1298. Acquisition of TDF-Susceptible HIV Despite High Level Adherence to Daily TDF/FTC PrEP as Measured by Dried Blood Spot (DBS) and Segmental Hair Analysis: A Case Report

Abstract Background Pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (TFV) disoproxil fumarate (FTC/TDF) is highly protective against HIV infection. We report the second case of acquisition of TDF-susceptible HIV despite high adherence to PrEP, confirmed by drug level testing. Methods PrEP adherence was assessed by measuring FTC/TDF metabolites in dried blood spots (DBS) and FTC/TFV concentrations in segments of scalp hair. Genotypic and phenotypic resistance were evaluated. HIV partner services (PS) and HIV sequences reported to HIV surveillance with a genetic distance ≤1.5% (by HIV-Trace) identified likely transmission partners. Results A 21-year-old Latino man presented 13 months after PrEP initiation. He was HIV negative by rapid HIV antibody (Ab) and HIV RNA pooling (detection limit ~40 copies/mL) at PrEP initiation and at months 3, 6, and 10. At the 13-month visit, he was asymptomatic and his rapid HIV Ab was negative. Five days later, his HIV RNA was reported as positive (559 copies/mL). He was notified of the result, linked to care and immediately started antiretroviral treatment (ART), at which point his RNA was 1544 copies/mL and his HIV Ab test was positive. The HIV genotype had M184V, L74V and K103N mutations and phenotypic susceptibility to TDF. TFV/FTC levels by LC-MS/MS measured in 1 cm segments of hair collected at ART initiation indicated consistently high PrEP adherence in each of the preceding 6 months. TFV-diphosphate and FTC-triphosphate levels in DBS collected 2 days after ART initiation were 1012 fmol/punch and 0.266 pmol/punch, confirming high adherence over the preceding 6 weeks. Between PrEP initiation and HIV acquisition, he had 1 episode of urethral chlamydia and three episodes of urethral gonorrhea. The likely transmission partner, named during PS, had no history of viral suppression in HIV surveillance and harbored the same resistance mutations, with a genetic distance between the two patients of 0.66%. The partner was re-linked to care and had a current HIV RNA of 15,130 copies/mL. Conclusion Acquisition of TDF-susceptible HIV infection can occur despite high PrEP adherence. Quarterly HIV and STD screening of patients on PrEP, combined with prompt linkage to care and PS for those diagnosed with HIV, facilitates early diagnosis and prevents further transmission of HIV. Disclosures S. E. Cohen, Gilead: Investigator in PrEP study for which Gilead donated drug, donated study drug and paid for drug testing during the PrEP demo project, of which I was a co-PI (the study has ended). S. Lee, Viiv Healthcare: Investigator, Research grant. Gilead Sciences: Investigator, Research grant. P. Anderson, Gilead: Consultant and Investigator, funds were paid to the institution for contract work and grant support and Research support. D. Havlir, Gilead: Investigator, Gilead Sciences provides antiretroviral therapy for a NIH funded study that she is conducting and Research support.

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866. Adherence to F/TDF for PrEP in Dried Blood Spots and HIV Infection Rates: A Pooled Analysis of Global PrEP Studies

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1061 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S524-S525

Author(s):

Albert Liu ◽

Robert Grant ◽

Raphael J Landovitz ◽

...

Keyword(s):

