bluuebunny/crossref_metadata_2025_split huggingface dataset:
875. Indirect Treatment Comparison of 48-Week Efficacy and Safety of Cabotegravir + Rilpivirine Long-Acting Every 2 Months to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Suppressed HIV-1 Infected Participants
Authors: Snedecor Sonya J , Schroeder Melanie , Van de Velde Nicolas 
Published: December 2021

Abstract

Background
Switching to cabotegravir long-acting + rilpivirine long-acting (CAB LA + RPV LA) administered every month (Q1M) has demonstrated non-inferiority in viral suppression versus a range of standard of care (SoC) antiretroviral regimens, including tenofovir alafenamide based regimens, in two pivotal phase 3 clinical trials (ATLAS [NCT02951052] and FLAIR [NCT02938520]). Furthermore, CAB LA + RPV LA every 2 months (Q2M) has demonstrated non-inferiority in maintaining viral suppression compared with CAB LA + RPV LA Q1M in a phase 3b study (ATLAS-2M [NCT03299049]). As bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) was not widely used at study initiation, the regimen was not present in the SoC arms of ATLAS and FLAIR. The objective was to compare efficacy and safety of CAB LA + RPV LA Q2M to BIC/FTC/TAF using indirect treatment comparison.

Methods
Two switch studies appropriate for facilitating indirect comparison to BIC/FTC/TAF were identified via systematic literature review (Molina et al. 2018 [NCT02603120] and Sax et al. 2020 [NCT03110380]). Indirect comparison using a generalisation of Bucher’s methodology to calculate relative risk, odds ratio, and risk differences in efficacy (Week 48 HIV RNA &lt; 50 c/mL and ≥50 c/mL per FDA Snapshot approach and CD4+ cell change from baseline) and safety (discontinuation due to adverse events [AEs] and overall and serious AEs excluding injection site reactions [ISRs]) was conducted. Results for CAB LA + RPV LA Q2M in ATLAS-2M participants with prior integrase inhibitor (INI) exposure, but without prior CAB exposure, were indirectly compared to those with prior INI use in ATLAS and FLAIR via the common CAB LA + RPV LA Q1M comparator and were then indirectly compared to BIC/FTC/TAF via the INI comparator (Figure 1).

Results
No statistically significant differences in virologic failure, virologic suppression, CD4+ cell change, discontinuations due to AEs, and non-ISR serious/non-serious AEs were found between CAB LA + RPV LA Q2M and BIC/FTC/TAF (Table 1).

Conclusion
Indirect treatment comparison indicated efficacy and safety of CAB LA + RPV LA Q2M is not different from BIC/FTC/TAF. These regimens will be further compared in a randomized head-to-head non-inferiority trial (SOLAR, NCT04542070).

Disclosures
Sonya J. Snedecor, PhD, ViiV Healthcare (Other Financial or Material Support, Author’s employer, OPEN Health received funding to execute this study) Melanie Schroeder, MSc, ViiV Healthcare (Employee) Nicolas Van de Velde, PhD, ViiV Healthcare (Employee)
888. In Vitro Forgiveness of INSTI-Containing Regimens at Drug Concentrations Simulating Variable Adherence
Authors: Acosta Rima K , Mulato Andrew , D’Antoni Michelle L , Yant Stephen R , Cihlar Tomas , White Kirsten L 
Published: December 2021

Abstract

Background
The integrase strand transfer inhibitor (INSTI)-based regimens bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), dolutegravir (DTG)+FTC/TAF, DTG/lamivudine (3TC), and DTG/rilpivirine (RPV) are all used for treatment of HIV-infected patients. Here, relative time to in vitro viral breakthrough (VB) and resistance barrier using simulated human drug exposures at either full or suboptimal treatment adherence to each regimen were compared.

