bluuebunny/crossref_metadata_2025 huggingface dataset:
343. T-cell Subsets Associated with Diabetes in Veterans with and without HIV
Authors: Bailin Samuel , McGinnis Kathleen , McDonnell Wyatt J , So-Armah Kaku , Wellons Melissa , Doyle Margaret , Mallal Simon , Justice Amy , Freiberg Matthew , Koethe John
Published: October 2019

Background

Depletion of naïve CD4+ T cells and elevated adaptive immune activation are hallmarks of HIV infection. Higher proportions of memory CD4+ T cells are associated with prevalent diabetes in the general population, but few studies of persons with HIV (PWH) exist.

Methods

We analyzed data from 1532 PWH and 836 uninfected veterans in the longitudinal Veterans Aging Cohort Study (VACS), which archived peripheral mononuclear cells from these veterans between 2005 and 2007. We used flow cytometry to phenotype CD4+ and CD8+ T cells, including naïve, activated CD38+, senescent CD57+, total memory, and memory subsets. Prevalent diabetes (at blood collection) was identified in the VA electronic medical record using random glucose, hemoglobin A1c, ICD-9 codes, and medication. Cases were validated by two-physician chart review. We used multivariate logistic regression models adjusted for age, gender, body mass index, race/ethnicity, unhealthy alcohol use, hepatitis C, CMV status, and viral suppression stratified by HIV status to identify T-cell subsets associated with diabetes in PWH and uninfected.

Results

The cohort was 95% male, 68% African-American, and 22% diabetic. Higher CD4+CD45RO+ memory T cells were associated with prevalent diabetes in the uninfected and in PWH (P = 0.03 and P = 0.07, respectively; Figure A). Among subsets, diabetes was associated with higher transitional memory CD4+ T cells in the uninfected (P = 0.01), but higher central memory cells (P = 0.02) and lower effector memory cells (P = 0.04) in PWH. T effector memory RA+ cells were not associated with diabetes. Lower senescent CD4+CD57+ T cells were associated with diabetes in both PWH and uninfected (P = 0.03 and P = 0.04, respectively; Figure B), but results for naïve CD8+ T cells diverged: diabetes was associated with higher naïve CD8+cells in PWH but lower in uninfected (P = 0.01 and P < 0.01, respectively; Figure C). We assessed interaction by HIV status in a pooled model, which was only significant for the naïve CD8+ T cells (P = 0.01).

Conclusion

The adaptive immune profile associated with prevalent diabetes was similar by HIV status and characterized by a shift in CD4+ T cells from senescent to memory phenotypes, suggesting that chronic immune activation contributes to the higher risk of diabetes in PWH.

Disclosures

All authors: No reported disclosures.
345. Acute Onset Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic State in Patients Taking Integrase Strand Transfer Inhibitors
Authors: Ntem-Mensah Afua Duker , Millman Nina , Jakharia Niyati , Theppote Amanda , Toeque Mona-Gekanju , Riedel David J
Published: October 2019

Background

A few case reports have noted uncontrolled hyperglycemia in patients switched to dolutegravir. Several cohort studies have found increased weight gain among patients treated with integrase inhibitors (INSTI). We present clinical observations among 3 patients admitted to hospital for diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) while receiving INSTIs for the management of HIV.

Methods

Case 1: A 44-year-old man with HIV and dyslipidemia presented with altered mental status and lethargy. A fingerstick glucose was >600 mg/dL. Chemistries revealed glucose of 1,600 mg/dL and an elevated β-hydroxybutyrate. HbA1c was 12.4%. His antiretroviral regimen consisted of cEVG/TAF/FTC for the last 3 years. Previous HbA1c levels were 5.7% and 6.2% (Figure 1). Case 2: A 55-year-old woman with HIV, hypertension, dyslipidemia, and obesity presented with polyuria and polydipsia. The blood glucose level was >1,200 mg/dL with an anion gap >30 and HbA1c of 15%. Previous HbA1c levels ranged between 5.6 and 5.8% (Figure 2). She had been taking ABC/FTC/DTG for 2 years.

Case 3: A 64 yo man with a history of HIV, hypertension, and obesity presented with polyuria and polydipsia. The blood glucose level was 1,152 mg/dL with no anion gap and HbA1c of 13.4%. Six months before, he had been switched from a c/DRV- based ART regimen to ABC/FTC/DTG. Previous HbA1c levels ranged between 5.8% and 6.2% (Figure 3).

Results

Discussion: In the first 2 patients, the presentation with acute onset DKA occurred more than a year after being on an INSTI-based regimen; however, the latter patient presented with HHS within 6 months of being switched to an INSTI-containing regimen. The mechanism of action of INSTIs causing weight gain or an association with hyperglycemia is still under investigation.

Conclusion

Although the temporal onset of DKA and HHS while receiving INSTIs was not precise, the possible association of INSTIs and their direct effects on insulin resistance and diabetes warrant additional attention from post-market data. Meanwhile, providers should monitor INSTI-treated patients closely, especially those with features of metabolic syndrome.

Disclosures

All authors: No reported disclosures.
346. Factors Associated with Hypertension in Young Adults with Perinatally-Acquired HIV Infection: a Case–Control Study
Authors: O’Neil Patrick , Ryscavage Patrick , Stafford Kristen A
Published: October 2019

Background

The incidence of systemic hypertension (HTN) among perinatally-HIV-infected (PHIV) patients appears to increase as they enter adulthood. Among non-perinatally HIV-infected adults both traditional and HIV-associated risk factors have been found to contribute to HTN. Whether these same factors contribute to HTN in PHIV is unknown. The purpose of this study was to determine the socio-demographic, clinical, virologic, and immunologic factors associated with HTN among a cohort of PHIV adolescents and young adults, aged ≥18 years.

