bluuebunny/crossref_metadata_2025 huggingface dataset:
214. Comparison of Clinical and Laboratory Findings of Human Monocytic Ehrlichiosis (HME) and Human Granulocytic Anaplasmosis (HGA) in Long Island, New York.
Authors: Azab Nancy , Smith Kalie , Spitzer Eric , Weinbaum Fredric I , Marcos Luis
Published: October 2019

Background

Suffolk County reports to the Department of Health the highest absolute number of cases of tick-borne diseases (TBD) for NY State. While Lyme disease and Babesiosis are the most common TBD in this county with more than 600 and 100 cases reported every year, respectively; two other TBD, HME (due to Ehrlichia chaffeensis) and HGA (due to Anaplasma phagocytophilum) are also commonly reported in this county (63 and 37 every year, respectively). There is limited data directly comparing both diseases on acute presentation; the aim of this study was to compare the clinical features, laboratory findings and complications of HME and HGA in the epicenter of TBD in NY State.

Methods

A retrospective study was designed to collect cases with the diagnosis of HME and HGA by using ICD9 or ICD10 codes from 2013 to 2018 at Stony Brook Medicine. Inclusion criteria were patients 18 years or older who had a positive PCR in blood for E. chaffeensis or A. phagocytophilum. Demographics, clinical features, laboratory results, and complications were extracted from patient charts. We used the chi-square test to compare the proportion of symptoms and a two-tailed unpaired student T-test to compare laboratory values.

Results

A total of 40 cases of HME (mean age 67 ± 13) and 27 with HGA (mean age 63 ± 12) met inclusion criteria. Only approximately 50% of cases had a documented history of tick exposure. Clinical presentations were similar in terms of frequency of fever, headache, arthralgia, and myalgia. In contrast, hypotension, confusion, and rash were more common in HME although only the latter was significantly more common. HME patients had significantly greater degrees of leukopenia and thrombocytopenia and elevated AST levels. The majority of patients with HME and HGA were hospitalized >1 day for management of their acute illness (HME, 30/40 and HGA 17/27). Several patients with HME had gastrointestinal (GI) complications including 3 with acute acalculous cholecystitis, 1 with duodenitis, and 1 with acute colitis; 1 patient with HGA had perforated diverticulitis.

Conclusion

Patients with acute HME tend to be more ill than those with acute HGA; however, a substantial proportion of both groups require hospitalization. GI complications were more commonly seen in HME (12.5%) than HGA (3.7%) which deserves further investigation.

Disclosures

All authors: No reported disclosures.
223. Predicting Mortality Among Immunocompromised Patients Who Present With Bloodstream Infection
Authors: Henig Oryan , Rao Krishna , KB Putler Rosemary , Patel Twisha S , Albin Owen , Kaye Keith S
Published: October 2019

Background

The revised definition of sepsis (Sepsis-3) uses Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) to identify patients with sepsis instead of systemic inflammatory response syndrome (SIRS) criteria. Subsequent studies revealed contradictory results pertaining to qSOFA, and limited data are available for immunocompromised patients. The objectives of this study were to (1) evaluate the performance of Sepsis -3 in a cohort of immunocompromised patients with microbiologically-proven sepsis, defined as having received antibiotics and having bloodstream infection (BSI); and (2) to compare its performance in the BSI cohort to its performance in immunocompromised patients who received antibiotics but did not have BSI (Non-BSI cohort).

Methods

Adult patients with hematologic malignancy or solid transplant recipients admitted to Michigan Medicine between 2012–2017 with suspected infection were included based on criteria used in the Sepsis-3 study: having both a body fluid culture and having received intravenous antibiotics. SOFA, qSOFA and SIRS components within 1 day of the index date (culture date or antibiotic date, whichever came first) were extracted from the medical record. For each group, a baseline risk model for mortality was created including age, gender, race, and Charlson comorbidity index. Each score (SOFA ≥ 2, qSOFA ≥ 2, SIRS ≥ 2) was added to the baseline risk model as a dichotomous variable and AUROC values were calculated.

Results

2822 patients with a mean age of 56.8±15.6 were included. 349 (12.4%) had BSI. The most common immune compromising conditions were solid-organ transplantation (47%), lymphoma (21.3%) and acute leukemia (17%). 14% of patients in the BSI cohort died during hospitalization compared with 6.6% in the non-BSI cohort (P < 0.001). For the BSI cohort, when SOFA ≥ 2, qSOFA ≥ 2, SIRS ≥ 2 scores were added to the model, the AUROC values were less than those for the non-BSI cohort (table). The addition of SOFA ≥6 to the baseline risk model produced the highest AUROC values in both the BSI and non-BSI cohorts (figure).

Conclusion

Among immunocompromised patients, an SOFA score ≥6 was the strongest predictor of mortality. Surprisingly, sepsis scores performed better in the non-BSI cohort than in the BSI cohort.

Disclosures

All authors: No reported disclosures.
227. Prevalence, Comorbidities and Expenditures of S. aureus Bacteremia in Liver Transplant Recipients: A 2012–2016 Nationwide Analysis
Authors: Ramakrishna Jahanavi M , Kroner Paul , Helmi Haytham , Libertin Claudia R
Published: October 2019

Background

Bacteremia due to Staphylococcus aureus is a known complication of liver transplantation (LT). Studies have shown that LT recipients are more predisposed to S. aureus infections than other solid-organ transplant patients; however, these studies have been limited in scope and mostly based out of single centers.