Methods
Wild-type HIV-1 (IIIb)-infected MT-2 cells were exposed to the combinations of BIC+FTC+TAF, DTG+FTC+TAF, DTG+3TC, or DTG+RPV for up to 35 days or until VB. Fixed drug concentrations were the human plasma-free adjusted clinical trough concentrations (Cmin) or fixed at simulated Cmin after missing 1 to 4 consecutive doses (Cmin-1 to -4), with many replicates. Drug resistance was studied by next-generation sequencing at ≥2% frequency.

Results
At drug concentrations corresponding to full adherence and 1 missed dose (Cmin and Cmin-1), no VB occurred with any regimen (Table). At Cmin-2, only DTG+3TC had VB, with some emergent resistance to both drugs. At Cmin-3, all regimens had VB: by day 12, 100% of DTG+3TC wells had VB; for BIC+FTC+TAF, DTG+FTC+TAF, and DTG+RPV, &lt; 15% of wells had VB which began after day 14. Emergent RT or IN resistance was seen for DTG+RPV and DTG+3TC but not for BIC+FTC+TAF or DTG+FTC+TAF. At Cmin-4, all DTG+3TC and DTG+FTC+TAF wells had VB by day 12, while DTG+RPV had 94% VB by day 25 and BIC+FTC+TAF had 50% VB by day 35. Emergent Cmin-4 drug resistance was seen for all regimens but at differing frequencies; DTG+RPV had the most wells with resistance. Cumulatively, emergent RT and/or IN resistance was found in 1.3% BIC+FTC+TAF, 2.5% DTG+FTC+TAF, 7.9% DTG+3TC, and 8.8% DTG+RPV cultures.
Summary of Forgiveness and Barrier to Resistance of INSTI-Containing Regimens

Conclusion
Regimen forgiveness and resistance barrier are important factors in long term treatment. These INSTI-based regimens had high in vitro forgiveness and resistance barriers with concentrations simulating high adherence. When multiple missed doses were simulated in vitro, BIC+FTC+TAF had the highest forgiveness and barrier to resistance. When compared to DTG+3TC and DTG+FTC+TAF, DTG+RPV had higher forgiveness but lower resistance barrier after several simulated missed doses.

Disclosures
Rima K. Acosta, BS, Gilead Sciences, Inc. (Employee, Shareholder) Andrew Mulato, BS, MBA, Gilead Sciences, Inc. (Employee, Shareholder) Michelle L. D’Antoni, PhD, Gilead Sciences (Employee, Shareholder)Gilead Sciences, Inc (Employee, Shareholder) Stephen R. Yant, PhD, Gilead Sciences, Inc. (Employee, Shareholder) Tomas Cihlar, PhD, Gilead Sciences, Inc. (Employee, Shareholder) Kirsten L. White, PhD, Gilead Sciences, Inc (Employee, Shareholder)
896. Examining the Impact of the COVID-19 Pandemic on Delivery of HIV Care and Prevention Services Among Patients in a Ryan White Clinic
Authors: Zhang Michelle , Butler Sharlay , Kennedy Jason , McKune Molly , Haidar Ghady , McMahon Deborah 
Published: December 2021

Abstract

Background
We sought to characterize the impact of the COVID-19 pandemic on HIV-related outcomes in a cohort of patients by examining rates of viral load (VL) suppression, retention-in-care, PrEP access, and STIs.

Methods
This was a single center, retrospective study of adults receiving HIV treatment or HIV/STI prevention services from 01/2019 - 12/2020. HIV outpatient visits were identified through HRSA’s CareWARE. Visits (in-person, telehealth) only included HIV primary care. HRSA core performance measures were utilized (Table 1). STI positivity rates and descriptive characteristics were calculated. New and refill PrEP prescriptions were tabulated. Chi-square tests compared unmatched non-parametric variables; McNemar’s test matched non-parametric variables. Multivariable logistic regression identified variables associated with retention in care and viral suppression.