Methods

We conducted a case–control study among a population of 160 PHIV adults with and without HTN who were receiving care at the University of Maryland and aged 18–35 years as of December 31, 2017. Covariates assessed included traditional risk factors such as age, family history of HTN, and smoking, as well as HIV- and antiretroviral-associated covariates.

Results

We identified 49 HTN cases (30.6%) and 111 (69.4%) controls. There were no significant differences in the odds of most traditional (age, gender, race, family history of HTN, tobacco, alcohol, and/or other drug use) or HIV-associated (CD4 nadir <100 cells/mm3, individual ART exposure, ART interruption) risk factors among PHIV adults with HTN compared with those with no diagnosis of HTN. Cases had lower odds of a history of treatment with lopinavir/ritonavir (LPV/r). Cases had 3.7 (95% CI 1.11, 12.56) times the odds of a prior diagnosis of chronic kidney disease (CKD) compared with controls after controlling for CD4 nadir and ARV treatment history.

Conclusion

The results of this study suggest that most traditional and HIV-related risk factors do not appear to increase the odds of having HTN in this PHIV cohort. However, HTN among PHIV may be driven in part by CKD, and a focus on the prevention and early management of CKD in this group may be necessary to prevent the development of HTN. Additionally, there may be as yet unidentified risk factors for HTN among PHIV which require further exploration. Given the large and growing population of PHIV entering adulthood worldwide, it is imperative to explore risk factors for and effects of HTN in large, diverse PHIV populations.

Disclosures

All authors: No reported disclosures.
349. Implementation of a Multidisciplinary HIV-Pulmonary Clinic
Authors: Sellers Subhashini A , Durr Amy , Sanghani Aarti , Pierce Jonah , Little Hannah D , Farel Claire E
Published: October 2019

Background

Among people with HIV (PWH), pulmonary comorbiditiees are a leading cause of morbidity and mortality. As PWH live a near-normal lifespan with ART, the focus has shifted from opportunistic infections to chronic disease. This includes chronic obstructive pulmonary disease (COPD) and lung cancer, for which PWH with and without concomitant tobacco use are at high risk. We sought to improve access to and quality of pulmonary care for PWH by instituting a pulmonary clinic co-located within a Ryan White-funded HIV clinic in the Southeastern United States.

Methods

A pulmonologist with expertise in lung disease in PWH began seeing patients one half-day twice monthly beginning in 2017. Longitudinal demographic, clinical, and appointment information was collected on each patient.

Results

Fifty patients were referred to the HIV-Pulmonary clinic. Of the 32 patients seen for an initial visit, the mean age was 55, 63% were male, and all were on ART. The majority were current (52%) or prior smokers (31%) with a mean pack-year history of 42. Over 40% of the patients had a COPD diagnosis and 25% had no prior pulmonary diagnosis. The majority of patients had not engaged in pulmonary care within the past year, as 63% had never seen a pulmonologist and another 28% did not follow-up with a prior provider. After the first visit, 69% either followed up or had a pending follow-up. Of the 17 current smokers, all were offered assistance with smoking cessation and 59% engaged. Of the 10 patients who were eligible for lung cancer screening (LCS) by current guidelines, all engaged in shared decision making and 40% pursued annual screening CT scans.

Conclusion

Chronic pulmonary diseases are increasing relevant comorbidity in PWH on ART. Our HIV-pulmonary clinic demonstrates the utility and feasibility of integration of sub-specialty consultative care in comprehensive care of PWH. By introducing a general pulmonary clinic within the existing infrastructure of the HIV clinic at our institution, we were able to engage PWH with and at risk for lung disease in longitudinal care to prevent, detect, and treat pulmonary disease. Future goals of this interdisciplinary design include increased compliance with current COPD treatment guidelines and LCS, improved rates of smoking cessation, and continued collaboration between the ID and pulmonary providers.

Disclosures

All authors: No reported disclosures.
355. Barriers for Hepatitis C Elimination in HIV/HCV Coinfected Patients
Authors: Espinoza Joe , Vigil Karen J , Barnett Ben
Published: October 2019

Background

Approximately 30% of people living with HIV are co-infected with Hepatitis C virus (HCV). HIV/HCV coinfected patients have faster progression to liver fibrosis, cirrhosis, and increased mortality, compared with monoinfected patients. Therefore, treatment in this population is a priority. The objective of this study was to develop an active program to reach HIV/HCV co-infected patients, with the goal to eliminate Hepatitis C in our local HIV clinic.

Methods

Beginning in December 2016, our clinic received State funds to support open access to treat HIV/HCV patients with direct-acting antivirals (DAA). From December 2016 to May 2018, the process was based on primarily on physician referrals to treat HIV/HCV patients at our clinic, without an active intervention, and 50 patients were treated. Our active intervention during the second part was based on the identification of all untreated HIV/HCV patients and contacting them directly, to link them to care.

Results

A total of 462 HIV/HCV co-infected patients were identified who qualified for the state-sponsored treatment program. From June 1, 2018 to July 31, 2018, only 7 patients were linked to care and started on DAA. The four main identified reasons for not getting DAA therapy were: no show up to the clinic appointments, poor adherence to their HIV antiretroviral treatment, use of drugs and not able to be reached (figure). Although drug use was listed as one of the main reasons for not receiving DAA therapy, it was not the defining reason for most patients. A majority of the patients had more than one obstacle preventing them from coming in to be treated.

Conclusion

Wide availability of DAA and open access to treatment is not enough to eliminate HIV/HCV co-infection. Innovative outreach processes with the active participation of key stakeholders are needed in order to eliminate this viral infection.