Methods

This is a retrospective cohort study using 2012–2016 NIS, the largest public inpatient database in the United States. All patients with ICD9-10CM procedural codes for LT were included. The cohort was stratified into two groups depending on whether they had MSSA or MRSA infection. The odds of inpatient mortality in both groups of patients undergoing LT were determined. The inpatient mortality odds were then compared with those of patients undergoing LT without associated S. aureus infection. Other outcomes included inpatient morbidity, resource utilization, hospital length of stay (LOS), and inflation-adjusted total hospital costs and charges. Multivariate regression analyses were used to adjust for demographic variables and Charlson Comorbidity Index.

Results

A total of 26,415 patients underwent LT in the study period, of which 180 had MSSA and 160 had MRSA infection reported. The mean age was 51.5 years and 35.6% were female. Patients with MSSA and MRSA displayed significantly higher inpatient mortality rates (11.1% and 9.4%, respectively) compared with non-MSSA/MRSA patients (3.4%) who underwent LT (P < 0.01). After adjusting for confounders, patients with MSSA infection displayed higher mortality odds (aOR: 4.45, P < 0.01), while patients with MRSA infection had non-statistically significant higher inpatient mortality odds (aOR: 3.10, P = 0.12) compared with patients without MSSA/MRSA infection. Both MSSA and MRSA cohorts displayed higher mortality odds if the infection resulted in sepsis (aOR: 9.92 and 5.70, respectively; P < 0.01).

Conclusion

There is a direct correlation between S. aureus bacteremia and increased mortality rates and incidence of sepsis and shock in LT recipients. Patients with S. aureus bacteremia spent more days in hospital and had higher cost of healthcare. Preventing and aggressively treating S. aureus infections in the immediate post-LT setting is key to reducing mortality, morbidity and resource utilization in patients undergoing LT.

Disclosures

All authors: No reported disclosures.
231. Microbial cell-free DNA Sequencing to Detect Borrelia burgdorferi DNA in the Plasma of Pediatric Patients with Lyme Disease
Authors: Handel Andrew S , Ho Carine , Hollemon Desiree D , Hong David K , Beneri Christy
Published: October 2019

Background

Diagnosing Lyme disease often involves laboratory evaluation, yet available tests have limitations. Serology remains negative for weeks after infection occurs, and may then remain positive for years. Borrelia burgdorferi blood PCR testing has low sensitivity, rendering it unhelpful. We sought to determine whether an emerging technology, next-generation sequencing (NGS) of microbial cell-free DNA (mcfDNA), can detect B. burgdorferi DNA in the plasma of pediatric patients with erythema migrans (EM).

Methods

Patients aged 1–17 years with a clinically-identified single or multiple EM were enrolled. Two clinical investigators were required to agree on the EM finding, with no evidence of an alternative diagnosis. Subjects were excluded if they previously had Lyme disease, had received antibiotics within 30 days prior to enrollment, or if the rash had resolved before the first blood draw. Three blood samples were taken during the study period: one before antibiotics were administered, then 1–3 weeks and 2–3 months later. At enrollment, plasma was tested for Lyme disease using C6 antibody with reflex to Western Blot and mcfDNA sequencing (Karius, Inc., Redwood City, CA). Briefly, mcfDNA was extracted from plasma and NGS performed. Human reads were removed and remaining sequences were aligned to a curated microbial database. Only mcfDNA testing was performed at follow-up visits.

Results

We enrolled 5 subjects (ages 4–15 years old, median age 4). Four subjects had a single EM and negative Lyme serology. One subject had approximately 20 EMs and positive serology (C6-antibody=7.52 (Positive >1.09), 3/3 IgM, 2/10 IgG). All 14 plasma samples, including five pre- and nine post-antibiotic samples, were negative for B. burgdorferi DNA by mcfDNA sequencing. No other infections, including other tick-borne infections, were detected.

Conclusion

NGS of mcfDNA did not identify B. burgdorferi DNA in the plasma of pediatric patients with active EM rashes. This approach is unlikely to be helpful in diagnosing early localized Lyme disease. This may be because spirochetes are localized to the periphery of the rash in EM and spirochetemia likely occurs at later stages of infection. Follow-up studies are planned to investigate how NGS of mcfDNA performs during early and late disseminated Lyme disease.

Disclosures

All authors: No reported disclosures.
255. Breakthrough Mucormycosis (BT-MCR) on Antifungals Having Mucorales Activity Portrays Worse Prognosis compared with BT-MCR on Mold-Active Antifungals with no Mucorales Activity
Authors: Axell-House Dierdre B , Jiang Ying , Kyvernitakis Andreas , Lewis Russel E , Raad Issam I , Kontoyiannis Dimitrios P
Published: October 2019

Background

BT-MCR is known to develop in the setting of agents having Aspergillus but no Mucorales activity. However, BT-MCR can occur even with the use of antifungals having with Mucorales activity in patients with hematologic malignancies and or stem cell transplant (HM).

Methods

We reviewed the records of HM patients treated for MCR (1994 to 2019) at MD Anderson Cancer Center. We identified patients with BT-MCR on antifungals having Mucorales activity: posaconazole (POSA), isavuconazole (ISA), and amphotericin B (AMB) (group A), and patients with BT-MCR on agents having Aspergillus but no Mucorales activity: voriconazole (VRC), itraconazole (ITZ), echinocandins (group B). BT-MCR was defined as MCR diagnosis (dx) after ≥7days (d) of antifungal use. The primary outcome was 42d mortality after the BT-MCR dx. Chi-square or Fisher’s exact test was used for categorical variables and Wilcoxon rank-sum test used for continuous variables. Cox regression model was used to evaluate the independent variables on outcome.