Hiv Infection ◽

Confidence Intervals ◽

Pooled Analysis ◽

Incidence Rates ◽

Hiv Incidence ◽

Research Support ◽

High Background ◽

Material Support ◽

Support Research ◽

Research Grant

Abstract Background The use of daily F/TDF for HIV pre-exposure prophylaxis (PrEP) substantially reduces HIV acquisition. Dried blood spot (DBS) tenofovir-diphosphate (TFV-DP) levels reflect TDF use over the past 6-8 weeks, providing an objective measure of adherence in people taking PrEP. Methods In a pooled analysis of 19 PrEP demonstration projects and clinical studies, 6,613 participants had at least one TFV-DP measurement in DBS and followed for at least 48 weeks and up to 96 weeks. We used a piecewise linear mixed-effects model to plot the least-square means with corresponding 95% confidence intervals (CI) of TFV-DP for adherence over time, and Poisson regressions to calculate HIV incidence rates (IR) by level of weighted average of TFV-DP. Results Of 6,613 participants, median age was 30 years (interquartile range 24−38), 5,449 (82%) were cisgender men, 806 (12%) were cisgender women, and 349 (5%) were transgender (316 transgender women, 2 transgender men, 31 unspecified). Adherence based on TFV-DP in DBS was consistently higher among participants who did not acquire HIV compared to those who did (Figure). Among all participants, 21%, 14%, 36%, and 29% has DBS consistent with taking < 2, 2−3, 4−6, and ≥7 tablets of F/TDF PrEP per week (Table). Sixty-nine participants acquired HIV, with a median PrEP exposure of 0.82 years and an overall HIV IR (95% CI) of 1.16 (0.92, 1.47) per 100 person years. There was a strong association between adherence and HIV incidence [among individuals who took < 2, 2−3, 4−6, and ≥7 tablets/week, the HIV IRs (95% CI) were 5.20 (4.03, 6.71), 0.38 (0.12, 1.18), 0.28 (0.12, 0.61), and 0.06 (0.01, 0.39), respectively. Overall IR (95% CI) of HIV infection among cisgender men was 1.25 (0.98, 1.60) per 100 patient-years. Four cisgender women and 2 transgender participants acquired HIV, corresponding to IRs (95% CI) of 0.71 (0.27, 1.90) and 0.63 (0.16, 2.53). Adherence by TFV-DP in DBS for F/TDF users who acquired HIV compared to those who did not. Note: ‘x’ on the Figure represents visit week when a new HIV infection was detected. HIV incidence rates (95% confidence intervals) by adherence to PrEP measured by level of TFV-DP in DBS up to 96 weeks after PrEP Initiation Conclusion This diverse, multi-national pooled analysis of F/TDF PrEP use provides the largest assessment to date of the adherence-HIV incidence relationship in people taking F/TDF for PrEP. The results suggest a high background HIV incidence in the pooled cohort and high efficacy in those adherent to PrEP. These findings support ongoing efforts to increase PrEP use among people who would benefit. Disclosures Albert Liu, MD, MPH, Gilead Sciences (Individual(s) Involved: Self): Gilead has donated study drug for studies I have led., Grant/Research Support, Other Financial or Material Support, Research Grant or Support; IAS-USA (Individual(s) Involved: Self): Honorarium for manuscript writing, Other Financial or Material Support; Viiv Healthcare (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support Raphael J. Landovitz, MD, MSc, Gilead Sciences (Individual(s) Involved: Self): Consultant; Janssen (Individual(s) Involved: Self): Consultant; Merck Inc (Individual(s) Involved: Self): Consultant; Roche (Individual(s) Involved: Self): Consultant Jared Baeten, MD, PHD, Gilead Sciences Inc. (Employee, Shareholder) David Magnuson, PharmD, Gilead Sciences Inc (Employee, Shareholder) Moupali Das, MD, Gilead Sciences Inc. (Employee, Shareholder) Christoph C. Carter, MD, Gilead Sciences Inc. (Employee, Shareholder) Li Tao, MD, PhD, Gilead Sciences Inc (Employee, Shareholder)

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Changes in Clinical Context for Kaposi's Sarcoma and Non-Hodgkin Lymphoma Among People With HIV Infection in the United States

Journal of Clinical Oncology ◽

10.1200/jco.2016.67.6999 ◽

2016 ◽

Vol 34 (27) ◽

pp. 3276-3283 ◽

Cited By ~ 17

Author(s):

Elizabeth L. Yanik ◽

Chad J. Achenbach ◽

Satish Gopal ◽

Anna E. Coghill ◽

Stephen R. Cole ◽

...