Disclosures

All authors: No reported disclosures.
357. Hepatitis C (HCV) Testing and Diagnosis and Their Relationship to Sexually Transmitted Infection (STI) Screening and New Infections in an HIV+ Men Who Have Sex with Men (MSM) Outpatient Cohort
Authors: Cooper Joseph D , Beil Robert S , Zingman Barry S
Published: October 2019

Background

Assess HCV prevalence, screening, new infections and reinfections and their relationship to other STI screening and diagnosis in HIV+ MSM at an urban center.

Methods

Retrospective review of HCV and STI testing and diagnosis among HIV+ MSM with ≥1 visit January 1, 2016–October 31, 2018 at Montefiore’s Center for Positive Living and Medical Group outpatient sites. Demographics from local databases, clinical data from EPIC and chart review on select cases.

Results

876 HIV+ MSM, median age 42, 80% virally suppressed. 850 (98.2%) had known HCV status. 36/850 (4.2%) HCV Antibody (Ab)+ at any point: 23 (2.7%) at baseline (6 dual MSM/IDU), 13 (1.5%) newly Ab+ (0 dual risk). 4/36 (11.1%) HCV RNA+: 1 of baseline Ab+, 3 in newly Ab+’s. Among new Ab+’s, 7 asymptomatic, 6 symptomatic, most commonly high liver tests. 3/13 (15.4%) were persistently viremic requiring therapy. 614/827 (74.2%) HCV Ab-’s were retested ≥1, 260 (31.4%) >1x – average retesting interval 13 months. Among 36 HCV Ab+’s, 0 had reinfection. Testing and new STIs by HCV status is in Table 1. 2/13 (15.4%) with new HCV were not tested for gonorrhea or chlamydia (G/C) at any site. Acute syphilis was more common in new HCV+’s than HCV-’s (P =.002). HCV rescreening was higher in those tested for extragenital (EG) G/C vs. those not tested (Table 2), but up to 18.8% were not HCV retested despite EG testing done. 304/876 (34.7%) were ≤35 years of age. Testing and positive results for all four STIs were greater in those ≤35 (Table 3). Non-Hispanic (NH)-Black was the largest race/ethnicity and had the highest rate of new STI’s except pharyngeal chlamydia, rectal gonorrhea and acute syphilis (Table 4).

Conclusion

We found significant risk of HCV among HIV+ MSM in our cohort, with a prevalence of 2.7% and a 34-month incidence of 1.5%, with no reinfections. HIV+/HCV Ab- MSM were frequently retested for HCV but missed opportunities among sexually active individuals lead to delayed diagnoses of acute infection. Unexplained elevation of liver tests in sexually active HIV+ MSM should prompt immediate HCV testing, and more HCV Ab testing is indicated as part of STI screening in this group. Awareness should be raised about risk of acute HCV with new syphilis, and there is room to improve EG G/C testing.

Disclosures

All authors: No reported disclosures.
358. HIV Infection and the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Virus (HBV) Co-infection: a Propensity Score-matched Cohort Study
Authors: Lui Grace , Yip Terry , Yuen Becky , Sze Alex , Hui Yee-tak , Tse Yee-Kit , Wong Vincent , Wong Grace
Published: October 2019

Background

There is a paucity of data to show whether HIV infection would affect the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection.

Methods

A territory-wide cohort study was performed to determine the risk of HCC in patients with HBV with and without HIV co-infection. All patients with HBV/HIV co-infection and HBV mono-infection treated with antiviral therapy in public hospitals in Hong Kong from 2000 to 2017 were identified from an electronic database. Patients with hepatitis C virus (HCV) infection, HCC diagnosed within six months, or follow-up less than 6 months were excluded. The primary outcome was HCC. A propensity score (PS) for each patient was defined as the conditional probability of having HIV infection given the baseline characteristics (including age, sex, cirrhosis, bilirubin, alanine transaminase/ALT, platelet, albumin, and prothrombin time). HBV/HIV-co-infected and HBV-monoinfected patients were matched in a 1:5 ratio by PS matching. Weighted Fine-Gray subdistribution hazards model was estimated, where the variables included were HIV status and ALT as the other important co-variates were well matched.

Results

A total of 822 HBV/HIV-coinfected and 53,974 HBV-monoinfected patients were identified, and 692 and 38,102 were included for PS matching (Figure 1). Six hundred and three HBV/HIV-coinfected and 2,380 HBV-monoinfected patients were included in the final analysis. Among this cohort, 85% were male, mean (± standard deviation) age was 42 ± 12 years, and 4.5% had cirrhosis at baseline. At a median follow-up of 5.8 (interquartile range 2.6–9.6) years, 7 (1.2%) and 75 (3.2%) HBV/HIV-coinfected and HBV-monoinfected patients developed HCC, respectively. Weighted Fine-Gray model showed that HIV infection was associated with a lower risk of HCC (subdistribution hazard ratio 0.39, 95% confidence interval 0.16–0.94, P = 0.036) (Figure 2).

Conclusion

HIV/HBV co-infected patients had lower risk of HCC compared with antiviral therapy-treated HBV-monoinfected patients. This observation can be explained by a lower threshold, in terms of severity of liver disease, to start antiviral treatment in HBV/HIV-coinfected compared with HBV-monoinfected patients.

Disclosures

All authors: No reported disclosures.
361. Residual Lamivudine-Resistant Hepatitis B Virus Detected on Next-Generation Sequencing of Treatment-Experienced HIV Patients Failing Antiretrovirals
Authors: Schwem Brian , Francisco Christian , Dungca Nina Theresa , Arevalo Geraldine , Penalosa-Ramos Christine , Lim Jodor , Salvana Edsel Maurice T
Published: October 2019

Background

Hepatitis B is highly prevalent in the Philippines, with 17% of the population infected. With the fastest-growing HIV epidemic in the Asia-Pacific, 12% of HIV patients are HBsAg reactive. With the use of lamivudine and tenofovir-based antiretrovirals (ARVs), hepatitis B virus (HBV) treatment in co-infected HIV patients is not usually an issue. However, there is a potential to develop HBV resistance when patients are switched off tenofovir when antiretroviral resistance develops. With high rates of acquired K65R tenofovir resistance, the potential for inadvertently causing re-emergence of lamivudine-resistant HBV is present. We report two HIV patients with residual whole-genome HBV with lamivudine and telbivudine resistance mutations.