Results

We identified 11 patients in group A (3 POSA, 5 ISA, 3 AMB) and 81 patients in group B (61 VRC, 13 echinocandins, 7 ITZ). Both groups were not different in terms of age, sex, underlying HM (AML/MDS in 100% vs. 88% in groups A and B, respectively), status of HM (active disease in 82% vs. 67%), prior stem cell transplant (45% vs. 54%) or GvHD (80% vs. 84%), neutropenia at dx (55% vs. 42%), prior receipt of >600 mg of prednisone (45% vs. 41%) or ICU at MCR dx (36% vs. 26%). Similarly, Mucorales species (Rhizopus spp. in 55% vs. 49%) and type of infection (sino-pulmonary in 73% vs. 68%) were no different between the groups. However, both d42 (82% vs. 46%, P = 0.025) and d84 (100% vs. 60%, P = 0.007) mortality was worse in group A. Similarly, median time to death was faster in patients in group A (26d, range 7-80d), vs. group B (42d, range 4–3146d, P = 0.031). Kaplan–Meier analysis showed a similar difference (Figure 1). In multivariate analysis, neutropenia (P = 0.038) and ICU at dx (P = 0.002) were independent factors on day 42d mortality in all 92 patients with prior Mucorales–active antifungals showing a trend associated with poor outcome (P = 0.17).

Conclusion

BT-MCR on agents having Mucorales activity is a marker of poor prognosis in HM patients. Early use of investigational immunotherapy and salvage antifungal chemotherapy studies is needed in that subgroup of patients.

Disclosures

All authors: No reported disclosures.
268. Fungal NGS: Identification of Etiological Agents of Invasive Fungal Infection by High-throughput Sequencing
Authors: Nelsen Donald J , Sinha Rohita , Tyler Aaron J , Westergaard Jordyn , Nutt Jamie , Wissel Mark , Kleiboeker Steve , Altrich Michelle
Published: October 2019

Background

Invasive fungal infections (IFI) cause severe symptoms that affect immunocompromised and transplant patient populations. Antifungal therapies vary depending on the pathogenic species, and delays in diagnosis can lead to graft loss and an increase in morbidity and mortality. Therefore, rapid identification of fungi causing IFI is critical for informing antifungal therapy. Such actionable genus/species information can be obtained quickly via Next-generation Sequencing (NGS). In this study, an NGS assay was developed to identify fungal species responsible for IFI, allowing for selection of effective antifungal therapies.

Methods

Internal transcribed spacer (ITS) regions 1 and 2 were used for fungal identification. Primers were taken from published research and/or designed/modified by assessment in fungal sequence alignments. A DNA sequence database was compiled and a reference-assisted assembly approach utilizing % sequence ID and % coverage was developed for species identification. End-point PCR was conducted on DNA extracted from 19 pathogenic fungal species, and mixed communities (MC) for preliminary sensitivity and inclusivity. Sensitivity was assessed using dilutions of template DNA into the PCR reaction.

Results

NGS data of 14 individual species and 4 MC passed quality control checks. Using only ITS1 and ITS2, species identification was expected for 10 of 14 individuals. We observed species identification in 9 individual samples, and 13 were identified within the top 5 results. All individuals were identified to genus. In MC analyses, combinations of 3, 4, 6, and 10 fungal species resolved 100% of the genera present, but failed to resolve species adequately with only 2 loci evaluated. Unexpectedly, 3 tested Aspergillus spp. were correctly identified with this limited data in both single and MC samples. The lower limit of detection was assessed at 5,000 genomic equivalents/mL of eluate.

Conclusion

The inclusivity and sensitivity demonstrated here of an NGS approach for identification of etiological agents of IFI support this assay’s potential utility as an aid in the treatment of IFI in at-risk patient groups. This assay allows for rapid identification (<4 days) of fungal species to aid clinicians in improving case outcomes.

Disclosures

All authors: No reported disclosures.
274. Impact of Fungal Serologies in the Management of Veteran Patients with Suspected Endemic Mycoses
Authors: Ordaya Eloy E , Drekonja Dimitri M
Published: October 2019

Background

Endemic mycoses are caused by the dimorphic fungi Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidiodes species. Histoplasmosis and blastomycosis are endemic in Minnesota, with travel to coccidioidomycosis endemic areas being common. Diagnosis is challenging, in part due to confusion regarding laboratory testing. In our institution, we have observed that fungal serologies are often ordered when such infections are suspected, but results rarely seem to affect management. We reviewed the impact of serologic testing on the management of a Midwest veteran population.

Methods

Retrospective, observational study of patients with any serologic testing for endemic mycoses performed from January2014 to December 2018 at the Minneapolis VA Health Care System. To focus evaluation on the utility of serologic testing, we excluded patients with fungal antigen testing.

Results

Of 127 patients tested, 62 (49%) had only serologic testing. Patients were predominantly males (95%) with a median age of 66 years (range 27–93). Nineteen (31%) were tested in the hospital and had a median stay of 8 days (range 1–48). Median Charlson score was 4 (range 0–12). Travel to an endemic area for coccidioidomycosis was frequent (27/62: 44%), with Arizona being the most common destination (20/27: 74%). Median illness duration was 30 days (range 1–720). Respiratory symptoms predominated (43/62: 69%), followed by nonspecific (6/62: 10%), neurologic (5/62: 8%), and musculoskeletal (2/62: 3%) symptoms. Five (8%) were asymptomatic. Abnormal imaging was common, with 27/62 (44%) patients having an abnormal chest radiograph (consolidation 15%, nodules 11%, and interstitial pattern 8%), and 44/62 (71%) having abnormal CT findings (nodules 55%, ground glass opacities 18%, and consolidation 15%). Six patients (10%) had positive serology, but antifungals were started only in one case. Fungal serology results impacted management in 19/43 (44%) patients seen in clinic, but in 0/19 tested as inpatients (P < 0.001). The most common action (16/19: 84%) was to cease diagnostic workup (table).