Results
1721 patients received care; 1234 were seen in both years, 334 only in 2019, 153 only in 2020. The number of telehealth visits increased significantly: video (0% to 31%, &lt; 0.001), phone (0% to 0.4%, p &lt; 0.001). Though the proportion of kept appointments increased (57.2% vs 61.2%), the annual retention in care rate decreased from 74.5% to 70.9% (p = 0.002). Overall, 9.7% of patients had detectable VLs at any point. Compared to 2019, a lower proportion of patients maintained VL suppression in 2020, (91.6% vs 83.5% p = 0.075). More patients did not have a VL drawn in 2020 than in 2019 (10.3% vs 2.0 %, p &lt; 0.001). Patients with detectable VLs in 2019 were more likely than those who were undetectable to have detectable VLs in 2020 (OR 18.2, 95% CI 9.91-33.42). Black race was associated with higher likelihood of lack of VL suppression (OR = 2.0; 95% CI 1.10-3.66). There were no significant differences between gender or age groups in rates of viral suppression, number screened for bacterial STIs or positive results. Visits for new and refill PrEP prescriptions decreased by 59% and 7%, respectively.

Conclusion
Rates of viral load suppression and retention in care decreased in 2020 compared to 2019. The proportion of clinic visits attended increased after the integration of telemedicine in 2020. These data may be used to inform evidence-based interventions to improve the HIV continuum of care through telehealth.

Disclosures
Ghady Haidar, MD, Karuys (Grant/Research Support)
905. Risk of Hepatitis B Reactivation in Patients Receiving Ibrutinib: The National VA Cohort
Authors: Chen Ting-Yi , Jacob David , Coppin John David , Jinadatha Chetan 
Published: December 2021

Abstract

Background
Ibrutinib, a bruton tyrosine kinase inhibitor was approved by Food and Drug Administration (FDA) in 2013 and became the first-line treatment for chronic lymphocytic leukemia in 2014. The risk Hepatitis B Virus (HBV) reactivation after initiation of ibrutinib is unclear. Here, we report the results of national Veterans Health Administration (VHA) pharmacy database review estimating the incidence of HBV reactivation after initiation of ibrutinib.

Methods
Veterans who received ibrutinib between Feb 1, 2014 through October 31, 2019 were included in our study. Possible reactivations were identified by change of Hepatitis B Virus surface antigen (HBV sAg), HBV core antibody (Ab) or HBV viral load from no data or negative to positive after starting ibrutinib. Individual chart review was conducted to verify HBV reactivation due to ibrutinib. Cumulative incidence was calculated by identifying HBV reactivation cases among at risk patients, which was defined as prior exposure by positive HBV core Ab regardless of HBV sAg or HBV viral load status. For patients without any HBV serology, an estimated prevalence of HBV exposure in veterans from the literature is used.

Results
A total of 4130 veterans were on ibrutinib during the study period. Of 4130 patients, 1875 patients with HBV core Ab negative and 68 patients on antivirals against HBV prior to ibrutinib were excluded. Among the remaining 2187 patients, there were 170 patients with positive HBV core Ab and 2017 patients without HBV core Ab tested regardless of HBV sAg or HBV DNA status. We used the estimated 13.6% (95%CI 11.5-16.1) of HBV exposure in veterans and estimated that 274 (95%CI 232-325) out of 2017 patients would be at risk of HBV reactivation. Thirty-nine patients were identified to have HBV reactivation after ibrutinib. After detailed review, 7 HBV reactivations were attributable to initiation of ibrutinib. The cumulative incidence of HBV reactivation after ibrutinib was estimated as 1.5% (95% CI 1.4-1.7).

Conclusion
In this large VHA study, we identified 7 cases of HBV reactivations among 444 at risk patients. The cumulative incidence of HBV reactivation after ibrutinib was 1.5% in patients with prior HBV exposure with positive HBV core Ab irrespective of HBV sAg or HBV DNA status, indicating a moderate risk of HBV reactivation.