Methods

As part of a surveillance study on acquired drug resistance in the Philippines, samples with an HIV viral load >1,000 copies underwent Sanger sequencing of RT and PR for genotyping and HIV drug-resistance testing. Near-whole-genome next-generation sequencing (NGS) for HIV using Illumina HiSeq was also performed on these samples.

Results

Two patients had coincidental whole-genome amplification of HBV on NGS (Table 1). HBV serology for both showed reactive anti-HBsAg and non-reactive HBsAg and Anti-HBc. The two HBV samples were genotype A and were resistant to lamivudine and telbivudine, with intermediate resistance to entecavir.

Conclusion

Residual HBV may be present in patients on ARVs. Antibody responses for HBV serology may not be very reliable in highly immunosuppressed patients. The potential of lamivudine-resistant HBV to emerge when HIV patients are shifted off tenofovir due to resistance in patients should be considered when deciding on second-line ARVs.

Disclosures

All authors: No reported disclosures.
362. Hepatitis C Virus (HCV) Co-Infection in Women Living with Human Immunodeficiency Virus (HIV) in Northwest Louisiana
Authors: Mohammed Ethar , Nambiar Puja
Published: October 2019

Background

HIV and HCV infection are emerging global public health problems. People living with untreated HIV infection have higher HCV viral loads and more rapid HCV disease progression with twice the rates of perinatal HCV transmission. Data are lacking in HCV coinfected women living with HIV. Our study reviewed underrepresented minority group of women living with HIV/HCV in Northwestern Louisiana to better understand epidemiology, risk factors and access to care among this cohort.

Methods

Women with HIV/HCV coinfection aged 18–70 years who presented to an academic medical center between November 2011 and November 2018 were included for analysis. A retrospective chart review was conducted. Data were collected and analyzed on demographics (age, race), risk factors (sexual history, drug use), HIV (viral load, CD4 count, antiretroviral treatment (ART)), and HCV (viral load level and antibody, genotype, alanine transaminase, liver fibrosis, liver cirrhosis, referral, and treatment).

Results

A total of 41 patients met our inclusion criteria. The mean age was 52 years. Of these HIV/ HCV coinfected women, 27 (66%) were African American and 14 (34%) Caucasian. 18 (44%) had history of Injection drug use. Thirty-nine out of 41 (95%) were linked to HIV care and on antiretroviral therapy with 36 (88%) with CD4 count >200. Twenty-three out of 41 (56%) was referred for HCV treatment but only 11 (26%) co-infected patients received treatment for HCV.

Conclusion

In this cohort of HCV/HIV coinfected women, only 26% of the women received HCV treatment. Some of the barriers include access to providers, linkage to care and behavioral and socioeconomic factors. The lack of timely appropriate HCV care in this underserved high-risk population is alarming especially in the current era of highly effective direct-acting antiviral therapy for HCV. Despite improved HIV care, further work needs to focus on optimizing HCV screening, linkage and treatment uptake in order to overcome multiple barriers to HCV elimination in this patient population.

Disclosures

All authors: No reported disclosures.
366. Severe Neurologic Impairment Persists Despite Potent ART in HIV Encephalopathy
Authors: Cutler Riley , Trentman Sarah , Jandarov Roman , Brown Jennifer , Robertson Kevin , Fichtenbaum Carl
Published: October 2019

Background

Approximately 4–8% of the 1.1 million HIV patients in the United States have or will be diagnosed with HIV encephalopathy or HIV associated dementia (HAD). There are no published studies of the long-term outcomes of HAD treated with potent antiretroviral therapy (ART). We hypothesize that more than 60% of individuals diagnosed with HAD will have persistent neurocognitive impairment despite the successful use of potent ART and fewer than 20% will be employed.

Methods

This is a cross-sectional prospective and retrospective study of outcomes in individuals previously diagnosed with HAD. We identified all individuals with the diagnosis of dementia and HIV at the UC Infectious Diseases Center (IDC). For those who matched the 1993 CDC HAD definition, we collected medical, neurocognitive, and functional information. We attempted to contact all individuals alive and still in the IDC practice (N = 26) to perform a validated battery of neuropsychological tests. We excluded individuals with HIV-associated neurocognitive disease that developed after treatment with ART.

Results

We confirmed 39 diagnoses of HAD out of 137 records reviewed. The median CD4 count at the time of diagnosis of HAD was 47 cells/mm3 with a median viral load of 211,475 copies/mL. The median length of follow-up after diagnosis of HAD was 72 months (range 1–166 months). Potent ART was prescribed to all individuals, with 67.5% reaching consistent undetectable viral loads (< 200 copies/mL, occasional blips allowed). Persistent neurologic deficits were noted in 32.5%, while 60% had persistent cognitive deficits. Psychiatric disturbances were present in 72.5%. Only 2.5% reported any employment. To date, 28% have died. Ten participants have undergone formal neurocognitive testing to date (N = 26 available). The median overall summary score (total Z score) was -1.17 (range 0.08, -1.95) and median global deficit (GDS) score was 1.48 (range 0, 2.92).

Conclusion

HIV-associated dementia results in substantial morbidity and mortality despite potent antiretroviral therapy. Prospective neurocognitive assessment documents significant impairments in most individuals. HIV-associated dementia will require additional strategies to mitigate the profound impact on the quality of life and longevity.