Conclusion

Fungal serologies can be useful in patients evaluated in clinic who present with respiratory symptoms, abnormal imaging, and potential fungal exposure. Testing in hospitalized patients appears to offer little benefit.

Disclosures

All authors: No reported disclosures.
279. Evaluation of β-d-Glucan Utilization in Thailand: Single Academic Center Experience
Authors: Manothummetha Kasama , Reinprayoon Rongpong , Torvorapanit Pattama , Reinprayoon Navaporn , Ratanawongphaibul Kitiya , Chindamporn Ariya , Permpalung Nitipong
Published: October 2019

Background

β-d-glucan (BG) detection was first available in Thailand in 2016 to aid diagnosis of invasive fungal infections (IFIs). Given a paucity of real-world experience of BG use in resource-limited countries, this study was conducted to describe appropriateness of BG testing and sequelae of BG results.

Methods

A retrospective study included all patients with at least 1 BG ordered at King Chulalongkorn Memorial Hospital, Bangkok, Thailand during March 2016 to December 2018. Descriptive statistics were used.

Results

83 patients were tested by BG assay (Fungitell, Associates of Cape Cod, Inc.): 6 with hematopoietic stem cell transplant, 12 with solid-organ transplant, 20 with active cancer receiving chemotherapy, 34 receiving high dose steroids (≥20 mg/day of prednisone for ≥3 weeks) and 11 with other conditions. Seventy-three patients were tested under infectious disease (ID) service’s recommendations. There were 13 and 20 cases of proven and probable IFIs, respectively. Among 13 proven IFIs, there were 11 positive, 1 indeterminate and 1 negative (mucormycosis) BG results. Among 49 cases with positive BG results, 24 were determined to be false-positive results. Median turn-around time for BG results was 16 (IQR: 9–23) days. Due to high turn-around time, only 8 patients were started on antifungal agent(s) and 3 underwent bronchoscopy due to positive BG results. All proven IFI cases were started on antifungal treatment prior to BG availability.

Conclusion

Approximately 87% of BG use in Thailand was ordered in patients with risk factors for IFIs. This could be due to majority of BG test was recommended by ID specialist. Despite being used in right clinical context, 49% had false-positive BG results. Another barrier of BG use in Thailand was high turn-around time due to small numbers of BG ordered and relative high cost to run the assay. Therefore, the utility of BG for aiding diagnosis or management of fungal infection in our setting is limited.

Disclosures

All authors: No reported disclosures.
286. Hepatitis B Vaccine Compliance: Comparing 2-Dose and 3-Dose Vaccines
Authors: Bruxvoort Katia , Slezak Jeff , Huang Runxin , Sy Lina S , Towner William , Ackerson Bradley , Reynolds Kristi , Qian Lei , Carlson Cheryl M , Solano Zendi , Hyer Randall N , Janssen Robert , Jacobsen Steven J
Published: October 2019

Background

Less than 1 in 3 US adults who initiated the 3-dose (0, 1, 6 months) hepatitis B vaccine series have completed it. HepB-CpG (Heplisav-B; Dynavax) is a new licensed adjuvanted vaccine that requires only 2 doses (0, 1 month). As part of a cluster study performed at Kaiser Permanente Southern California, we compared compliance with second dose and series completion for HepB-CpG vs. comparator vaccine (Engerix-B; GlaxoSmithKline) recipients.

Methods

The cohort included adults not on dialysis who received their first dose of hepatitis B vaccine in family or internal medicine departments from 8/7/2018 to 2/1/2019. Second dose compliance was assessed for the full cohort, but series completion was assessed for a subset vaccinated from August 7, 2018 to September 30, 2018 to allow at least 6 months’ follow-up. Compliance rates were estimated using the Kaplan Meier method. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard regression with robust variance to account for within medical center correlation, adjusting for age, race/ethnicity, census block income and education, prior healthcare utilization, and factors that trigger alerts for hepatitis B vaccination (diabetes and testing for sexually transmitted infections).

Results

There were 6500 HepB-CpG and 7733 comparator vaccine recipients (1,442 and 2,604 prior to September 30, 2018). Rates of second dose compliance at 60 days were 32.9% for HepB-CpG and 29.1% for comparator vaccine, and rates of series completion at 210 days were 56.9% and 20.6%. There was no significant difference in second dose compliance (aHR 1.14, 95% CI: 0.91, 1.47), but HepB-CpG recipients were 5 times more likely to complete the series (aHR 5.17; 95% CI: 3.84, 6.98). Second dose compliance and series completion were significantly less likely among Blacks compared with Whites and significantly more likely among Asians, adults ≥60 years compared with those < 30 years, and adults living in census blocks with a median annual income of $40,000–69,000 compared with < $40,000.

Conclusion

Overall, second dose compliance was similar, but series completion was better for HepB-CpG recipients than comparator vaccine recipients, suggesting that the 2-dose vaccine could lead to improvements in coverage and protection against hepatitis B virus.

Disclosures

All authors: No reported disclosures.
303. A Surrogate Rodent Model for Studying Hepatitis C Virus-specific CD8 T-cell Impairment and Vaccine Prevention
Authors: Hartlage Alex S , Kapoor Amit
Published: October 2019

Background

Virus-specific CD8 T cells are essential for control of acute hepatitis C virus (HCV) infections, yet spontaneously fail in most patients leading to lifelong chronicity and increased risk for severe liver diseases. Efforts to study HCV-specific CD8 T-cell impairment have been hampered by a lack of small animal models. Recently, we established a rat model of chronic HCV-like infection using a hepacivirus homolog identified in Rattus norvegicus. The nature of virus-specific CD8 T-cell immunity in this model has yet to be determined.