Keyword(s):

United States ◽

Hiv Infection ◽

Hodgkin Lymphoma ◽

The United States ◽

Incidence Rates ◽

Cd4 Counts ◽

Hiv Rna ◽

Non Hodgkin Lymphoma ◽

Art Initiation ◽

Over Time

Purpose The biology of HIV-associated cancers may differ depending on immunologic and virologic context during development. Therefore, an understanding of the burden of Kaposi's sarcoma (KS) and non-Hodgkin lymphoma (NHL) relative to antiretroviral therapy (ART), virologic suppression, and CD4 count is important. Patients and Methods KS and NHL diagnoses during 1996 to 2011 were identified among patients with HIV infection in eight clinical cohorts in the United States. Among patients in routine HIV clinical care, the proportion of cases in categories of ART use, HIV RNA, and CD4 count at diagnosis were described across calendar time. Person-time and incidence rates were calculated for each category. Results We identified 466 patients with KS and 258 with NHL. In recent years, KS was more frequently diagnosed after ART initiation (55% in 1996 to 2001 v 76% in 2007 to 2011; P-trend = .02). The proportion of patients with NHL who received ART was higher but stable over time (83% overall; P-trend = .81). An increasing proportion of KS and NHL occurred at higher CD4 counts (P < .05 for KS and NHL) and with undetectable HIV RNA (P < .05 for KS and NHL). In recent years, more person-time was contributed by patients who received ART, had high CD4 counts and had undetectable HIV RNA, whereas incidence rates in these same categories remained stable or declined. Conclusion Over time, KS and NHL occurred at higher CD4 counts and lower HIV RNA values, and KS occurred more frequently after ART initiation. These changes were driven by an increasing proportion of patients with HIV who received effective ART, had higher CD4 counts, and had suppressed HIV RNA and not by increases in cancer risk within these subgroups. An improved understanding of HIV-associated cancer pathogenesis and outcomes in the context of successful ART is therefore important.

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Novel Criteria for Diagnosing Acute and Early HIV Infection in a Multi-National Study of Early Antiretroviral Therapy Initiation

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1893 ◽

2020 ◽

Author(s):

Trevor A Crowell ◽

Justin Ritz ◽

Robert W Coombs ◽

Lu Zheng ◽

Joseph J Eron ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Hiv Infection ◽

Chronic Infection ◽

National Study ◽

Future Research ◽

Hiv Rna ◽

Art Initiation ◽

Therapy Initiation ◽

New Criteria ◽

Positive Results

Abstract Background Antiretroviral therapy (ART) initiation during acute and early HIV infection (AEHI) limits HIV reservoir formation and may facilitate post-ART control but is logistically challenging. We evaluated the performance of new AEHI diagnostic criteria from a multi-national prospective study of ART initiation during AEHI. Methods ACTG 5354 enrolled adults at 30 sites in the Americas, Africa, and Asia who met any one of six criteria based on combinations of results of HIV RNA, HIV antibody, Western blot or Geenius assay, and/or the signal-to-cutoff (S/CO) ratio of the ARCHITECT HIV Combo Ag/Ab CMIA or GS HIV COMBO Ag/Ab EIA. HIV infection and Fiebig stage were subsequently confirmed by centralized testing. Results From 2017-2019, 195 participants were enrolled with median age 27 (interquartile range 23-39) years. Thirty (15.4%) were female. ART was started by 171 (87.7%) on the day of enrollment and 24 (12.3%) the next day. AEHI was confirmed in 188 (96.4%) participants after centralized testing, four (2.0%) participants were retrospectively found to have chronic infection, and three (1.5%) found not to have HIV discontinued ART and were withdrawn. Retrospectively, a nonreactive or indeterminate HIV antibody on the Geenius assay combined with ARCHITECT S/CO ≥10 correctly identified 99 of 122 (81.2%) Fiebig II-IV AEHI cases with no false-positive results. Conclusions Novel AEHI criteria incorporating ARCHITECT S/CO into diagnostic algorithms facilitated rapid and efficient ART initiation without waiting for an HIV RNA result. These new criteria may facilitate AEHI diagnosis, staging, and immediate ART initiation in future research studies and clinical practice.

