.58/ person-years in ECP group vs 3.60/person-years, p = 0.3766], or the probability of infection at any time between the ECP and SLIS group on Kaplan Meier (log rank test, p-value=0.36)(Figure 1).

Kaplan-Meier plot of time to the earliest infection diagnosis between ECP and control group

Conclusion

Bacterial and viral pneumonia were the most common infections in patients undergoing ECP. Overall, ECP does not confer an increased risk of infectious complications compared to second line IS agents.

Disclosures

Wissam El Atrouni, MD, ViiV (Advisor or Review Panel member)
1095. Investigation of Risk Factors Associated with Serious Bacterial, Viral and Invasive Fungal Infections in Hematologic Patients on Ibrutinib
Authors: Holowka Thomas , Cheung Harry , Malinis Maricar F , Perreault Sarah , Isufi Iris , Azar Marwan M
Published: January 2021

Background

Ibrutinib is a tyrosine kinase inhibitor used to treat hematologic malignancies that may increase the risk of serious infection including invasive fungal infections (IFI). In a study of 378 patients with hematologic malignancy on ibrutinib, serious infection and IFI occurred in 11% and 4% respectively (Varughese et al. Clin Infect Dis). The primary aims of our study were to determine the incidence of serious infection and associated risk factors in patients on ibrutinib.

Methods

We performed a retrospective analysis of patients with hematologic malignancy prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital from 2014 to 2019 to identify serious infections defined as those requiring inpatient management. We collected demographic, clinical and oncologic data. Chi-squared tests were used to determine factors associated with an increased risk of infection.

Results

A total of 254 patients received ibrutinib including 156 with CLL, 89 with NHL and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. There were 51 (20%) patients with serious infections including 45 (17.7%) bacterial, 9 (3.5%) viral and 5 (2%) IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis). Anti-mold prophylaxis was prescribed to 7 (2.8%) patients, none of whom developed IFI. Risk factors associated with serious infection included ECOG score ≥ 2 (OR 4.6, p < 0.001), concurrent steroid use (≥ 10 mg prednisone daily for ≥ 2 weeks; OR 3.0, p < 0.001), neutropenia (OR 3.6, p < 0.01), lymphopenia (OR 2.4, p < 0.05) and maximum ibrutinib dose of 560 mg (OR 2, p < 0.05). There was a dose dependent increase in infections based on number of chemotherapy regimens prior to ibrutinib initiation: 14.3% with 0, 19.7% with 1-2 and 28.7% with ≥ 3 prior treatments.

Conclusion

The incidence of serious infection in hematologic patients on ibrutinib was higher than previously reported (20% versus 11%) but the rate of IFI was lower (2% versus 4%). High ECOG score, leukopenia, steroids, and higher ibrutinib doses were associated with an increased risk for serious infection. Targeted antimicrobial prophylaxis should be considered for patients on ibrutinib with these risk factors. Improving functional status may also reduce the risk of infection in patients on ibrutinib.

Disclosures

All Authors: No reported disclosures
1107. Third Generation Cephalosporins Monotherapy Experience in Pediatric Patients with High-Risk Febrile Neutropenia
Authors: Gutierrez Valentina , Claverie Ximena
Published: January 2021

Background

Fever during neutropenia is common in children with cancer. The updated guidelines recommend empirical antibiotic monotherapy using an antipseudomonal ß-lactam, a fourth generation cephalosporin or a carbapenem for high-risk febrile neutropenia. However, local epidemiology and resistance patterns should be evaluated regularly. In our hospital there are not Pseudomonas aeruginosa isolates in oncology pediatric patients, therefore, we use ceftriaxone as monotherapy in high risk febrile neutropenia without other risk factors. The goal of our investigation is to describe the experience of using third generation cephalosporins in these patients.

Methods

Descriptive study of high-risk febrile neutropenia episodes in patients admitted to the Pediatric Oncology Unit of Hospital Dr. Sótero del Río, Santiago, Chile. We included patients ≤15 years from June 2016 until December 2019.