Methods

Using two MHC class I tetramers against epitopes located in the E1 and NS5B proteins, we tracked the induction and phenotype of virus-specific CD8 T cells during chronic infection. Responses to infection were similarly analyzed in immune rats that had been vaccinated against the NS3-5B proteins, a strategy that is effective in this experimental setting.

Results

Virus-specific CD8 T cells expanded vigorously in liver shortly after infection but did not develop into functional effectors based upon failure to produce cytokines (IFNγ, TNFα, IL-2, IL-4, IL-10, IL-17A) following peptide stimulation. Notably, subversion of responses was not due to viral escape from T-cell recognition, but rather an intrinsic defect in the antiviral response. Indeed, these populations expressed the inhibitory receptor programed cell death-1 and other markers consistent with an arrested effector-like state precluded from long-term memory formation (CD127-CD27+CD28+CD62L-GranzymeB+). In contrast, adenoviral immunization of naïve rats protected virus-specific T cells from functional impairment after infection and supported memory response development, including against the E1 epitope not encoded by vaccine.

Conclusion

Together, our findings reveal a spontaneous failure of virus-specific CD8 T cells following rat hepacivirus challenge that is highly reminiscent of human HCV infections. Furthermore, these results highlight the utility and significance of this model for understanding mechanisms of HCV persistence and protective immunity necessary for the development of effective vaccines and immune interventions.

Disclosures

All authors: No reported disclosures.
312. Treatment of Hepatitis C After Identification of Infection During Universal Screening Approach in Pregnant Women
Authors: Rose Michelle , Allen Myers John , Ryan Nicholas , Prince Alissa , Talbot Morgan , Espinosa Claudia M
Published: October 2019

Background

Identifying asymptomatic individuals with hepatitis C virus (HCV) infection is challenging. Pregnancy presents a unique opportunity to screen women for HCV and then link those positive to care. Universal screening in pregnant women, however, is not recommended by CDC or ACOG. Further, treatment with direct antiviral agents (DAAs) are not currently approved for pregnant women but are warranted following delivery and breastfeeding. We sought to compare treatment uptake before and after universal screening in pregnant women was implemented as the standard of care in our institution and then determine if universal screening leads to increased treatment after pregnancy.

Methods

A retrospective analysis of risk-based HCV screening in pregnant women was used for the first period (2014–2015) and a prospective design was used following 18 months of universal screening (2016–2017). Prenatal data were collected from all pregnant women that sought care at our institution in the prospective part of the study. We tested for differences in relevant outcomes (e.g., screening rates, rate of those eligible for treatment, and those who actually received treatment) between the two periods. Finally, we performed a cost-effective analysis of universal screening considering treatment rates.

Results

During the universal screening period, more women were screened for HCV and diagnosed with chronic infection. Universal screening was not associated with a significant increase in the odds of women receiving treatment after pregnancy. The increased cost for universal screening was $1060 per patient, resulting in an ICER of $219,391 per additional treatment received or $57,734 per quality-adjusted life-year (QALY) gained, which is below the willingness-to-pay threshold to be cost-effective. Universal screening, however, is cost-effective with an ICER well below the established willingness-to-pay threshold of $100,000 per QALY gained, if all women eligible for treatment receive therapy.

Conclusion

Universal screening may not lead to a significant increase in the odds that pregnant women receive DAAs therapy after pregnancy. Barriers to linkage to care should be addressed in an effort to increase antiviral therapy for these women and universal screening should be implemented within this patient population.

Disclosures

All authors: No reported disclosures.
326. Is Antiretroviral Treatment Averting AIDS and non-AIDS Defining Malignancies in Colombia?
Authors: Martínez Buitrago Ernesto , Arévalo Mora Leonardo , Mantilla Suárez Mónica , Valderrama Sandra , Gonzáles Claudia , Fabio Mueses Marín Héctor , Lenis William , Carlos Alzate Angel Juan , Franco Julieta , Sussmann Otto A , Milena Garcia Garzon Martha , Lucía Ramos Tique Olga , Favio Montero Leonardo , Antonio Pardo Rada Jose , Wilmar Tobón Vásquez Jose , Montero Leonardo F
Published: October 2019

Background

The use of effective antiretroviral therapy (ART) has shown to modify the trend of AIDS-defining malignancies (ADM) toward non-AIDS defining malignancies (NADM); however, Latin America is a region with a known late presentation of HIV/AIDS and late initiation of ART, which could not result in averting the incidence of ADM. The epidemiology of cancers that define or not AIDS in people living with HIV in Colombia is not known.

Methods

The purpose of our study was to identify the trend of ADM and NADM and the effect of ART in a collective cohort of 15 centers of 8 cities in Colombia. After the institutional review board approval, the study was conducted as a retrospective chart review of patients with any diagnosis of cancer presented after the diagnosis of HIV and a year before. Demographic and clinical data related to the HIV infection, ART treatment, and cancer diagnosis were analyzed with Stata 12 software, and associations between different variables were made using univariate and bivariate analyses.

Results

A total of 415 patients with malignancies were included since 1986 (table). Most common cancers were Kaposi sarcoma (n = 227; 54.7%), and non-Hodgkin lymphoma (n = 80, 19,3%). Median CD4+ cell count was very low in this population (median 115.5, P25-75 39.5–243) at the time of HIV diagnosis. Most common NADM were skin cancer (n = 22; 5.3%) and Hodgkin lymphoma (15; 3.6%). The ratio of ADM:NADM was 0.5 before 1995 and increased progressively up to 3.0 after 2010 (P = 0.001) (figure). By bivariate analysis, we found a correlation of ADM with older age (P < 0.001), male gender (P = 0.03), recent years (P < 0.001), lower CD4 and higher VL at the time of cancer (P < 0.0001 for both), and mortality (P = 0.027). Cancer-associated mortality was 3.9%.