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PrEP uptake, persistence, adherence, and effect of retrospective drug level feedback on PrEP adherence among young women in southern Africa: Results from HPTN 082, a randomized controlled trial

PLoS Medicine ◽

10.1371/journal.pmed.1003670 ◽

2021 ◽

Vol 18 (6) ◽

pp. e1003670

Author(s):

Connie Celum ◽

Sybil Hosek ◽

Mandisa Tsholwana ◽

Sheetal Kassim ◽

Shorai Mukaka ◽

...

Keyword(s):

Young Women ◽

Controlled Trial ◽

Drug Level ◽

Dried Blood Spots ◽

African Women ◽

Hiv Incidence ◽

Resistance Mutations ◽

Adherence Support ◽

High Adherence ◽

Missed Visits

Background Pre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence support strategies for African AGYW were studied in an implementation study. Methods and findings HIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV–negative women ages 16–25 were offered PrEP and followed for 12 months; women who accepted were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP ≥700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio [OR] of 0.92; 95% confidence interval [CI] 0.55, 1.34; p = 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of incentives on adherence, and there was limited awareness of PrEP at the time the study was conducted. Conclusions In this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population. Trial registration ClinicalTrials.gov NCT02732730.

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The Effect of Antiretroviral Therapy on IL-6, IL-1β, TNF-α, IFN-γ Levels and their Relationship with HIV-RNA and CD4+ T Cells in HIV Patients

Current HIV Research ◽

10.2174/1570162x18666200712174642 ◽

2020 ◽

Vol 18 (5) ◽

pp. 354-361

Author(s):

Gülay Okay ◽

Meliha Meric Koc ◽

Eray Metin Guler ◽

Ayşegül Yabaci ◽

Abdürrahim Kocyigit ◽

...

Keyword(s):

T Cell ◽

Hiv Infection ◽

Cell Count ◽

Cd4 T Cell ◽

Positive Correlation ◽

Hiv Rna ◽

Tnf Α ◽

Cytokine Levels ◽

Ifn Γ ◽

Cd4 T Cell Count

Background: Serum cytokine levels over the course of HIV infection usually increase with immunosuppression and decrease after antiretroviral treatment (ART). Objectives: The aim of the study is to compare cytokine levels between HIV-infected patients (HIP) and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine levels. Methods: The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and sex-matched healthy controls. We measured levels of IL-6, IL-1β, TNF-α, and IFN-γ in serum samples of HIP at the beginning and at month 6 of ART and in controls. Results: The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the study subjects (n=26). IL-6, IL-1β, and TNF-α levels were significantly higher in both ART-naive (p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002). There was a positive correlation between the CD4+T cell count and serum concentration of IFN- γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA level(r=-0.412, p<0.001), the serum IL-1β, IL-6, and TNF-α concentrations showed a positive correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p<0.00). Conclusions: Although serum concentrations of IL-6, IL-1β and TNF-α showed a significant decrease after ART, they were still significantly higher than the controls. IFN-γ responded differently to ART compared to the other cytokines, indicating that it may play a distinct and important role in the pathogenesis of HIV infection.

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57. Evaluating the Utility of a Penicillin Allergy Reconciliation Program within an Infectious Diseases Consult Population in a Community Health System

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.102 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S49-S50

Author(s):

Bruce M Jones ◽

Emily Plauche ◽

Susan E Smith ◽

Christopher M Bland

Keyword(s):