Disclosures

All authors: No reported disclosures.
376. Effect of Parasitic Infections on Gut Epithelial Barrier and Immune Activation among Foreign-Born HIV-infected Patients
Authors: Reimer-McAtee Melissa , Somasunderam Anoma , Huan Xu Teena , Arduino Roberto , Serpa Jose , Mejia Rojelio , Utay Netanya S
Published: October 2019

Background

Strongyloides stercoralis often causes an asymptomatic infection despite continuous autoinfection for the lifetime of the host. Both HIV and recurrent enteric parasitic infections cause gut damage and increased microbial translocation, but little is known about the effects of co-infection. We aimed to evaluate changes in immune activation, mucosal damage, and microbial translocation in people with HIV-1 (PWH) and parasite co-infection.

Methods

In this pilot prospective cohort study, we enrolled foreign-born PWH on suppressive antiretroviral therapy (ART) in an ambulatory clinic in Houston, Texas. We evaluated serum Strongyloides IgG using ELISA with an S. stercoralis-specific recombinant protein. Intestinal fatty acid-binding protein (I-FABP), soluble CD14 (sCD14), sCD163, IL-6, and sTNFRII were analyzed as markers of enterocyte turnover, inflammation, and immune activation. Non-parametric tests were used for analysis.

Results

52 participants born in 14 countries were enrolled February–March 2019. Median CD4 count was 464/uL [95% CI 315–598]. Fourteen (27%) were positive for Strongyloides IgG. Strongyloides IgG levels correlated positively with sCD14 levels [r=0.36; P = 0.008]. Strongyloides+ participants had significantly higher sCD14 levels compared with Strongyloides− participants [1.67 vs. 1.48 μg/mL, P = 0.031]. Among the Strongyloides+ participants, Strongyloides IgG levels correlated with sCD163 levels [r=0.65, P = 0.026]. There were no difference in the other biomarkers. Logistical regression analysis showed that predictors of Strongyloides+ include absolute eosinophil count (AEC) (OR 1.45 for every 100 increase of AEC [95% CI: 1.02, 2.15; P = 0.047]). CD4 count, number of years living in the United States, country of origin, and years from HIV diagnosis were not associated with test positivity.

Conclusion

Strongyloides co-infection is common among foreign-born PWH and may contribute to chronic monocyte/macrophage activation, a predictor of morbidity and mortality in PWH. Future directions include stool PCR confirmation of these infections, continued enrollment, and follow-up assays 6 months after treatment of Strongyloides to determine the impact on inflammation and risk of co-morbidities.

Disclosures

All authors: No reported disclosures.
377. Diagnostic Yield of Bone Marrow Aspiration and Biopsy in Human Immunodeficiency Virus Patients with Fever and/or Cytopenia
Authors: Egge Stephanie , Malus Mathew , Osorio Ariel , Mansour Richard , Master Samip , Stevenson Joel Chandranesan Andrew
Published: October 2019

Background

Human Immunodeficiency Virus (HIV) patients are at increased risk of opportunistic infections and malignancies. Evaluation for the etiology of fever and/or cytopenia with conventional means such as cultures and serology can remain negative. Bone marrow aspiration or biopsy (BMAB) has the advantage of diagnosing disseminated infections, hematological abnormalities and oncological malignancies in HIV patients.

Methods

We performed a retrospective descriptive study of HIV patients with fever and/ or cytopenia who underwent Bone marrow aspiration or biopsy (BMAB). Patients with a diagnosis of HIV, 18 years and older who underwent BMAB in University Health (UH) Hospital or in UH clinics from January 2012 to February 2018 were included.

Results

There were a total of 42 patients who underwent Bone Marrow Aspiration or Biopsy. The median age was 41.5 years. Twenty-eight patients were Male and 14 were female. Preexisting Hematological malignancy was present in 10 patients at the time of BMAB. Average CD4 count at the time of BMAB was 92. 8 patients were compliant with ART and 12 patients were compliant with clinic appointments. White Blood Cell (WBC) count below 4.4 cells / L was present in 30 patients at the time of BMAB. Disseminated Mycobacterium Avium Complex infection (2 patients),Disseminated Histoplasmosis (2 patients), Disseminated Cryptococcus (1 patient) and Parvovirus B19 (based on Immunohistochemistry, 1 patient) were diagnosed from BMAB. CD4 count of these 6 patients range from 0 to 12 at the time of BMAB. All 6 patients presented to the hospital with fever for evaluation. Average WBC count, Hemoglobin and platelet count in these patients are 4.1 cells / liter, 8.7 g/dL and 74.8 k/micro liter, respectively. All 6 patients were non compliant to HIV medications and clinic appointments.

Conclusion

Since the advent of Anti Retroviral drugs with excellent efficacy and early diagnosis of HIV patients, incidence of disseminated fungal and mycobacterial infections have decreased in the United States. But patients with low CD4 count and cytopenias warrant a Bone Marrow aspiration or Biopsy to make a clear and early diagnosis.

Disclosures

All authors: No reported disclosures.
383. Rheumatic Disease Patients Have More Culture Negative Prosthetic Joint Infections: Are There Clinical Differences?
Authors: Kapadia Milan , Miller Andy O , Nocon Allina , Sculco Peter , Goodman Susan M
Published: October 2019

Background

Rheumatic disease (RD) patients are at increased risk for prosthetic joint infections (PJI), however, diagnosis is challenging because active RD may mimic joint infection. We aimed to assess the incidence of culture-negative (CN) PJI in a population of RD and osteoarthritic (OA) PJI using an institutional PJI registry. Baseline clinical differences between CN-RD and culture-positive (CP)-RD as well as the relationship of culture negativity to survivorship of the prosthesis were also evaluated.