Conclusion

The trend for diagnosis of ADM in Colombia is increasing despite antiretroviral treatment and exceeds NADM diagnosis. Potential explaining factors are the late presentation and initiation of ART, and poor treatment success in this population. Special efforts are required to diagnose and treat HIV patients in Colombia to avert this worrying trend.

Disclosures

All authors: No reported disclosures.
329. Health Disparities Among HIV-Positive Patients with Kaposi’s Sarcoma
Authors: Knights Sheena , Lazarte Susana , Kainthla Radhika , Krieger Demi , Bhattatiry Mitu , Chiao Elizabeth , Nijhawan Ank E , Nijhawan Ank E
Published: October 2019

Background

Kaposi’s sarcoma (KS) is an AIDS-related condition that is mediated by HHV-8. Although incidence and mortality of KS in the United States have decreased over time since the advent of HAART, there may be disparities in mortality based on geographic location and race/ethnicity, particularly African-American men in the South.

Methods

A retrospective electronic medical record review was conducted using integrated inpatient and outpatient data in EPIC from PHHS. We included all individuals with a diagnosis of HIV and Kaposi’s sarcoma between January 1, 2009 and December 31, 2018 based on ICD-9/10 codes. We collected demographic information, HIV history, variables related to HIV and KS diagnosis, treatment and outcomes data for each patient. We calculated hazard ratios using Cox proportional hazards modeling.

Results

We identified 252 patients with KS. 95% of patients were male, and the majority were MSM (men who have sex with men; 77% of all patients). 35% of patients were Hispanic, 34% were African-American and 31% were Caucasian. Over half (56%) of patients were funded through Ryan White or were uninsured. The median CD4 count and viral load at the time of cancer diagnosis were 44 and 73,450, respectively. 24% of patients were confirmed to have died by the end of the study time frame. However, due to loss to follow-up, 35% of the cohort had an unknown vital status at the time of the final chart review. Variables most strongly associated with mortality were >2 hospitalizations in the first 6 months of cancer diagnosis (aHR=4.93, P = 0.0003), IV drug use (aHR=3.61, P = 0.0009), and T1 stage of KS (aHR= 2.13, P = 0.0264). African American patients had lower survival than Caucasian or Hispanic patients, with a 5-year survival of 69%, 81% and 80% respectively, although this did not reach statistical significance (aHR 1.77, P = 0.1396).

Conclusion

We describe a large cohort of patients with HIV and HHV-8-related disease, who are predominantly of minority race/ethnicity, uninsured, and have advanced HIV disease. Factors associated with mortality include Black/African-American ethnicity, number of hospitalizations, IV drug use and T1 stage of KS. Our mortality analysis is limited due to high lost to follow-up rates, so we suspect overall mortality in our cohort is higher than currently reported.

Disclosures

Ank E. Nijhawan, MD, MPH, Gilead Sciences, Inc.: Research Grant.
341. Risk of Type 2 Diabetes Mellitus after Antiretroviral Therapy Initiation in Individuals Living with HIV in the United States
Authors: Hsu Ricky , Brunet Laurence , Fusco Jennifer S , Mounzer Karam , Vannappagari Vani , Henegar Cassidy , van Wyk Jean A , Curtis Lloyd D , Lo Janet , Fusco Gregory
Published: October 2019

Background

Limited data exist on the risk of type 2 diabetes mellitus (T2DM) with the use of integrase inhibitors. We assessed the risk of incident T2DM with antiretroviral therapy (ART).

Methods

ART-naïve (ART-N) and -experienced, suppressed (ART-ES; baseline viral load 13 years of age initiating dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL) or boosted darunavir (bDRV) in the OPERA® cohort. After excluding prevalent prediabetes/T2DM and missing baseline covariates, incidence rates of T2DM (i.e., diagnosis, antidiabetic drug, and/orHbA1C >6.5%) were estimated with Poisson regression. The association between core agents and incident T2DM was estimated with multivariate Cox proportional hazards regression adjusted for age, sex, race, HCV co-infection and BMI at baseline. Median (IQR) absolute BMI change from baseline was evaluated at 6, 12, 18, and 24 months in those who developed incident T2DM and those who did not. All analyses were stratified by ART experience.

Results

Individuals prescribed these ART regimens varied significantly (Figure 1). Overall, incidence rate per 1,000 person-years was low for T2DM (ART-N IR: 9.1; 95% CI: 7.5, 10.9; ART-ES IR: 13.3; 95% CI: 11.6, 15.2; Figure 2). Among ART-N initiators, no statistical difference was observed in the risk of progression to T2DM between DTG and EVG/c (aHR: 0.70; 95% CI: 0.47, 1.05) or bDRV (aHR: 0.53; 95% CI: 0.26, 1.04); RAL could not be evaluated due to the small number of T2DM events. Among ART-ES initiators; no difference was observed between DTG and EVG/c (aHR: 0.96; 95% CI: 0.70, 1.33), RAL (aHR: 1.17; 95% CI: 0.70, 1.96) or bDRV (aHR: 0.90; 95% CI: 0.57, 1.42) (Figure 3). A greater absolute change in BMI was observed for ART-N initiators developing T2DM at all timepoints; reaching statistical significance at 12 and 18 months (Figure 4). No differences were observed for ART-ES initiators.