Infectious Diseases ◽

Health System ◽

Community Health ◽

Intervention Program ◽

Primary Outcome ◽

Panel Member ◽

Penicillin Allergy ◽

Secondary Outcome ◽

Research Support ◽

Research Grant

Abstract Background Penicillin allergy reconciliation is an important aspect of antimicrobial stewardship with ~10% of the population reporting a penicillin allergy. Our facility utilizes a Penicillin Allergy Reconciliation Program (PARP) led by an Infectious Diseases (ID) Pharmacist and pharmacy students to identify patients with penicillin allergies to reconcile and intervene when necessary. Information is collected by interview, electronic medical record (EMR) review, prescription outpatient fill history. This study evaluated reconciliations with and without a PARP in patients in a community health system. Methods This was a retrospective study that compared reconciliations performed on adult patients admitted at least once in 2019 with a self-reported penicillin allergy and ID physician consult at a hospital with a PARP (Institution 1) and one without a formal evaluation and intervention program (Institution 2) within the same community health system with same ID physicians. The primary outcome was documented reconciliation of a patient’s penicillin allergy during an inpatient visit in 2019. Reconciliation was defined as an edit or clarification (updating the severity, reaction, or comments section, as well as deleting) to a patient’s penicillin allergy in the EMR. The secondary outcome evaluated the percentage of total and ID consult patients with a penicillin allergy. Results There were 245 patients who met criteria and were included in the study, 113 from Institution 1 and 132 from Institution 2. For the primary outcome, there were 82 (72.6%) reconciliations at Institution 1 and 15 (11.4%) reconciliations at Institution 2 (p < 0.001). Interventions at Institution 1 and 2 resulted in 74 EMR updates and 8 removals and 14 EMR updates and 1 removal, respectively. Reconciliation was performed on the same visit as the ID consult in 59/82 patients (72%) at Institution 1 and 11/15 patients (73.3%) at Institution 2. All reconciliations at Institution 2 were made by pharmacist (10) or nurses (5). For the secondary outcome, 10.9% of patients with an ID consult and 12.6% of all patients admitted in 2019 had a penicillin allergy (p=0.027). Conclusion A PARP led by an ID pharmacist and students was an effective method to perform penicillin allergy reconciliations, even in the presence of active ID consultation. Disclosures Bruce M. Jones, PharmD, BCPS, ALK-Abello (Research Grant or Support)Allergan/Abbvie (Speaker’s Bureau) Christopher M. Bland, PharMD, FCCP, FIDSA, BCPS, ALK Abello, Inc. (Grant/Research Support)Biomerieux (Consultant)Merck (Consultant, Grant/Research Support, Advisor or Review Panel member, Speaker’s Bureau)Tetraphase (Speaker’s Bureau)

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AB1346-HPR REAL-WORLD EFFECTIVENESS AND PERCEIVED USEFULNESS OF SYMPTOM CHECKERS IN RHEUMATOLOGY: INTERIM REPORT FROM THE PROSPECTIVE MULTICENTER BETTER STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1604 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1961.1-1961

Author(s):