Methods

A retrospective cohort of hip and knee PJIs, from 2009 to 2016, were identified by ICD codes, and confirmed by chart review. RD cases were identified by ICD code and use of RD-specific medications. CN cases were defined as PJIs with no evidence of microbial growth in intraoperative cultures. Demographics, medications, microbiology, surgical therapy and outcome were abstracted. Baseline characteristics were evaluated using Fisher’s exact and Chi-Square tests. Kaplan–Meier estimates were used to calculate survivorship.

Results

803 PJI cases were identified including 36 RD (33 rheumatoid arthritis and 3 systemic lupus erythematosus) and 771 OA. A higher proportion of RD PJI were CN (N = 10, 27%) vs. OA PJI (N = 109, 14%, P = 0.02). Fewer CN-RD cases met PJI histopathology criteria compared with CN-OA, (P = 0.08). On average, RD-CN were younger than OA-CN (59 vs 69, P = 0.01), but no different than RD-CP cases. One year survivorship of CN-OA and CN-RD were 87% and 66%, respectively and 47% for CP-RD. Comparing CN-RD vs. CP-RD, no difference was observed in age, smoking, diabetes, or Charlson comorbidities, but a trend toward higher prevalence of prior PJI in the CN-RD group. Clinically, no differences were found in surgical treatment (P = 0.92) or use of biologics and DMARDs (P = 0.12) between CN and CP RD patients.

Conclusion

RD PJIs are more likely to be culture-negative than OA PJIs. Prior PJI, histopathology and better outcomes suggest biologic differences that should be explored further.

Disclosures

All authors: No reported disclosures.
389. Risk Factors and Outcomes of Patients with Infectious Complications After Surgical Treatment of Blount Disease
Authors: Polistico Jordan , Polistico Sarah , Dhar Sorabh , Bhargava Ashish
Published: October 2019

Background

Blount disease (idiopathic tibia vara) is an uncommon pediatric growth disorder characterized by unequal endochondral ossification of the medial aspect of the proximal tibial growth plate. Management of Blount’s disease involves performing osteotomy for improved outcomes. The objective of the study was to assess risk factors for infection, microbiology, and outcomes in patients following surgical correction.

Methods

This study is a retrospective case–control study of patients who underwent surgery for Blount disease at Children’s Hospital of Michigan, Detroit from January 1, 2000 to January 31, 2019. Charts from 44 patients who underwent surgical correction were reviewed (22 cases and 22 control patients) and analyzed for basic demographics, surgical risk factors, microbiology, treatment durations, and outcomes.

Results

A total of 44 patients (22 cases and 22 controls) were included. Baseline characteristics, risk factors, and outcomes are shown in Table 1. Significant risk factors for infection included increased obesity and BMI (P < 0.05). The median time to infection from index surgery was 12.5 days, with 11 (52.4%) of the infections categorized as superficial and 10 (46.6) as deep or organ space. 7 (31.8%) infections were polymicrobial and the common pathogen was Staphylococcus aureus (n = 7, 31.8%) (Table 2). Infected patients had an average of 3.25 incision and drainage procedures, and the average duration of antibiotic therapy was 23 days.

Conclusion

Obesity with an increased BMI was associated with increased risk of infectious complication following the surgical treatment of Blount’s Disease with Staphylococcus aureus, is the most common pathogen.

Disclosures

All authors: No reported disclosures.
391. Septic Arthritis and Acute Hematogenous Osteomyelitis in Children: Disease-Specific Antibiogram and Implications for Treatment
Authors: Mobayed Nisreen O , Schlidt Kevin , Roadman Daniel , Hahn Danita , Huppler Anna R
Published: October 2019

Background

Osteomyelitis and septic arthritis are common pediatric musculoskeletal infections with potential to cause significant morbidity. Empiric antibiotic selection is made prior to the availability of microbiologic data. The aim of this study was to compare the epidemiology of osteoarticular infections (OAI) to antibiotic regimens and local antibiograms.

Methods

A retrospective study was performed on patients aged 6 months to 18 years with a diagnosis of septic arthritis or acute hematogenous osteomyelitis in a large, free-standing children’s hospital between July 2012 and July 2017. Exclusion criteria were chronic osteomyelitis, prior trauma or surgery at the site, noninfectious arthritis, and Lyme arthritis. Data collected from the electronic medical record included demographics, initial and discharge antibiotic therapy, and microbiologic results. Data were compared with the local antibiogram during the same time period.

Results

A total of 207 patients were included: 66 patients <4 years (< 4Y) and 141 patients ≥4 years (≥4Y). Causative pathogens were identified in 70% of patients. Staphylococcus aureus comprised 55% of positive results in children < 4Y and 73% in children ≥4Y. Among S. aureus cultures, 70–76% were methicillin sensitive (MSSA). Overall clindamycin susceptibility was 97%, with all resistant strains detected in children ≥4Y with MSSA. This is strikingly different than the institutional antibiogram showing 79% overall clindamycin sensitivity in S. aureus [82% in MSSA, 72% in methicillin resistant (MRSA)]. Kingella kingae was exclusively identified in children <4Y (21% of positives), which was also the group with the highest rate of culture-negative infection (41%). Intravenous clindamycin alone was the most frequent initial antibiotic regimen, prescribed for 41% of all patients. Initial antibiotic regimens matched organism susceptibilities in 90% of MRSA and 100% of MSSA infections.

Conclusion

Our study revealed high rates of clindamycin-susceptible S. aureus in older children and K. kingae and culture-negative infection in children < 4 years with OAI. Antibiotic susceptibilities differing from our institutional antibiogram suggest that disease-specific antibiograms will aid with empiric treatment decisions.