Conclusion

Incident T2DM was uncommon among ART-N and ART-ES persons initiating DTG, EVG/c, RAL or bDRV in this large clinical population. None of the comparisons between DTG and other core agents showed a statistically significant increased risk of T2DM. However, due to the small number of events in the ART-N population differential risk cannot be excluded and monitoring HbA1c remains prudent.

Disclosures

All authors: No reported disclosures.
354. Efficacy of Second-Generation Direct Acting Antivirals in the Setting of HCV/HIV Co-infection and Cirrhosis: A Review of Real-World Treatment Experiences
Authors: Saba Nicholas , Chirch Lisa , Banks Sarah H , Wu Geroge , Einstein Michael
Published: October 2019

Background

Patients co-infected with HIV and HCV represent a unique subpopulation with specific high-risk characteristics including increased transmission efficiency of HCV, higher HCV viral load and more rapid progression of liver disease when compared with mono-infected patients. Although virologic failure is rare in the direct acting antiviral (DAA) era, we have anecdotally observed a high rate of failure in our patients who are co-infected and have cirrhosis. Our objective was to evaluate the impact of cirrhosis on co-infected patients compared with co-infection without cirrhosis and mono-infected patients with cirrhosis as it relates to cure of HCV treated with DAAs.

Methods

A retrospective chart review was performed. Patients from UConn Health Infectious Diseases and Gastroenterology clinics and Hartford Hospital Comprehensive Liver Center treated January 1, 2014 through December 31, 2017 were included. Patients were grouped as follows: (1) HCV/HIV coinfected without cirrhosis, (2) HCV/HIV coinfected with cirrhosis, (3) HCV infected with cirrhosis. Data were analyzed in SAS, variables were compared by chi square analysis and Fishers Exact test to determine statistical significance.

Results

No differences in baseline characteristics were noted (Table 1). Cirrhotic patients were 63% of the total cohort. There was no statistical difference in the rates of sustained virologic response (SVR) among the 3 groups. The overall rate of SVR was 95%. SVR for patients with cirrhosis (co- and mono-infected) was 92%. All treatment failures (n = 3) in this cohort had cirrhosis. Among the 38 cirrhotic patients, 3 (8%) had treatment experience with DAAs. In contrast, none of the non-cirrhotic patients had prior DAAs. The use of protease inhibitors or ribavirin had no impact on cure; ribavirin was evenly distributed between the two groups with cirrhosis. SVR rates were lower with genotypes 2–4 as compared with genotype 1. No immunologic or virologic factors were correlated with SVR.

Conclusion

We found no differences in rates of SVR in coinfected patients with or without cirrhosis. However, all treatment failures were noted in patients with cirrhosis, and cirrhotic patients tended to have treatment experience with DAAs. Whether coinfected patients with cirrhosis should be managed differently will require additional study.

Disclosures

All authors: No reported disclosures.
368. Incidental Findings on Brain MRI in People Living with HIV
Authors: Hanna Kevin F , Sayles Harlan R , O’Neil Jennifer , White Matthew , Wilson Tony , Swindells Susan
Published: October 2019

Background

HIV infection is associated with an array of neurocognitive changes, collectively referred to as HIV-Associated Neurocognitive Disorder (HAND). These changes have been the subject of a great deal of study, often including structural MRI of the brain. Incidental findings (IF) are a well-known complication of imaging studies done for both diagnostic and research indications, and can pose important ethical and clinical dilemmas. Little is known about the rates and types of IF found on brain MRI in patients with HIV infection. We identified and characterized such findings in participants who participated in a study of neurophysiological markers of HAND.

Methods

The parent study included 108 HIV-infected adults and 125 demographically matched uninfected controls without cognitive impairment who had undergone T1-weighted structural brain MRI for research purposes. Demographic and diagnostic data were abstracted from the research records. Each MRI study was read by the same neuroradiologist, blind to the participant’s HIV status. IF were classified as vascular, neoplastic, congenital, other neurologic, or non-neurologic. Categorical measures were compared using Pearson chi-square tests while continuous measures were compared using t-tests.

Results

Among HIV-infected participants, 36/108 (33.3%) had IF compared with 33/125 (26.4%) of controls (P = 0.248). Rates of IF were significantly correlated with increased age in both HIV-infected and control participants. We found no correlation among presence or absence of IF and sex, race/ethnicity, or CD4 count and HAND status for the HIV-infected cohort. The most common categories were neurologic (27), followed by non-neurologic (8), vascular (6), and neoplastic (2) (Table 1).

Conclusion

If were common in both HIV-infected participants and controls, at higher rates than previously reported, possibly because of increased sensitivity of MRI machines over time. Surprisingly, we found no significant difference between the groups and no correlation with HAND status or CD4 count. Age was the only factor correlated with rates of IF in either HIV-infected participants or controls. To our knowledge, this study is the first of its kind to characterize incidental findings in HIV-infected patients.

Disclosures

All authors: No reported disclosures.
370. Comparing Trends and Outcomes among HIV-Infected vs. HIV Uninfected Patients with Tuberculosis: A 5-Year Experience Within the Florida Department of Health in Hillsborough County
Authors: Moore-Pardo Shylah M , Addisu Anteneh , Reljic Tea , Aslam Sadaf , Casanas Beata
Published: October 2019

Background

Although the rate of tuberculosis (TB) has significantly declined in the United States, elimination has plateaued. Florida is one of the states with the greatest number of cases. The majority of cases occur in foreign-born individuals. Human immunodeficiency virus (HIV) is also a major contributor. HIV-TB coinfection leads to reciprocal interactions with significant clinical impact. We aim to compare the risk factors, clinical findings, and outcomes among HIV-infected vs. HIV uninfected patients.