Disclosures
All Authors: No reported disclosures
111. Duration of Antibiotic Therapy after Debridement and Implant Retention in Patients with Periprosthetic Joint Infections
Authors: Tai Don Bambino Geno , Berbari Elie , Abdel Matthew P , Lahr Brian , Tande Aaron J 
Published: December 2021

Abstract

Background
Debridement, antibiotics, and implant retention (DAIR) is appropriate for select acute postoperative and hematogenous periprosthetic joint infections (PJIs). However, the optimal duration of antimicrobial therapy in patients treated with DAIR has not been defined. Therefore, we aimed to identify the ideal duration of parenteral and oral antibiotics after DAIR.

Methods
We performed a retrospective study of patients &gt;18 years of age with hip or knee PJI managed with DAIR between January 1, 2008, and December 31, 2018, at Mayo Clinic. PJI was defined using criteria adapted from the International Consensus Meeting on PJI. The outcome was defined as either PJI recurrence or unplanned reoperation due to infection. Joint-stratified Cox proportional hazards regression models with time-dependent covariates were used to assess nonlinear effects of antibiotic duration. Hazard ratios were computed based on prespecified time points for comparison, whereas p-values represented the overall effect across the entire range of durations.

Results
There were 247 unique episodes of PJI in 237 patients during the study period. Parenteral antibiotics were given in 99.2% of cases (n=245). This was followed by chronic oral antibiotic suppression in 92.2% (n=226) with a median duration of 2.2 years (1.0-4.1).
DAIR failed in 65 cases over a median follow-up of 4.4 years, with a 5-year cumulative incidence of 28.1%. After adjustment for risk factors, there was no significant association between duration of parenteral antibiotics and treatment failure (p=0.203), with no difference between four versus six weeks (HR 1.11; 95% CI 0.71-1.75) (Figure 1). However, both use and longer duration of oral antibiotic therapy was associated with a lower risk of failure (p=0.006). To account for the possibility that this association was driven by results during early follow-up, conditional analyses at one- and two-year follow-up were performed. Both showed a significantly lower risk for a longer duration of antibiotics (Figure 2).
Figure 1. Time-Dependent Analysis of Parenteral Antibiotic Duration

Figure 2. Time-Dependent Analysis of Oral Antibiotic Suppression Duration

Conclusion
After DAIR, efficacy from four weeks of parenteral antibiotics was no different from six weeks when followed by chronic oral antibiotic suppression. Our results could not establish an optimal duration but suggested that continuing suppression portends a lower risk of failure of DAIR.

Disclosures
Elie Berbari, MD, Uptodate.com (Other Financial or Material Support, Honorary unrelated to this work) Matthew P. Abdel, MD, Stryker and AAOS Board of Directors (Board Member, Other Financial or Material Support, Royalties) Aaron J. Tande, MD, UpToDate.com (Other Financial or Material Support, Honoraria for medical writing)
917. Accessible HCV Care for People Who Inject Drugs: Randomized Clinical Trial Comparing Low-Threshold Treatment at a Syringe Service Program Versus Facilitated Referral
Authors: Eckhardt Benjamin , Aponte-Melendez Yesenia , Fong Chunki , Kapadia Shashi , Davis La , Smith Melinda , Mateu-Gelabert Pedro , Marks Kristen , Marks Kristen 
Published: December 2021

Abstract

Background
To achieve hepatitis C virus (HCV) elimination, treatment programs need to be developed to engage, treat, and cure people who inject drugs (PWID).

Methods
We present final data from the Accessible Care Trial for curing HCV in PWID. The randomized clinical trial compared on-site, low-threshold HCV treatment with care-coordination at a NYC syringe service program (Accessible Care) with facilitated referral to local providers through a patient navigation program (Usual Care). Eligible participants were HCV RNA+ and had injected drugs in the past 90 days. Participants were randomized 1:1 to the Accessible Care or Usual Care arm. The primary endpoint was achievement of sustained virologic response (SVR12) within 12 months of enrollment. Secondary endpoints examined rates HCV care cascade step completion from referral to clinician, attending clinical visit, baseline lab testing, treatment initiation, and cure.