J. Knitza ◽

J. Mohn ◽

C. Bergmann ◽

E. Kampylafka ◽

M. Hagen ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Real World ◽

Search Engines ◽

Correct Diagnosis ◽

Perceived Usefulness ◽

Symptom Duration ◽

Research Support ◽

Link Type ◽

The Mean ◽

Research Grant

Background:Symptom checkers (SC) promise to reduce diagnostic delay, misdiagnosis and effectively guide patients through healthcare systems. They are increasingly used, however little evidence exists about their real-life effectiveness.Objectives:The aim of this study was to evaluate the diagnostic accuracy, usage time, usability and perceived usefulness of two promising SC, ADA (www.ada.com) and Rheport (www.rheport.de). Furthermore, symptom duration and previous symptom checking was recorded.Methods:Cross-sectional interim clinical data from the first of three recruiting centers from the prospective, real-world, multicenter bETTeR-study (DKRS DRKS00017642) was used. Patients newly presenting to a secondary rheumatology outpatient clinic between September and December 2019 completed the ADA and Rheport SC. The time and answers were recorded and compared to the patient’s actual diagnosis. ADA provides up to 5 disease suggestions, Rheport calculates a risk score for rheumatic musculoskeletal diseases (RMDs) (≥1=RMD). For both SC the sensitivity, specificity was calculated regarding RMDs. Furthermore, patients completed a survey evaluating the SC usability using the system usability scale (SUS), perceived usefulness, previous symptom checking and symptom duration.Results:Of the 129 consecutive patients approached, 97 agreed to participate. 38% (37/97) of the presenting patients presented with an RMD (Figure 1). Mean symptom duration was 146 weeks and a mean number of 10 physician contacts occurred previously, to evaluate current symptoms. 56% (54/96) had previously checked their symptoms on the internet using search engines, spending a mean of 6 hours. Rheport showed a sensitivity of 49% (18/37) and specificity of 58% (35/60) concerning RMDs. ADA’s top 1 and top 5 disease suggestions concerning RMD showed a sensitivity of 43% (16/37) and 54% (20/37) and a specificity of 58% (35/60) and 52% (31/60), respectively. ADA listed the correct diagnosis of the patients with RMDs first or within the first 5 disease suggestions in 19% (7/37) and 30% (11/37), respectively. The average perceived usefulness for checking symptoms using ADA, internet search engines and Rheport was 3.0, 3.5 and 3.1 on a visual analog scale from 1-5 (5=very useful). 61% (59/96) and 64% (61/96) would recommend using ADA and Rheport, respectively. The mean SUS score of ADA and Rheport was 72/100 and 73/100. The mean usage time for ADA and Rheport was 8 and 9 minutes, respectively.Conclusion:This is the first prospective, real-world, multicenter study evaluating the diagnostic accuracy and other features of two currently used SC in rheumatology. These interim results suggest that diagnostic accuracy is limited, however SC are well accepted among patients and in some cases, correct diagnosis can be provided out of the pocket within few minutes, saving valuable time.Figure:Acknowledgments:This study was supported by an unrestricted research grant from Novartis.Disclosure of Interests:Johannes Knitza Grant/research support from: Research Grant: Novartis, Jacob Mohn: None declared, Christina Bergmann: None declared, Eleni Kampylafka Speakers bureau: Novartis, BMS, Janssen, Melanie Hagen: None declared, Daniela Bohr: None declared, Elizabeth Araujo Speakers bureau: Novartis, Lilly, Abbott, Matthias Englbrecht Grant/research support from: Roche Pharma, Chugai Pharma Europe, Consultant of: AbbVie, Roche Pharma, RheumaDatenRhePort GbR, Speakers bureau: AbbVie, Celgene, Chugai Pharma Europe, Lilly, Mundipharma, Novartis, Pfizer, Roche Pharma, UCB, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Timo Meinderink: None declared, Wolfgang Vorbrüggen: None declared, Cay-Benedict von der Decken: None declared, Stefan Kleinert Shareholder of: Morphosys, Grant/research support from: Novartis, Consultant of: Novartis, Speakers bureau: Abbvie, Novartis, Celgene, Roche, Chugai, Janssen, Andreas Ramming Grant/research support from: Pfizer, Novartis, Consultant of: Boehringer Ingelheim, Novartis, Gilead, Pfizer, Speakers bureau: Boehringer Ingelheim, Roche, Janssen, Jörg Distler Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Peter Bartz-Bazzanella: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Martin Welcker Grant/research support from: Abbvie, Novartis, UCB, Hexal, BMS, Lilly, Roche, Celgene, Sanofi, Consultant of: Abbvie, Actelion, Aescu, Amgen, Celgene, Hexal, Janssen, Medac, Novartis, Pfizer, Sanofi, UCB, Speakers bureau: Abbvie, Aescu, Amgen, Biogen, Berlin Chemie, Celgene, GSK, Hexal, Mylan, Novartis, Pfizer, UCB

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FRI0052 INFLUENCE OF RHEUMATOID ARTHRITIS ON THE CLINICAL AND BIOLOGICAL PROFILE OF TYPE-2 DIABETES MELLITUS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5408 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 601.2-602

Author(s):

