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The article presents a study which examined the incidence and risk factors of herpes zoster (HZ) in the general U.S. population using data from the U.S. Military HIV Natural History Study (NHS). Topics discussed include comparison of participants with and without HZ, independent predictors of HZ, and factors associated with HZ in NHS participants who contributed follow-up time after 2001.

Aim To evaluate prior prevalence of HIV indicator conditions in late-presenters with HIV infection. Design Retrospective cohort study between 2000 and 2014 in a healthcare network in Melbourne, Australia comparing patients presenting with late diagnosis of HIV infection (CD4 < 350 cells/ml) to those patients who had a CD greater than or equal to 350 cells/ml at presentation. Method The European AIDS Clinical Society guidelines on HIV indicator guided testing were used to assess for any indicator conditions in their prior medical history which may have represented a missed opportunity for earlier diagnosis. Main outcome measures: Descriptive statistics and prevalence of HIV indicator conditions. Results Of 436 patients with HIV infection, 82 were late presenters. Late presenters were more commonly male (83% vs. 75%, P = 0.11), older (mean age 45 vs. 39 years), born overseas (61% vs. 58%, P = 0.68) and report heterosexual transmission as their exposure risk (51% vs. 31%, P < 0.001). Of 80 patients with late presentation of HIV infection, 54 (55%) had at least one, 29 (36%) at least 2, 12 (15%) at least 3 and 5 (6%) had 4 or more previous HIV indicator conditions which would have triggered HIV testing according to guidelines. The most common indicator conditions were: unexplained loss of weight (31%), herpes zoster (10%), thrombocytopenia or leukopenia (10%), oral or oesophageal candidiasis (10%) and community acquired pneumonia (9%). Twenty patients (25%) had HIV indicator conditions diagnosed at least 12 months before the eventual diagnosis of HIV infection. Discussion/ Conclusion Patients diagnosed with late-presenting HIV often had an HIV indicator condition prior to presentation, presenting a missed opportunity for earlier diagnosis. [ABSTRACT FROM AUTHOR]

Background Adults with immunocompromising conditions are at increased risk of herpes zoster (HZ) infection and related complications. We aimed to assess the incidence of HZ seen in hospital or emergency department in immunocompromised populations and compare it to that of immunocompetent populations. Methods Using healthcare administrative data, we calculated incidence rates (IR) of HZ in Ontario, Canada between April 1, 2002 and August 31, 2016 in adults ≥18 years categorized as immunocompromised or immunocompetent. We repeated these analyses by type of immunocompromising condition and provided incidence rate ratios (IRR) comparing to immunocompetent adults. We also calculated IRs and IRRs of HZ complications by immunocompromised status. Results There were 120,654 incident cases of HZ seen in hospital or emergency department during the study period. Immunocompromised adults accounted for 13% of these cases despite representing only 3% of the population. The risk of HZ was higher for immunocompromised adults compared with immunocompetent (IRR = 2.8, 95% CI 2.8–2.9) and ranged across type of immunocompromising condition (from 2.4 [95% CI 2.3–2.5] in those with a solid tumor malignancy to 11.0 [95% CI 10.0–12.0] in those who had undergone a hematopoietic stem cell transplant). The risk of any HZ complication was also higher in immunocompromised adults (IRR = 3.5, 95% CI 3.4–3.6) and was highest for disseminated zoster (IRR = 31.5, 95% CI 26.3–37.5). Conclusion The risk of HZ and related complications was higher in immunocompromised populations compared with immunocompetent. Our findings underscore the high-risk nature of this population and the potential benefits that may be realized through HZ vaccination of this group. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background The two known primary risk factors for herpes zoster (HZ) are age and immunodeficiency yet estimates of HZ risk by immunocompromising medical condition have not been well characterized. We undertook a systematic review of the literature to estimate HZ risk in six categories of immunocompromised patients. Methods We conducted a systematic review of evidence for HZ in patients with hematopoietic cell transplants (HCT), cancer (blood and solid tumor), HIV, and solid-organ transplant (SOT; kidney and other). We identified studies in Pubmed, Embase, Cochrane, Scopus and clinicaltrials.gov using the following outcome search terms: Herpes Zoster, Shingles, VZV, chickenpox, Varicella-zoster virus, or opportunistic infection. We included articles that presented original data from studies in the United States on risk of HZ in adults and were published after 1992 (1996 for HIV). Case reports and conference abstracts were excluded. We assessed risk of bias with Cochrane (clinical trials) or GRADE (observational) methods and categorized studies as high, medium, or low risk. Results We identified and screened 3,765 records; 57 articles were abstracted and 34 deemed low or moderate risk of bias (Figure 1). All articles reported at least one estimate of HZ cumulative incidence, which ranged from 0% to 41%. Thirteen studies estimated HZ incidence, which varied widely within and between immunocompromised populations (Figure 2). The highest estimates were seen in HCT (median = 52 HZ cases/1000 patient-years), followed by blood cancers and SOT, and then solid tumor cancers and HIV (median = 13 HZ cases/1,000 patient-years). Among 17 studies of HCT patients, longer follow-up time and absent or <1 year of post-transplant antiviral prophylaxis were associated with higher HZ cumulative incidence (Figure 3). Conclusion HZ is common among all immunocompromised populations studied—exceeding expected HZ incidence in immunocompetent middle-age adults. Antiviral prophylaxis among HCT patients has an ameliorating effect but long-term HZ risk following discontinuation is unclear. Better evidence for incidence and severity of HZ in immunocompromised populations is needed to inform economic and HZ vaccine policy analyses. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Ruxolitinib is an inhibitor of Janus kinase (JAK) 1 and 2 and is approved for the treatment of myelofibrosis and polycythemia vera. Infectious complications associated with its use include reactivation of herpes simplex, zoster, hepatitis B, and tuberculosis, mucormycosis, and progressive multifocal leukoencephalopathy. Methods Seven cases of ruxolitinib-associated cryptococcal infections have been reported: three cases of meningitis, two cases of pulmonary disease, and two cases of disseminated disease (Table 1). Results We present a 72-year-old male with a history of JAK-2-positive polycythemia vera with secondary myelofibrosis, and concurrent multiple myeloma who presented with 3 weeks of chronic cough and 3 days of fever with severe bifrontal headache after remodeling a large birdcage in his backyard. The patient was on ruxolitinib, ixazomib, and weekly dexamethasone. Cerebrospinal fluid (CSF) analysis showed an elevated opening pressure of 29 cm of CSF, 173 leucocytes with a predominance of lymphocytes, protein of 87 mg/dL and a normal glucose level. BioFire FilmArray® Meningitis/Encephalitis panel detected targets for Cryptococcus in the CSF, and CSF cryptococcal antigen was positive at 1:4. CSF fungal cultures were subsequently positive for Cryptococcus neoformans, susceptible to liposomal amphotericin B (LAMB) and fluconazole. Ruxolitinib was discontinued, treatment with LAMB and flucytosine (5-FC) was associated with significant improvement of headache over the next week. Repeat CSF analysis in 2 weeks was culture negative with a negative cryptococcal antigen test. The patient completed 3 weeks of LAMB and 5-FC and then transitioned to oral fluconazole for a year. Conclusion Ruloxitinib and other JAK inhibitors suppress host immunity through impaired T-cell activation and downregulation of cytokines. The JAK-Signal Transducer and Activator of Transcription pathway is one of the most active pathways in host defense against cryptococcus, and use of JAK inhibitors like ruxolitinib may predispose to severe cryptococcal infections. Bird exposure is a risk factor, making environmental contact counseling for patients on ruxolitinib important. Fluconazole prophylaxis needs to be considered in select cases. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background In the pivotal clinical trials, ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229), the adjuvanted recombinant zoster vaccine (RZV) showed high efficacy against herpes zoster and postherpetic neuralgia. The incidence of reported solicited events was higher in RZV compared with placebo recipients. Methods In these phase III, observer-blind, placebo-controlled trials conducted in 18 countries, adults ≥50 years of age (YOA, ZOE-50) and ≥70 YOA (ZOE-70), randomized 1:1, received 2 doses of RZV or placebo 2 months apart. Injection-site and general events were solicited for 7 days after each dose via diary cards in a participant subset. For this post-hoc analysis, ZOE-50 and ZOE-70 data from participants having completed the diary cards for both RZV doses were pooled. The intensity of each solicited event after dose 2 was stratified by the intensity of the same event after dose 1. Results Solicited injection-site and general events were recorded for both RZV doses by 4,676 and 4,668 vaccinees, respectively (Figure 1). Of 1,235 vaccinees with no injection-site event at dose 1, 881 (71.3%) reported no injection-site event and 20 (1.6%) reported a grade 3 event after dose 2. A total of 433 (9.3%) vaccinees reported a grade 3 injection-site event, either after dose 1 or dose 2. Of 244 vaccinees with grade 3 injection-site events at dose 1, 79 (32.4%) also reported a grade 3 event after dose 2. Of 2,312 vaccinees with no general event at dose 1, 1,617 (69.9%) reported no general event and 67 (2.9%) reported a grade 3 event after dose 2. A total of 499 (10.7%) vaccinees reported a grade 3 general event, either after dose 1 or dose 2. Of 222 vaccinees with grade 3 general events at dose 1, 81 (36.5%) also reported a grade 3 general event after dose 2. In general, vaccinees who did not experience a certain event after dose 1, did not experience this event after dose 2 either. Most vaccinees reporting a specific event at high intensity after dose 1, reported the same event at a lower intensity (or not at all) after dose 2 (Figures 2 and 3). Conclusion While not powered to predict event intensity of the second RZV dose, our data provides an overview of event intensity after RZV dose 2 according to the intensity of the same event experienced after dose 1. Funding: GlaxoSmithKline Biologicals SA. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background The adjuvanted recombinant zoster vaccine (RZV) is efficacious in preventing herpes zoster in adults ≥ 50 years. The current study investigates whether the vaccinees' quality of life (QoL) and physical functioning (PF) are impacted by local and systemic reactions due to RZV. In a previous report of this phase III, open-label, multicenter study (NCT02979639), overall PF and QoL were not significantly affected by a first RZV dose. [1] Here we report the results from the same study after a second RZV dose and safety results from dose 1 up to study end. Methods Adults aged ≥ 50 years were to receive 2 doses of RZV 2 months apart. Changes in mean Short Form health survey (SF-36) PF score between pre- and post-each RZV dose for 7 days, QoL, reactogenicity and safety were assessed. Results 401 adults received dose 1 and 391 received dose 2 of RZV. Post-second RZV dose, the reported solicited local symptoms were pain (75.1%), erythema (22.4%) and swelling (13.9%), and the most frequent solicited systemic symptoms were fatigue (46.3%), headache (37.5%) and myalgia (32.9%). Grade 3 solicited symptoms were reported by 7.2% (local) and 11.1% (general) of participants, and 5 (1.2%) participants reported reactogenicity triggering medical attention post-second RZV dose. From first dose up to study end, 14 (3.5%) participants reported 21 serious adverse events, none related to RZV. In days 1–2, post-second RZV dose, a transient, clinically-important decrease in SF-36 PF score (table) was seen in those reporting grade 3 solicited symptoms, which impacted activities such as walking and climbing stairs. Overall, during the 7 days post-second RZV dose, a mean change of −0.4 points was observed from the mean baseline score, indicating the PF was not clinically meaningfully impacted. No overall quality-adjusted-life-year loss was recorded. Conclusion Overall, the QoL and PF of adults ≥ 50 years were not affected post-second RZV dose; a transient impact was observed in adults with grade 3 reactogenicity. These results and the observed reactogenicity and safety profile are consistent with first RZV dose results, as well as that of previous studies with the RZV vaccine in adults of similar age. Funding: GlaxoSmithKline Biologicals SA. 1. Schmader et al. Abstract 2488, IDWeek 2018 Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background The adjuvanted recombinant zoster vaccine (RZV, GSK), indicated for the prevention of herpes zoster (HZ) in adults ≥ 50 years of age, received its first marketing authorization in October 2017. We reviewed the post-marketing spontaneous adverse event (AE) reports submitted to GSK's worldwide safety database since RZV introduction. Methods Descriptive analyses were conducted on all spontaneous reports involving RZV from October 13, 2017 to February 10, 2019. Observed-to-expected analyses were performed for the outcomes of interest: all-cause mortality and the 2 most commonly reported potential immune-mediated diseases, Guillain–Barré syndrome (GBS) and Bell's palsy. Data mining was done to detect quantitative signals by identifying RZV-AE pairings with disproportionate reporting or evidence of an unexpected time-to-onset distribution. Results Most of the15,638 spontaneous reports received were medically verified (75.2%), originated from the United States (81.7%) and were non-serious (95.3%). Reports were mainly from individuals 50–69 years old (62.1%) and females (66.7%), when documented (Figure 1). Of all reports, 12,059 (77.1%) described signs/symptoms and 3,579 (22.9%) described vaccination errors, majority of which were without associated signs/symptoms (2,961; 82.7%). Overall, the most commonly reported signs/symptoms were consistent with vaccine reactogenicity (such as injection-site reactions, pyrexia, pain, chills, headache, fatigue), which were previously reported after RZV (Table 1). The observed reporting rates of outcomes of interest likely represent temporary associated events that are occurring as background incidence in the general population. No unexpected reporting patterns were detected overall. The proportion of RZV vaccination errors over time, by country, is shown in Figure 2. Overall, most reports described errors in vaccine preparation and reconstitution (29.7%) (Table 2). Conclusion Overall, the safety profile of RZV, following the first year of post-marketing use, is reassuring and consistent with that observed in clinical trials. Ongoing surveillance will continue to monitor RZV safety, as it is an early stage in the implementation, when real-life data are limited. Funding: GlaxoSmithKline Biologicals SA. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background In October 2017, the Centers for Disease Control and Prevention (CDC) recommended the adjuvanted Recombinant Zoster Vaccine (RZV) for all adults aged ≥ 50 years, regardless of previous vaccination. Understanding patient preferences for herpes zoster (HZ) vaccination can inform providers, payers, and policymakers about barriers, hesitancies, and utilization of available vaccines. Methods A discrete choice experiment survey was completed by 1,454 US adults aged ≥50 years in January 2019, with targeted sampling quotas of African Americans (25%), recent influenza vaccine recipients (50%), and individuals with autoimmune disease or chronic comorbidities (37%), to enable subgroup analyses. HZ vaccine profiles were characterized using seven attributes: vaccine efficacy (VE), duration of protection, location of service, number of doses, injection-site reaction severity, systemic reactions duration, and out-of-pocket (OOP) costs. In a series of choice questions, respondents chose between a pair of hypothetical HZ vaccine profiles, determined by an efficient experimental design, and a no vaccination option. In a second series, respondents stated intentions to complete a 2-dose vaccination series, conditioned on varying levels of side effects experienced with a first dose and expected OOP costs. Differences across subgroups were explored. Results Respondents placed the greatest weight on OOP costs and VE when choosing among HZ vaccination options (Figure 1). African American respondents were more sensitive to increases in OOP costs than non-African American respondents (Figure 2). ~75% of respondents indicated they would complete the series of a two-dose HZ vaccine if the cost of completing the series was $8-$13. Second-dose compliance drops about 25% when OOP costs increase to $140–150. Conclusion OOP cost had the greatest influence on respondents' intention to select and complete HZ vaccination. Efforts to remove financial barriers to improve implementation of the CDC recommendations for HZ vaccination should be considered. GlaxoSmithKline Biologicals SA, GSK study identifiers: 208677/HO-17-18066. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background The burden of herpes zoster (HZ) is significant worldwide, with millions affected and the incidence rising. Current literature has identified some risk factors for this disease; however, there is yet to be a comprehensive study that pools all evidence to provide estimates of risk. Therefore, The purpose of this study was to identify various risk factors, excluding immunosuppressive medication, that may predispose an individual to developing herpes zoster. Methods The literature search was conducted in MEDLINE, EMBASE, Cochrane Central, Cochrane Systematic Reviews, Web of Science, CAB Direct, yielding case–control, cohort and cross-sectional studies that were pooled from January 1966 to September 2018. Search terms included: zoster OR herpe* OR postherpe* OR shingle* AND risk OR immunosupp* OR stress OR trauma OR gender OR ethnicity OR race OR age OR diabetes OR asthma OR chronic obstructive pulmonary disease OR diabetes. Risk ratios for key risk factors were calculated via natural logarithms and pooled using random effects modeling. Results From a total of 4417 identified studies, 93 were included in analysis (n = 3826134 HZ cases). Immunosuppression through HIV/AIDS (RR 3.25; 95% CI 2.47–4.27) or malignancy (RR 2.17; 95% CI 1.86–2.53) significantly increased the risk of HZ compared with controls. Family history was also associated with a greater risk (RR 2.48; 95% CI 1.70–3.60), followed by physical trauma (RR 2.01; 95% CI 1.39–2.91) and older age (RR 1.68; 95% CI 1.41–2.01). A slightly smaller risk was seen those with psychological stress, females, and comorbidities such as diabetes, rheumatoid arthritis, cardiovascular diseases, renal disease, SLE, and IBD compared with controls (RR range: 2.08 to 1.25). We found that black race had lower rates of HZ development RR 0.69 (95% CI 0.56–0.85). Conclusion This study demonstrated patients with family history of HZ, older age, female sex, have particular comorbidities or are immunosuppressed have an elevated risk of herpes zoster. Patients with these characteristics are prime candidates for vaccination. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Of the nine human herpesviruses (HHVs), most viruses have neurovirulence. Clinical manifestations of central nervous system (CNS) complications caused by some of the HHVs are well examined in children and immunocompromised adults; however, information of EBV and β-herpesviruses in an immunocompetent adult is limited. Methods Between April 2013 and March 2018, 322 patients (median age; 51.6 years old, male/female; 196/126) suspected to CNS infection were enrolled in this study. Patients with unconsciousness or characteristic change lasting more than 24 hours and abnormal brain MRI or EEG were defined as encephalitis. Real-time PCRs for detection of the 7 HHVs DNA including HSV-1, HSV-2, VZV, CMV, EBV, HHV-6, and HHV-7 were carried out in DNA extracted from 200 μL CSF. HHV-6 was discriminated between HHV-6A and HHV-6B using RFLP analysis. Results Herpesviruses DNA was detected in 33 (10.2%) of the 322 patients. The most frequently detected HHVs was VZV (19 cases) and followed by HHV-6B (4 cases), HSV-1 (3 cases), HSV-2 (3 cases), and EBV (2 cases). Multiple HHVs DNAs were detected from the 2 patients (case A; HSV-2, HHV-6, and EBV, case B; EBV and HHV-6B). No CMV and HHV-7 DNAs were detected in any of the samples. Eleven cases were assigned as encephalitis, and other 22 cases were non-encephalitis. Although all 3 patients with positive HSV-1 DNA were encephalitis, all 3 patients with positive HSV-2 DNA were meningitis. Fourteen (13 patients had zoster) of the 19 patients with positive VZV DNA were meningitis, and the remaining 5 patients (4 patients had zoster) were encephalitis. Two of the 4 HHV-6B-positive patients were non-encephalitis, one patient was diagnosed Orbital apex syndrome and another patient was myelitis. One of the 2 encephalitis patient was chromosomally integrated (ci) HHV-6. Additionally, case B was also ciHHV-6. Conclusion Approximately 10% of the samples were positive of HHVs DNA. VZV was the most frequently detected viral DNA in this cohort. Thirty-three percent of the patients were encephalitis, remaining patients were non-encephalitis such as meningitis and myelitis. As suggested, ciHHV-6 can cause miss-diagnosis of patients suspected with CNS infection. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Addition of integrase strand transfer-inhibitors (mainly dolutegravir) has strengthened anti-retroviral therapy (ART), to sustain viral suppression in HIV-1 and 2-infected patients. For judicious use in the future, we examine weight gain in ART-naïve, and those exposed to INSTI-based regimens as first, second, and third-line ART. Methods We undertook a retrospective cross-sectional study of patients initiated on INSTI-based regimens from 15 January 2017 to 22 December 2018 (n = 333). Descriptive statistical analyses were performed using STATA 15.1. Cross-tabulation and stratification were conducted to measure the strength of association. A linear regression model was used to study the increase in weight per unit of time. Results 331 patients are infected with HIV-1 and 2 with HIV-2. 66% are male, median age= 38 years (IQR 31–44). Median CD4 count at INSTI initiation was 226 cell/cubic mL (IQR 87–395). Median viral load at initiation of INSTI-based therapy was log104.768 copies/mL (IQR 2.9—5.63). Most common opportunistic infections were pulmonary tuberculosis (n = 97), oral candidiasis (n = 84), and herpes zoster (n = 44). Median hemeoglobin was 12gm% (IQR 10.5–13.8). 39% were initiated on TDF+3TC+DTG and 32% were initiated on TDF+FTC+DTG. 74% experienced weight gain; average increase was 3.69 Kg (SD 3.56) at 3 months. 19.5% gained >4 kg; median BMI at initiation of therapy was 22.56 kg/m2 (IQR 19.8–25.1) and 25.4 kg/m2 (IQR 22.5–28.7) at an average of 9.5 months post initiation of dolutegravir-based ART. 70% of ART naïve (n = 73) experienced weight gain; 17.8% gained 8.36 kg at 9 months. Higher weight gain was observed in patients with opportunistic infections. Association with gender (OR = 0.9 95%, CI 0.54 -1.5; P = 0.70) and age (OR=0.9, 95% CI 0.97–1.01; P = 0.71) was not significant. Weight gain was positively correlated with time (r=+1); predicted increase in weight per 0.1 months after initiation of INSTI-based regimen (F=4.62, P = 0.032). Conclusion Access and adherence to INSTI have positively influenced viral suppression of HIV-infection.To ensure the prevention of obesity and apt use of ART for malnourished patients, it is imperative to monitor weight gain in patients who are initiated on INSTI-based regimens. Further research to study the mechanism of weight gain is warranted. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background The risk of herpes zoster (HZ) has been reported to vary by sex and ethnicity. In 2 large-scale clinical trials, ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229), the adjuvanted recombinant zoster vaccine (RZV) demonstrated high vaccine efficacy (VE) against HZ and post-herpetic neuralgia (PHN). We present a post-hoc analysis of RZV efficacy against HZ and PHN in the ZOE-50/70 population stratified by sex, geographic region and geographic ancestry/ethnicity. Methods The ZOE-50 and ZOE-70 studies were phase III, observer-blind, placebo-controlled trials conducted across 5 geographic regions. Adults ≥ 50 years of age (YOA; ZOE-50) and ≥ 70 YOA (ZOE-70), randomized 1:1, received 2 doses of RZV or placebo 2 months apart. Here, VE against HZ by sub-population was estimated from the ZOE-50 population (≥ 50 YOA) and the pooled ZOE-50/70 population (pooled ≥ 70 YOA), and VE against PHN by sub-population was evaluated in the pooled ≥ 70 YOA. Results VE was evaluated in 7,340 RZV and 7,413 placebo recipients ≥ 50 YOA (mean age: 62.3 [RZV], 62.2 [placebo] YOA) and 8,250 RZV and 8,346 placebo recipients in pooled ≥ 70 YOA (mean age: 75.5 [RZV, placebo] YOA). VE against HZ and PHN was similar for women and men in the ≥ 50 YOA and pooled ≥ 70 YOA (Tables 1 and 2). Point estimates for VE against HZ by geographic region ranged from 95.7% to 97.2% in ≥ 50 YOA and from 87.3% to 95.1% in pooled ≥ 70 YOA (Table 1). Point estimates for VE against PHN by geographic region ranged from 86.8% to 100% in pooled ≥ 70 YOA. VE was similar across geographic ancestry groups in pooled ≥ 70 YOA: VE point estimates against HZ ranged from 89.6% to 100% and VE against PHN ranged from 87.5% to 100% (Tables 1 and 2). VE against HZ was 88.1% and against PHN was 65.9% in Hispanic participants in pooled ≥ 70 YOA (Tables 1 and 2). Conclusion Acknowledging the limitations including the post-hoc character of these analyses and the small number of participants and cases available, our data suggest that RZV is efficacious against HZ and PHN irrespective of sex, geographic region, geographic ancestry, and ethnicity. Funding: GlaxoSmithKline Biologicals SA. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Social media is frequently used to share medical information. Current European regulatory guidance for the pharmaceutical industry calls for reporting valid adverse events (AE) derived from social media as well as consideration of non-valid AEs. This guidance is followed when our company utilizes social media related to any company products and interests. Here we evaluate its application to vaccines. Methods Posts collected from all screened social media sources (company owned, or company reviewed) were examined (August 1, 2017–February 28, 2019) to identify safety-related information pertaining to any of its 14 licensed vaccines. Posts were classified as valid cases (i.e. containing information about company product, AE, and identifiable reporter), non-valid cases (i.e. company product, AE, but missing an identifiable reporter), or not relevant (no safety-related information; not further analyzed). Valid cases were added to the company's safety database; non-valid cases were reviewed for trends requiring further analysis. Both, valid and non-valid cases, were analyzed as part of routine safety surveillance Results Among 69,682 vaccine-related posts reviewed, 285 (0.4%) were valid; 11,464 (16.5%) were non-valid; 47,966 (83.1%) were not relevant. Most non-valid cases concerned the company's 4-valent (8,934 [78%]) or 9-valent (1,420 [12%]) human papillomavirus vaccines, followed by its measles-mumps-rubella (336 [2.9%]), pneumococcal (282 [2.5%]), and herpes zoster (246 [2.1%]) vaccines. Review of data from selected temporal spikes in posts demonstrated that they were usually attributable to increased reposts of an original post or to personal views, rather than containing incremental factual new safety data. Conclusion Fewer than 1% of posts from relevant social media sources contained sufficient information to be considered valid cases. No new safety signals were identified for any of the vaccines from social media cases (valid or non-valid). Among posts containing safety information, the nature of this information tends to be redundant or sentimental, precluding meaningful safety analyses. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background More recent baseline epidemiological data for Herpes Zoster (HZ) in adults ≥ 50 years of age, obtained before the introduction of the adjuvanted Recombinant Zoster Vaccine (RZV), are needed for future evaluations of the impact of RZV on HZ epidemiology. Methods The study comprised five elements: (1) The incidence of HZ was estimated from immunocompetent adults ≥ 50 years of age not vaccinated with Zoster Vaccine Live who had incident HZ between 2011–2015. HZ was identified by International Classification of Diseases (ICD) codes from electronic health records (EHR) of 4.6 million Kaiser Permanente Southern California members; (2) Postherpetic neuralgia (PHN) was identified by validated survey and medical record review of laboratory-confirmed incident HZ cases recruited during 2012–2015 for HZ-related pain ≥ 90 days after initial HZ diagnosis; (3) HZ Ophthalmicus (HZO) with ocular complications was identified by ICD codes and keyword search in EHR among patients identified with HZO using a validated natural language processing algorithm; (4) The proportion of HZ-related non-PHN and non-HZO cutaneous, neurological or other complications was assessed by double abstraction of EHRs from a sample of 600 incident HZ cases; (5) Recurrent HZ was identified by having an HZ diagnosis with HZ antiviral medication ≥ 6 months after the most recent HZ diagnosis with HZ antiviral medication in a cohort initially diagnosed with HZ between 2007 and 2008 and followed through 2016. Results We identified 40,893 incident HZ cases with an overall incidence of 9.92 (95% confidence interval [CI]: 9.82–10.01) per 1000 person-years. The proportion of incident HZ cases with PHN and HZO with ocular involvement was 18.37% (95% CI: 14.90–21.84%) and 8.06% (95% CI: 7.80–8.32%), respectively. The proportion of cutaneous, neurological, and other complications was 7.20% (95% CI: 5.44–8.96%), 0.87% (95% CI: 0.79–0.95%), and 1.24% (95% CI: 1.15–1.33%), respectively. The incidence of recurrent HZ was 10.96/1000 person-years (95% CI: 10.18–11.79). Conclusion HZ is common among unvaccinated US adults ≥ 50 years of age, with PHN and HZO occurring most frequently among incident HZ cases. Funding GlaxoSmithKline Biologicals SA, GSK study identifier: HO-17-18378. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background In 2016, our academic medical center implemented the BioFire® FilmArray® Meningitis/Encephalitis Panel (MEP), which detects 14 viral, bacterial, and fungal pathogens. Institutional guidelines recommended the test be used in nonimmunocompromised patients age ≥2 years only if the cerebrospinal fluid (CSF) white blood cell (WBC) count was >10 cells/mm3. Methods We reviewed all MEP performed at our institution over 2 years (January 1, 2017 to December 31, 2018). We collected CSF WBC count, protein, and glucose; MEP results; CSF culture results; and demographics. We excluded children age <2 years, immunocompromised patients, those without a CSF WBC count, and duplicate tests during the same illness. Results Of 453 patients, 311 met inclusion criteria. The median age was 51, 51% male. Median CSF indices: WBC/mm3 = 4, protein = 57 mg/dL, glucose = 66 mg/dL. MEP positivity rate = 12% (37/311): viruses (29/37), bacteria (7/37), and fungi (1/37). Positive bacterial/fungal MEP results compared with CSF culture are summarized in Table 1. No clinically significant discordant negative MEP results occurred compared with CSF culture, cryptococcal antigen, or other viral PCR testing. Of the 311 patients, 184 (59%) had ≤10 CSF WBC/mm3. Of these, 4 had positive MEP results: 1 enterovirus, 1 human herpes virus 6 (HHV-6) and 2 varicella zoster virus (VZV). The HHV-6 was judged clinically insignificant. The 2 VZV cases had concomitant shingles and were already on acyclovir. No clinically significant MEP results occurred in 110/311 (35%) patients with ≤ 2 CSF WBC/mm3. Conclusion In nonimmunocompromised patients, age ≥ 2, with ≤ 10 CSF WBC/mm3 on lumbar puncture, positive MEP results were rare and the clinical significance of the 4 positives was debatable. A hard-stop restriction in this setting could have reduced overall use by up to 59% and resulted in significant cost savings. Lower CSF WBC/mm3 cut-offs could be considered and still improve MEP utilization. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]

Background Idiopathic CD4 Lymphocytopenia (ICL) is a rare immunodeficiency characterized by an absolute CD4+ T count of < 300 cells/µL, in absence of HIV-infection or any other known cause. Patients with ICL have an increased risk of opportunistic infections. The prevalence, natural history, and spectrum of Human Papillomaviruses (HPV) associated diseases in ICL patients are unknown. Methods ICL patients were enrolled in a prospective observational study (N = 90). Demographic, clinical, and immunologic data were analyzed by nonparametric Methods. Immunophenotyping was performed by flow cytometry. Results The median age of ICL patients was 48 years, 47% were women, and 92% were Caucasian. Sixty-five percent of patients had at least one opportunistic infection, with HPV being the most prevalent (34.4%), followed by cryptococcal disease (22%), shingles (15.5%), molluscum contagiosum (8.8%), Histoplasma capsulatum (4.4%), Mycobacterium avium complex (4.4%), and progressive multifocal encephalopathy (2.2%). HPV-related diseases were identified in 18 women and 13 men. ICL patients with HPV disease were younger compared with those without (median age 34 vs. 53.5 years, P < 0.0001). Nine (29%) had anogenital, 9 (29%) had a cutaneous disease (verruca plana, verrucous carcinoma, squamous cell carcinoma) while 13 (42%) had both anogenital and cutaneous disease. Patients with HPV-related disease were also more likely to have history of cryptococcal disease, shingles or molluscum (P = 0.036, P = 0.22 and 0.11, respectively). Thirteen patients had HPV-associated cancers: 7 both mucosal and skin and 3 either skin or mucosal malignancies. Patients with HPV-disease had lower CD4+ T cells (median CD4 70 vs. 114 cells/µL, P = 0.036). No differences were observed in the numbers of CD8+ T cells, B cells, NK cells, and levels of IgG between patients with and without HPV disease. Conclusion HPV-related disease represents the most common opportunistic infection in ICL patients. Patients with ICL and HPV disease are younger, have lower CD4s and high prevalence of HPV-associated malignancies. Therefore, for patients presenting early in life with severe HPV disease further immunological workup should be considered and for patients with ICL excessive screening for HPV-related malignancies should be a priority. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]