Results
Among the 572 participants screened, 167 met eligibility criteria and were enrolled, with two excluded post-randomization (N=165). Demographics were similar with a median age of 41 years; 22% women; 59% Hispanic and 5% non-Hispanic black. At baseline, 84% of participants had injected drugs in the past 30 days with those averaging 22 injections/month, 70% were receiving either methadone or buprenorphine, 57% were recently homeless, 7% were HIV+, and 11% were HCV treatment experienced. In the intention-to-treat analysis, 55/82 (67.1%) of the Accessible Care arm and 19/83 (22.9%) of the Usual Care arm achieved SVR12 (p&lt; 0.001). The SVR12 rates of those starting therapy were 55/64 (85.9%) and 19/22 (86.3%) in the two arms (p=0.96). Loss to follow-up (12.2% and 16.9%, p=0.51) was similar in the two arms. Significantly more participants in the Accessible Care arm achieved all steps in the care cascade with the greatest attrition in the Usual Care arm seen in referral to clinician and attending clinical visit.

Conclusion
Among HCV RNA+ PWID significantly higher rates of cure were achieved using the Accessible Care model focused on low-threshold, destigmatized, flexible HCV care compared to facilitated referral. To achieve HCV elimination, expansion of treatment programs specifically geared toward engaging PWID is paramount.

Disclosures
Benjamin Eckhardt, MD, MS, Gilead Sciences (Grant/Research Support) Shashi Kapadia, MD, Gilead Sciences Inc (Grant/Research Support) Kristen Marks, MD, Gilead Sciences (Grant/Research Support)
930. Clinically Significant CMV Infections in Patients with Lymphoma or Multiple Myeloma
Authors: Sassine Joseph , Khawaja Fareed , Shank Brandon R , Lovell Alexandra , Lee Jenessa , DiPippo Adam , Rausch Caitlin R , Spallone Amy , Heredia Ella Ariza , Chemaly Roy F 
Published: December 2021

Abstract

Background
Clinically significant CMV infections (CS-CMVi) among patients with lymphoma and multiple myeloma (MM) have not been clearly defined, especially considering the new cancer therapies that have revolutionized cancer outcomes of these patients. This study aims at describing clinical outcomes of CS-CMVi in this patient population and identify risk factors for CS-CMVi.

Methods
This is a single-center, cohort study of all patients with lymphoma and MM who developed CS-CMVi between January 2017 and October 2020. Data was collected from the electronic medical records. CMV outcomes were defined according to the standardized definitions for clinical trials. Data was analyzed on IBM® SPSS version 26 using a logistic regression model for multivariate analysis.

Results
We identified 84 patients; 60 (71%) had lymphoma and 24 (29%) had MM (Table 1). CMV end organ disease was diagnosed in 53 (63%) patients as the initial CMV episode and the most common site was the lungs (68%). In our cohort, 25 (30%) patients had autologous HCT and 14 (17%) had CAR T cells infusions prior to CS-CMVi. Recurrent CS-CMVi occurred in 16 (19%) patients (Table 2). A 100-day all-cause mortality was 55%, at a median of 76 days (range 3 -1330 days) after the initial episode of CS-CMVi. CMV related mortality was 11% amongst patients with end organ disease. In multivariate analysis, female gender was associated with a higher risk of CMV end organ disease (OR 3.42, 95% CI 1.14-10.3) and MM with a lower risk of CMV end organ disease compared to lymphoma (OR 0.27, 95% CI 0.07-0.97) (Table 3). Interestingly, 16 (19%) patients received letermovir as secondary prophylaxis for a median of 94 days (range 5 to 339 days) and only 1 patient had recurrent CS-CMVi while on letermovir.