Methods

A retrospective cohort study of TB cases over a 5 year period (2012–2017) was conducted. All patients with HIV co-infection with age- and gender-matched HIV negative controls were included. The diagnosis of TB was made via clinical, microbiological, radiological, and/or PCR based methods. SPSS was used for statistical data analysis.

Results

A total of 411 TB cases were identified and 66 patients (33 HIV-infected plus 33 HIV un-infected) were eligible for inclusion. The median age was 49 years (range 22–70). The male to female ratio was 21:12 and 50% of patients had TB symptoms; the rest had abnormal imaging or lab finding. Cases were confirmed via positive sputum smear, culture, or PCR (Figures 1–3). Only 11 patients were lost to follow-up, thus 83.3% completed therapy. A total of 5 persons died (Table 1).

Conclusion

The rate of HIV-TB coinfection in the United States was 5.3% in 2018; higher among injection drugs users, homeless persons, inmates, and alcoholics. In our study, the rate of HIV-TB coinfection was slightly higher (8%). The difference was not statistically significant in regards to foreign born, homelessness, and incarceration. Only 3 patients admitted to injection drug use and 9 used alcohol (all HIV negative). Traditionally, HIV-TB coinfected patients have extra-pulmonary TB with higher rates of negative sputum and are at increased risk of death. In our cohort, the difference was statistically significant (P = 0.009) only for cavitary TB (predominated in HIV un-infected) but no difference in outcomes was observed between the two groups. These findings suggest changing trends in HIV-TB coinfection which may be partly related to our setting and demographics but may be attributed to better access to care and antiretroviral therapy at large.

Disclosures

All authors: No reported disclosures.
375. Cryptococcal Antigenemia in Advanced HIV Infection
Authors: Ahuja Jatin , Soneja Manish , Wig Naveet , Xess Immaculata , Biswas Ashutosh , Singh Gagandeep , Vibha Deepti , Nischal Neeraj
Published: October 2019

Background

Diagnostic importance of asymptomatic cryptococcal antigenemia is being increasingly recognized in the last few years. Recently, WHO (World Health Organization) has recommended routine screening of CrAg (cryptococcal antigen) among PLHA with CD4 ≤100/mm3, albeit this procedure is not yet adopted by many developing countries including India.

Methods

We conducted a prospective observational study in a large tertiary care center of North India, upon ethical clearance. Latex agglutination test was performed to assess serum CrAg levels, followed by the lumbar puncture for detection of CrAg levels in the CSF. We analyzed the prevalence and treatment outcomes of cryptococcal antigenemia among PLHA with CD4 ≤ 100 cells/mm3. Detailed clinical examination was conducted, with follow-up of upto 3 months. Multivariate analysis was performed for the estimation of risk factors.

Results

The mean age (years) and BMI (kg/m2) of all the participants were 41.4 ± 11.2 and 22.1 ± 2.6, respectively. Notably, the mean CD4 count (cu.mm) at the time of recruitment was 62.3 ± 20.5. Noteworthy, 62 (60.8%) of the patients were ART naïve. We found 9.8% (n = 10) of the patients were positive for serum CrAg, and only 2.9% (n = 3) had clinical features of meningitis and 6.8% (n = 7) were asymptomatic (subclinical) CrAg positive. Strikingly, 3.9% (n = 4) of the asymptomatic cryptococcal antigenemia patients were also positive for CrAg in CSF, with 1.9% (n = 2) were only serum CrAg positive, and 1 patient was lost to follow-up (Graph 1). Multivariate analysis revealed that patients with long duration of HIV (P = 0.04), headache symptoms (P = 0.004) and possessing features of meningismus (P value=0.08) are more likely to be CrAg positive. Conversely, patients on fluconazole were protective against cryptococcal antigenemia (P = 0.1) as shown in Table 1. Overall mortality observed was 11.3% among advanced HIV patients. Moreover, mortality in CrAg-positive patients was 33.3% in comparison to CrAg-negative patients who had 9% (P = 0.06) in 3-months follow-up.

Conclusion

Cryptococcal antigenemia is common (9.8%) among patients with CD4 count ≤100/mm3 in India. Screening for CrAg should be made routine for PLHA with CD4 count ≤100/mm3 and if required preemptive treatment to be given in this regard.

Disclosures

All authors: No reported disclosures.
382. Difference in Pathogens Between Hip and Knee Prosthetic Joint Infection
Authors: Henry Michael , Kapadia Milan , Nguyen; Barry Brause Joseph , Miller Andy O
Published: October 2019

Background

There is contradicting evidence characterizing the difference in pathogens that cause hip and knee prosthetic joint infection (PJI). A possible difference in microbiology may inform choice in antibiotic etiology, prophylaxis, and empiric treatment. We sought to analyze a large cohort of PJIs to see whether there was a significant difference in pathogen between joints.

Methods

A retrospective cohort of hip and knee PJIs, from 2008 to 2016, were identified by ICD code and surgical codes. The PJI pathogen was identified from synovial or intra-articular tissue cultures. The Student’s t-test was used to compare continuous variables. Chi-square tests were used to compare the categorical variables to joint.

Results

807 PJI cases were identified including 444 knees and 363 hips. There were no significant differences between hip and knee PJIs in age, sex, history of PJI, rheumatoid arthritis, Charlson comorbidity index and laterality. There was a higher frequency of diabetes in knee PJIs (25.3%) compared with hip PJIs (15.7%), P < 0.001. No significant difference was found in the prevalence of fungal, staphylococcal (including Staphylococcus aureus), streptococcal, or enterococcal pathogens between hip and knee PJIs.

Conclusion

In this single-center cohort, hip and knees PJIs are infected with similar pathogens. Multiple site studies are needed to characterize the microbiology of PJIs at a larger scale.

Disclosures

All authors: No reported disclosures.