Disclosures

All authors: No reported disclosures.
396. Aminoglycoside Acute Kidney Injury (AKI) Following the Implantation of Tobramycin Loaded Polymethylmethacrylate (PMMA) Cement and Calcium Sulfate (CaSO4) Beads for the Treatment of Periprosthetic Joint Infection (PJI)
Authors: Vasina Logan , Chinn Raymond , Minuto Joshua
Published: October 2019

Background

Antibiotic loaded bone cement (ALBC) in PMMA, generally with tobramycin and vancomycin (TV) is commonly used for the treatment of PJI. CaSO4 beads, loaded with TV is biodegradable and can be used alone or in combination with PMMA. Identification of AKI following documentation of sustained supra-therapeutic tobramycin levels a patient with chronic PJI treated with ALBC (both PMMA + CaSO4) prompted the development of guidelines to mitigate risk of AKI in patients treated with ALBC. Although AKI may be enhanced with vancomycin, case reports with TV in PMMA implicate tobramycin. We provide data in a cohort of patients treated for PJI using PMMA or PMMA + CaSO4.

Methods

Data were obtained to describe clinical findings. As part of a quality improvement initiative, tobramycin and serum creatinine levels were obtained in eight subsequent patients who received PMMA or PMMA + CaSO4 and clinical guidelines were developed to standardize aminoglycoside dosing and monitoring. Vancomycin levels were not routinely monitored.

Results

Figure 1 describes the clinical course of the index patient. Table 1 lists doses, serum creatinine and tobramycin levels the cohort of PJI patients. All patients treated with PMMA + CaSO4 had tobramycin levels from 3.5 to 8.7 µg/mL on a postoperative day (POD) 1 compared with < 2 µg/mL in patients treated with PMMA alone. All patients’ levels peaked on POD 1.

Conclusion

Patients treated with CaSO4 had higher levels in the early postoperative period compared with patients treated with PMMA. In all patients, serum levels appeared similar after 48 to 72 hours. Our experience suggests the use of CaSO4 + PMMA may have important clinical consequences in patients with decreased clearance and/or those at risk for early postoperative renal impairment. Guidelines developed mitigated this potential complication since we have not identified AKI in subsequent patients undergoing treatment of PJI with ALBC. Features of guidelines included: (1) identification of high-risk patients; (2) a flowsheet to guide dosing recommendations based on low/high risk; (3) routine monitoring of levels on POD 1 with a goal of tobramycin < 2 as a surrogate for toxicity. Pharmacy approved dosing must be incorporated into guidelines of care for patients undergoing arthroplasty where ALBC is used.

Disclosures

All authors: No reported disclosures.
401. Predictors of Treatment Failure for Hip and Knee Prosthetic Joint Infections in the Setting of Prosthesis Removal: A Multi-Center Retrospective Cohort
Authors: Kandel Christopher , Jenkinson Richard , Daneman Nick , Backstein David , Muller Matthew P , Katz Kevin , Sajja Abhilash , Garcia Jeldes Felipe , McGeer Allison
Published: October 2019

Background

Prosthetic hip and knee joint infections (PJIs) are challenging to eradicate despite prosthesis removal and long courses of antibiotics. We aimed to describe the risk factors for PJI treatment failure in a multicenter retrospective cohort.

Methods

A retrospective cohort of individuals who underwent prosthetic joint removal for a PJI at one of five hospitals in Toronto, Ontario, Canada from 2010–2014. Individuals eligible for the cohort were obtained by searching operative listings and PJIs were defined according to the criteria of the Musculoskeletal Infection Society. Treatment failure was defined as recurrent PJI, amputation, death or chronic antibiotic suppression. Potential risk factors for treatment failure were abstracted by chart review and assessed using a Cox proportional hazards model.

Results

533 PJIs were analyzed over a median follow-up duration of 1102 days with 21 surgeons performing more than 5 revision arthroplasties for a PJI. Two-stage procedures were performed in 81% (430/533) and the most common organism was coagulase negative staphylococci (32%). Treatment failure occurred in 28% (150/533) over 1443 patient-years and was caused by a different bacterial species in 53% (56/105). On multivariate analysis the characteristics associated with PJI treatment failure included liver disease (adjusted hazard ratio (aHR) 3.12, 95% confidence interval (95% CI) 2.09–4.66), the presence of a sinus tract (aHR 1.53, 94% CI (1.12–2.10), preceding debridement with prosthesis retention (aHR 1.68, 95% CI 1.13–2.51), a one-stage procedure (aHR 1.72, 95% CI (1.28–2.32), and infection due to Gram-negative bacilli (aHR 1.35, 95% CI 1.04–1.76).

Conclusion

PJI treatment failure remains high despite prosthesis removal and the patient risk factors identified are non-modifiable. Novel treatment paradigms are urgently needed along with efforts to reduce orthopedic surgical site infections.

Disclosures

All authors: No reported disclosures.
403. Clinical Features and Treatment Outcome of Enterobacter Prostethic Joint Infections
Authors: Youssef Dima , Hooshmand Babak , Bhargava Ashish
Published: October 2019

Background

Enterobacter prosthetic joint infections (PJIs) are rare, occurring mainly in elderly people usually with complex medical and surgical history, and their treatment is usually challenging. Aim of this study is to assess the characteristics and outcomes of Enterobacter PJIs.

Methods

A retrospective multi-centric cohort was studied at three hospitals from January 2012 to December 2018. Patients with PJIs were identified using ICD codes. Enterobacter PJIs were then identified through reviewing patients’ electronic medical records.