Results

We found 140 episodes in 53 patients, 42 (79%) were leukemia and 11 (21%) solid tumor patients. Of the 140 episodes, 97 (69%) had clinical signs at admission, mostly respiratory in 48 (49%) of the cases. Ninety one (65%) cases started ceftriaxone at admission, 27 (30%) maintained ceftriaxone for 7 days of treatment. Sixty four (70%) cases changed treatment: 38/64 (42%) started second line antibiotics for clinical worsening, 19/64 (20%) required second and third line antibiotics for persistent fever and clinical worsening, and 7/64 (8%) received third line antibiotics from the start for past microbiological history. Eighteen (13%) cases evolved with sepsis requiring intensive care unit management.We had 32 (23%) episodes with positive blood culture, 13 (41%) due to gram positive bacteria, 16 (50%) gram negative bacteria, and 3 (9%) cases of fungal infections. Of the gram negative bacteria, 7 (44%) were ESBL producers, without Pseudomonas aeruginosa isolates.One case died (0.7%) for refractory sepsis due to gram negative bacteria.

Conclusion

Monotherapy with ceftriaxone is not a good option as initial therapy for high risk febrile neutropenia patients due to the spread of ESBL strains. The empiric therapy has to be evaluated regularly and should always be based in local epidemiology.

Disclosures

All Authors: No reported disclosures
1113. A Novel Means of Acquiring High Quality Feedback for Training Programs –The Program Director Ombudsperson
Authors: Riedel David J , Malek Rana
Published: January 2021

Background

Trainees may not always be comfortable providing frank feedback or constructive criticism to their Program Director (PD) due to fears of negative repercussions. PDs likewise may lack the means to obtain high quality feedback from trainees, particularly among smaller training programs, e.g. fellowships. An ombudsperson is defined as an independent appointee whose task is to investigate and attempt to resolve complaints and problems.

Methods

The PDs from Infectious Disease (ID) and Endocrinology fellowships partnered to meet with fellows from the opposite program. Meetings were held with fellows in December and June of the academic year. Each PD started their meeting with 2 questions on a 1-10 scale: How do you rate the fellowship program? How do you rate the job the PD and program leadership are doing? Additional questions covered the fellow evaluation process, faculty feedback, education vs. service balance, and gaps in training. Additional time was allotted for fellow-raised concerns. Meeting notes were summarized anonymously and returned to the PD of the other program. Fellows were asked to complete a brief questionnaire about their experience.

Results

A total of 15 fellows completed the survey (6 Endocrinology, 9 ID; Table). All 15 fellows agreed that the goal of the ombudsperson review meeting (i.e. to address fellow concerns in a more confidential setting) was achieved and were comfortable sharing concerns and feedback to the ombudsperson. The majority of fellows (53%) was more comfortable sharing concerns regarding the fellowship to the ombudsperson than directly to the PD. Thirteen (87%) agreed that concerns raised during the first ombudsperson meeting were addressed by the Program in subsequent months. All fellows (100%) found it helpful that the ombudsperson was another PD and recommended that the ombudsperson review meetings should continue in the fellowship.

Table. Characteristics of participants and outcomes of questions about fellowship ombudsperson program

Conclusion

The fellowship PD ombudsperson meeting is a novel means for soliciting constructive feedback from trainees at small training programs. Fellows were comfortable with the ombudsperson arrangement, felt the meetings achieved their goal, and recommended that the meetings continue in the future.