J. Avouac ◽

M. Elhai ◽

M. Forien ◽

J. Sellam ◽

F. Eymard ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Insulin Requirement ◽

Multivariate Logistic Regression ◽

Biological Profile ◽

Research Support ◽

Insulin Resistant ◽

Research Grant

Background:Type-2 diabetes and rheumatoid arthritis (RA) are two chronic diseases characterized by tissue inflammation and insulin resistance. To date, no data have evaluated the influence of RA-induced joint and systemic inflammation on the course of type-2 diabetes.Objectives:To study the impact of RA on type-2 diabetesMethods:Observational, multicenter, cross-sectional usual-care study, including 7 rheumatology centers. This study included over a 24-month period consecutive patients with type-2 diabetes and RA, fulfilling the 2010 ACR / EULAR criteria, and diabetic controls with osteoarthritis (OA). The following data were collected: demographics, disease activity and severity indices, current treatment for RA and diabetes, history and complications of diabetes. A systematic blood test was performed, assessing inflammatory (CRP levels) and metabolic (fasting glycemia and insulin levels, HbA1c) parameters. The HOMA2%B (insulin secretion) and HOMA2%S (tissue insulin sensitivity) indices (HOMA calculator, © Diabetes Trials Unit, University of Oxford) were used to assess insulin resistance. Ra and OA patients were compared using parametric tests after adjusting for age and BMI. A multivariate logistic regression was performed ti identify factors independently associated with insulin resistance.Results:We included 122 RA patients (74% women, mean age 64+/-11 years, mean disease duration 15+/-11 11 years, 75% with positive ACPA antibodies and 64% with erosive disease) and 54 controls with OA. 64% of RA patients were treated with oral corticosteroids <10 mg/day, 65% received methotrexate and 53% received targeted biological therapies.The characteristics of type-2 diabetes in the 54 OA patients corresponded to severe insulin-resistant diabetes: age> 65 years, high BMI> 30 kg/m2, mean HbA1c 7.3%+/-11 1.3%, 30% of insulin requirement, high frequency of other cardiovascular risk factors, macroangiopathy found in almost half of patients and biological criteria of insulin resistance (elevation of HOMA2%B and decrease of HOMA2%S).RA patients with type-2 diabetes had a younger age (64+/-11 years vs. 68+/-12 years, p=0.031) and lower BMI (27.7+/-11 5.5 vs. 31.5+/-11 6.3, p<0.001). These patients also had severe diabetes (HbA1c 7.0%+/-11 1.2%, 29% of insulin requirement, 43% of macroangiopathy) with an insulin resistance profile identical to OA controls. After adjusting for age and BMI, RA patients had a significantly increased insulin secretion compared to OA patients (HOMA2%B: 83.1+/-11 65.2 vs. 49.3+/-11 25.7, p=0.023) as well as a significant reduction of insulin sensitivity (HOMA2%S: 61.1+/-11 31.6 vs. 92.9+/-11 68.1, p=0.016). This insulin resistance was associated with the inflammatory activity of RA, with a negative correlation between the HOMA2%S and the DAS28 (r=-0.28, p=0.027). The multivariate logistic regression confirmed the independent association between the HOMA2%S index and DAS28 (OR: 3.93, 95% CI 1.02-15.06), as well as high blood pressure (OR: 1.29, 95% CI 0.33-1.99 CI).Conclusion:RA patients with type-2 diabetes displayed severe, poorly controlled diabetes, highlighting the burden of comorbidities associated with RA. The clinical-biological profile of diabetic RA patients was severe insulin-resistant diabetes, with a biological profile of insulin resistance linked to the inflammatory activity of the disease. These findings may have therapeutic implications, with the potential targeting of insulin resistance through the treatment of joint and systemic inflammation.Acknowledgments:Société Française de Rhumatologie (research grant)Bristol Myers Squibb (research grant)Disclosure of Interests:Jérôme Avouac Grant/research support from: Pfizer, Bristol Myers Squibb, Consultant of: Sanofi, Bristol Myers Squibb, Abbvie, Boerhinger, Nordic Pharma, Speakers bureau: Sanofi, Bristol Myers Squibb Abbvie, MSD, Pfizer, Nordic Pharma, Muriel ELHAI: None declared, Marine Forien: None declared, Jérémie SELLAM: None declared, Florent Eymard Consultant of: Regenlab, Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Frédéric Banal: None declared, Joel Daminano: None declared, Philippe Dieudé: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi

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1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1290 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S582-S583

Author(s):

Eleni Karantoni ◽

Yiqi Su ◽

Anat Stern ◽

Phaedon D Zavras ◽

Sergio Giralt ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

T Cell ◽

Panel Member ◽

Multivariable Model ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Advisory Boards ◽

Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

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913. Distribution of Respiratory Viral Pathogens in Infants Across Different Clinical Settings from December 2019 to April 2020

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1101 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S491-S492

Author(s):

Zaid Haddadin ◽

Danielle A Rankin ◽

loren lipworth ◽

Jon Fryzek ◽

Mina Suh ◽

...

Keyword(s):

Clinical Setting ◽

Respiratory Viruses ◽

Clinical Settings ◽

Research Support ◽

Viral Pathogens ◽

Abrupt Decrease ◽

Nasal Swabs ◽

Viral Testing ◽

Support Research ◽

Research Grant

Abstract Background Acute respiratory infections (ARI) are a major cause of morbidity and mortality in young children, with viral pathogens being the most common etiologies. However, due to limited and inconsistent clinical diagnostic viral testing in the outpatient (OP) setting compared to the inpatient (IP) setting, the actual burden and distribution of viral pathogens across these clinical settings remain largely underreported. We aimed to evaluate the frequency of common respiratory viruses in medically attended ARI in infants. Methods We conducted a prospective viral surveillance study in Davidson County, TN. Eligible infants under one year presenting with fever and/or respiratory symptoms were enrolled from OP, emergency department (ED), or IP settings. Nasal swabs were collected and tested for common viral pathogens using Luminex® NxTAG Respiratory Pathogen Panel and for SARS-CoV-2 using Luminex® NxTAG CoV extended panel. Results From 12/16/2019 to 4/30/2020, 364 infants were enrolled, and 361 (99%) had nasal swabs collected and tested. Of those, 295 (82%) had at least one virus detected; rhinovirus/enterovirus (RV/EV) [124 (42%)], respiratory syncytial virus (RSV) [101 (32%)], and influenza (flu) [44 (15%)] were the three most common pathogens detected. No samples tested positive for SARS-CoV-2. Overall, the mean age was 6.1 months, 50% were male, 45% White and 27% Hispanic. Figure 1 shows the total number of PCR viral testing results by month. RSV was the most frequent virus detected in the IP (63%) and ED (37%) settings, while RV/EV was the most common in the OP setting (Figure 2). Figure 3 displays viral seasonality by clinical setting, showing an abrupt decrease in virus-positive cases following the implementation of a stay-at-home order on March 23, 2020 in Nashville, TN. Distribution of Respiratory Viruses in Different Settings Distribution of Respiratory Viruses in Different Settings by Season Conclusion Most medical encounters in infants are due to viral pathogens, with RSV, RV/EV, and flu being the most common. However, distributions differed by clinical setting, with RSV being the most frequently detected in the IP and ED settings, and second to RV/EV in the OP setting. Continued active viral ARI surveillance in various clinical settings is warranted. Preventative measures such as vaccines and infection control measures deserve study to reduce viral ARI burden. Disclosures Zaid Haddadin, MD, CDC (Grant/Research Support, Research Grant or Support)Quidel Corporation (Grant/Research Support, Research Grant or Support)sanofi pasteur (Grant/Research Support, Research Grant or Support) Danielle A. Rankin, MPH, CIC, Sanofi Pasteur (Grant/Research Support, Research Grant or Support) Jon Fryzek, PhD, MPH, EpidStrategies (Employee) Mina Suh, MPH, International Health, EpidStrategies (Employee) Donald S. Shepard, PhD, Sanofi Pasteur (Grant/Research Support) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support)

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