Results

13 enterobacter PJIs were identified. 9 (69%) were polymicrobial. Mean age of the patients was 61.7 years, and mean BMI was 34.6 kg/m2. 8 patients (62%) were females, and 8 patients (62%) were Caucasians. Infected sites were: Hip in 5 patients (38%%), knee in 5 patients (38%) and ankle in 3 patients (23%) patients. 9 patients (69%) had osteoarthritis, 3 patients (23%) had diabetes mellitus, and 1 patient (8%) had connective tissue diseases requiring steroids. Most patients (11 out of 13) (85%) presented within 1 week of symptoms onset. Presenting clinical features were pain in 9 patients (69%), drainage in 10 patients (77%), purulence in 7 patients (54%), and fever in 5 patients (38%). 11 patients (85%) were managed with debridement, antibiotics and implant retention (DAIR), and 2 patients (15%) with antibiotics alone. Antibiotics used while managing were as follows: Cefepime n = 6, quinolones n = 2, carbapenems n = 4 and aminoglycosides n = 1. Outcome: 4 patients (31%) developed deep surgical site infections (and two of them required implant removal), 5 patients had no events in 12 months of follow-up, 3 patients (23%) had less than 6 months of follow-up, and one patient died in the hospital due to cardiac failure.

Conclusion

In our study, most cases of Enterobacter PJIs were polymicrobial. The success rate in monomicrobial infections was 75% while overall it was noted to be 38%. DAIR was associated with high readmission rates and deep surgical site infections (36%). 18% cases managed with DAIR required implant removal.

Disclosures

All authors: No reported disclosures.
413. Differences in Inflammatory Mechanisms in Pseudomonas aeruginosa and Staphyloccoccus auereus Infections in Cystic Fibrosis
Authors: Phuong Melissa S , Hernandez Rafael E , Sad Subash
Published: October 2019

Background

Chronic bacterial lung infections are the primary cause of morbidity and mortality in cystic fibrosis (CF). The most common CF pathogens, Pseudomonas aeruginosa (P. aeruginosa) or Staphylococcus aureus (S. aureus), are common commensal or environmental organisms that adapt to the CF lung. We sought to investigate whether adaptation from early lung colonizer to chronic pathogen alters the bacterial effects on host inflammation.

Methods

P. aeruginosa (n = 25) and S. aureus (n = 25) isolates from CF patients with early and chronic infections were acquired from Seattle Children’s CF. Environmental (n = 8) and clinical, non-CF P. aeruginosa (n = 8) isolates were obtained from the University of Ottawa. P. aeruginosa reference strain PA14 and PA14 transposon mutants for T3SS and flagellin were used to observe the relationship between cell death and cytokine production. We infected THP-1-derived macrophages (PMA differentiated) in vitro for 3 hours with various MOIs. We subsequently measured cell death of THP-1-derived macrophages using neutral red assay and cytokine production using ELISAs.

Results

Infections with PA14 mutants and non-CF P. aeruginosa isolates demonstrated that rapid cell death of THP-1-derived macrophages caused a reduction in cytokine production relative to strains that did not cause as much cell death. At 10 MOI, early P. aeruginosa isolates from CF patients induced more THP-1-derived macrophage cell death compared with chronic isolates (P < 0.0001). Chronic P. aeruginosa isolates induced greater production of TNF, IL-8, and IL-6 (P < 0.01, P < 0.0001, and P < 0.0001, respectively) compared with early strains. No difference in IL-1β production was observed. When controlling for cell death between the two groups by using heat-killed bacteria, the only difference maintained was in TNF production (P < 0.01). Between early and chronic S. aureus isolates, the one difference observed was greater IL-8 production among early isolates (P < 0.01).

Conclusion

Chronic P. aeruginosa isolates from CF patients induce less cell death but more TNF, IL-8, and IL-6 production compared with early isolates. This suggests that P. aeruginosa producing chronic infections induce inflammatory signals that may contribute to increased morbidity among CF patients.

Disclosures

All authors: No reported disclosures.
417. Cytomegalovirus (CMV) and Sexually Transmitted infections (STIs) During Pregnancy
Authors: Geetha Pinninti Swetha , Van Der Pol Barbara , Daniel Grace , Fowler Karen , Boppana Suresh
Published: October 2019

Background

Congenital cytomegalovirus infection (cCMV) is a leading cause of hearing loss and neurodevelopmental disabilities. Although higher rates of CMV acquisition and reinfections with new virus strains are seen in women with STIs, the significance of CMV-STI co-infections during pregnancy and whether co-infections increase intrauterine transmission of CMV remains unclear. Higher rates of CMV genital shedding were seen in mothers of infants with cCMV compared with those with uninfected infants. The objective of this study was to determine the association between CMV seroprevalence and STIs and whether STIs during pregnancy influences CMV genital shedding.

Methods

Vaginal swabs from a cohort of CMV seropositive women in labor from a multi-center study were analyzed. After DNA extraction from vaginal swabs, PCR was performed for detection of CMV, Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG). The prevalence of STIs in CMV seropositive pregnant women was determined in this cohort and CMV genital shedding rates were compared between groups with and without STIs.

Results

In this cohort, CMV genital shedding in late pregnancy was detectable in 13% (21/160) of women while rates of detection for MG, GC, CT and TV were 3%, 0.6%, 1.2% and 8%, respectively. CMV-STI co-infections were noted in 2.5% (4/160) of women. CMV genital shedding was documented in only one woman with STIs, compared with 12.5% (20/160) without STIs. Among women shedding CMV in the genital tract, CMV viral load levels ranged from 1.1 × 102 IU/mL to 2.2 × 104 IU/mL.

Conclusion

In a cohort of CMV seropositive women, the presence of STIs in late pregnancy did not increase CMV genital shedding. Our preliminary findings suggest CMV shedding is not associated with STIs detected late in pregnancy.

Disclosures

All authors: No reported disclosures.