Conclusion
CS-CMVi, particularly end organ disease, are not uncommon among patients with lymphoma or MM. Routine CMV surveillance and the use of letermovir for secondary prophylaxis in this patient population should be evaluated in further studies.

Disclosures
Fareed Khawaja, MBBS, Eurofins Viracor (Research Grant or Support) Ella Ariza Heredia, MD, Merck (Grant/Research Support) Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma (Consultant, Grant/Research Support)Chimerix (Consultant, Grant/Research Support)Clinigen (Consultant)Genentech (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Merck (Consultant, Grant/Research Support)Molecular Partners (Consultant, Advisor or Review Panel member)Novartis (Grant/Research Support)Oxford Immunotec (Consultant, Grant/Research Support)Partner Therapeutics (Consultant)Pulmotec (Consultant, Grant/Research Support)Shire/Takeda (Consultant, Grant/Research Support)Viracor (Grant/Research Support)Xenex (Grant/Research Support)
936. Risk Factors and Clinical Outcomes for Extended-Spectrum Beta-Lactamase Producing Enterobacterales Blood Stream Infections in Patients with Hematologic Malignancies
Authors: Lefemine Amanda , Meredith Jacqueline , Hammer Katie , Kachur Ekaterina , He Jiaxian , Speight Carly C , shahid zainab 
Published: December 2021

Abstract

Background
Hematologic malignancy patients have high rates of antibiotic exposure, and increasing resistance is a major concern, particularly with extended-spectrum beta lactamases (ESBL) in Enterobacterales blood stream infections (BSIs). Identifying risk factors for ESBL-producing Enterobacterales (ESBL-E) BSIs may facilitate faster appropriate antibiotic use and decrease mortality.

Methods
This was a retrospective study of patients with hematologic malignancies and Escherichia coli or Klebsiella spp. bacteremia admitted to Carolinas Medical Center in Charlotte, NC from January 2010 through September 2020. The primary objective was to compare 30-day mortality rates for patients with ESBL-E BSIs to those with non-ESBL-E BSIs. Fisher’s exact or Mann-Whitney U tests were used for primary and secondary clinical outcomes as appropriate. Risk factors associated with 30-day mortality and ESBL production were assessed as secondary objectives using logistic regression models.

Results
A total of 28 patients with ESBL-E BSIs and 60 patients with non-ESBL-E BSIs were included. The 30-day mortality rate with ESBL-E BSIs was 25% compared to 15% with non-ESBL-E BSIs (P = .373). In-hospital mortality, 30-day infection recurrence, intensive care unit (ICU) admission, and length of stay after culture were not significantly different. However, time to optimal therapy was longer in the ESBL-E group (median 42.3 vs 1.9 hr; P &lt; .001). Multivariate logistic regression analysis showed an association of 30-day mortality with ICU admission (OR 16.7; 95% CI, 3.56-78.4; P &lt; .001) and longer time to optimal therapy (OR 1.03; 95% CI, 1.0-1.05; P = .026). Prior ESBL-positive culture was associated with ESBL-E BSI in the univariate logistic regression (OR 9.83; 95% CI, 1.05-92.56; P = .046). Additionally, prolonged neutropenia (OR 3.05; 95% CI, 1.01-9.23; P = .049) and prior intravenous antibiotic use (OR 2.96; 95% CI, 0.96-9.09; P = .059) were associated with ESBL-E BSI in the multivariate analysis.

Conclusion
Significantly longer time to optimal therapy was seen in ESBL-E BSIs and was associated with mortality in patients with hematologic malignancies. The identified ESBL risk factors create an opportunity to decrease delay in optimal therapy through risk stratification during initial antibiotic selection.

Disclosures
Ekaterina Kachur, PharmD, BCOP, Bristol Myers Squibb (Advisor or Review Panel member)Genentech (Employee)Glaxosmithkline (Advisor or Review Panel member)Kyowa Kirin (Advisor or Review Panel member)