Disclosures

All Authors: No reported disclosures
1117. An HIV Primary Care Rotation Improved HIV and STI Knowledge, Enhanced Sexual History-Taking Skills, and Increased Interest in a Career in Infectious Diseases among Medical Students and Residents
Authors: Wooten Darcy , Marshall Austin
Published: January 2021

Background

Clinical rotations in HIV primary care provide a unique opportunity to teach trainees about the management of HIV and other sexually transmitted infections (STI), and enhance trainees’ skills in obtaining a culturally-competent sexual history. Positive educational experiences in this setting may also influence trainees’ decisions to pursue a career in HIV Medicine and Infectious Diseases (ID). However, little is known about the impact of an HIV clinic rotation on trainees’ fund of knowledge regarding HIV and STI management, confidence in obtaining a sexual history, or interest in HIV and ID as a career choice.

Methods

Third year medical students and Internal Medicine residents rotate for two to four weeks in UCSD’s HIV primary care clinic. Over a six month period (September, 2019 - February, 2020) trainees were given a pre and post rotation survey to evaluate their fund of knowledge in managing patients with HIV and other STIs, their confidence in taking a sexual history, and their interest in pursuing a career in HIV and ID.

Results

Twenty-one of the 31 trainees completed both the pre- and post-rotation survey. Residents and medical students comprised 57% (12) and 43% (9) of the cohort, respectively. Fund of knowledge regarding antiretroviral management, HIV transmission, and STI diagnosis and treatment improved following the rotation (Figure. 1). Trainees’ confidence in their ability to manage patients with HIV and obtain a sexual history also improved (Figure. 2). Importantly, there was a substantial increase in the proportion of trainees interested in pursuing a career in HIV and ID after the rotation compared to beforehand (Figure. 2).

Fund of Knowledge Pre and Post Rotation

Self-Perceived Competency and Interest in HIV Clinical Care

Conclusion

Clinical rotations in HIV primary care provide valuable learning experiences for trainees by improving their fund of knowledge about HIV and STIs, and their self-efficacy in obtaining a sexual history. These clinical experiences may also be important in recruiting trainees to pursue a career in HIV and ID. Given the importance of these clinical skills and the need to increase the number of trainees entering the field, additional support for educational experiences in HIV primary care clinics is warranted.

Disclosures

All Authors: No reported disclosures
1128. Online Spaced Education to Teach Microbiology to Medical Students in a Threaded Medical School Curriculum
Authors: Sathe Nishad , Bonura Erin
Published: January 2021

Background

A strong foundation in microbiology continues to be essential for physicians-in-training. Little research exists examining pre-clinical microbiology education in undergraduate medical education (UME) curricular structures. Further, no study has evaluated the use of a spaced repetition model for pre-clinical UME students studying microbiology in a threaded curriculum.

Methods

We conducted a prospective cohort design study and enrolled 81 out of 154 (53%) first-year medical students at Oregon Health & Science University from August 2018 through December 2019. The first 18 months of the UME curriculum is organized by organ system blocks with end-of-block exams including retired National Board of Medical Examiner (NBME) questions. Participants were invited to complete 10 microbiology questions using the spaced practice online platform QSTREAM weekly. Performance between participants and non-participants on end of block NBME exams were compared using t-tests for categorical variables.

Results

At the conclusion of the study, 42.5% of participants were “very active” (questions in < 2 days), 7.5% of participants were “active” (questions in 3-7 days), and 50.0% of participants were “inactive” (questions in >7 days). Student performance on second-pass questions improved by 41%, and NBME end-of-block exams demonstrated improved performance in each block compared to non-participants. Specifically, performance in the Skin, Bones, and Musculature end-of-block exam and Developing Human end-of-block exam was significantly (p=0.0001, 0.008, respectively) improved, and study participants outperformed non-participants on topics practiced in the study.

Conclusion

As more medical schools move to a threaded curriculum, with many of these programs proposing fewer contact hours, innovative methods targeting microbiology education should be explored for pre-clinical medical students. Online spaced practice in a threaded curriculum could provide a feasible and acceptable pedagogical technique for UME and add to the discourse around microbiology curriculum development. With initial start-up costs, sustaining such a program across medical school curricula is an inexpensive, innovative, technologically-savvy approach to medical education.

Disclosures

All Authors: No reported disclosures