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Background: Hepatitis C virus (HCV) infection is a major public health burden, affecting over 4 million people. The Centers for Disease Control and Prevention and the US Preventive Services Task Force guidelines recommend screening everyone born between 1945 and 1965, but screening rates remain low.Objective: To determine whether bulk ordering and electronic messaging to patients improves guideline-based HCV screening rates.Design: A non-randomized controlled trial of 1024 adults from November 2016 to March 2017.Participants: Patients due for HCV screening with at least one primary care office visit in one of three primary care clinics and enrolled in the healthcare system's tethered personal health record (tPHR).Interventions: Control patients received normal care for HCV screening, consisting of passive HCV reminders to providers during face-to-face visits and passive HCV screening notification through the patient's tPHR. Intervention patients received normal care and also had HCV antibody tests ordered for them and customized messages sent through their tPHR inviting them to go directly to the lab for HCV screening over a 12-week period.Main Measures: Percentage/number of patients receiving HCV antibody tests during the intervention period. Percentage/number of intervention group patients receiving HCV screening with other blood work.Key Results: In the intervention group, 33% (168 of 514) completed HCV testing, compared with 19% (97 of 510) of controls (OR 1.7, 95% CI 1.2-2.1). Bulk lab ordering appeared to have a large impact while bulk messaging appeared to have a less significant role.Conclusions: Leveraging population analytics and bulk ordering in an electronic health record with bulk messaging to a tPHR directly engages patients in blood screening tests and can significantly improve completion. This methodology has a broad range of applications including many recommended screening or disease-specific testing. This bulk ordering and direct-to-patient messaging approach improves patient screening while decreasing provider/staff work.Trial Registration: MetroHealth IRB16-00776 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Background Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents. Methods We assembled a case series from 4 US academic medical centers where patients with adherence challenges were prescribed LEN subcutaneously every 26 weeks/CAB (+/− RPV) intramuscularly every 4 or 8 weeks. Descriptive statistics, including viral load (VL) outcomes, were summarized. Results All patients (n = 34: 76% male; 24% cis/trans female; 41% Black; 38% Latino/a; median age [range], 47 [28–75] years; 29% and 71% on CAB every 4 or 8 weeks) reported challenges adhering to oral ART. The reasons for using LEN/CAB with or without RPV were documented or suspected NNRTI mutations (n = 21, 59%), integrase mutations (n = 5, 15%), high VL (n = 6, 18%), or continued viremia on CAB/RPV alone (n = 4, 12%). Injection site reactions on LA LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 (32/34; 94%) were suppressed (VL <75 copies/mL) after starting LEN at a median (range) of 8 (4–16) weeks, with 16/34 (47%) suppressed at baseline. Conclusions In this case series of 34 patients on LEN/CAB, high rates of virologic suppression (94%) were observed. Reasons for using LEN/CAB included adherence challenges and underlying resistance, mostly to NNRTIs. These data support a clinical trial of LEN/CAB among persons with NNRTI resistance. [ABSTRACT FROM AUTHOR]

People infected with severe acute respiratory syndrome coronavirus 2 display a wide range of illness, from asymptomatic infection to severe respiratory distress resulting in death. We measured serum biomarkers in uninfected individuals and in individuals with mild, moderate, or critical coronavirus disease 2019 (COVID-19) disease. Levels of monocyte activation (soluble CD14 and fatty acid-binding protein 4) and inflammation (tumor necrosis factor receptors 1 and 2 [TNFR1 and TNFR2]) were increased in COVID-19 individuals, regardless of disease severity. Among patients with critical disease, individuals who recovered from COVID-19 had lower levels of TNFR1 and TNFR2 at hospital admission compared to these levels in patients with critical disease who ultimately died. [ABSTRACT FROM AUTHOR]

Background: Antibiotic-resistant gonorrhoea represents a global public health threat, and new therapies are needed. We aimed to compare the efficacy and safety of solithromycin, a fourth generation macrolide, with ceftriaxone plus azithromycin for the treatment of gonorrhoea.Methods: We did an open-label, multicentre, non-inferiority trial of patients aged 15 years or older with uncomplicated untreated genital gonorrhoea at two sites in Australia and one site in the USA. Patients were randomly assigned (1:1) to receive single dose oral solithromycin 1000 mg or intramuscular ceftriaxone 500 mg plus oral azithromycin 1000 mg. Neisseria gonorrhoeae cultures were obtained at baseline and test of cure (day 7 ± 2). The primary outcome was the proportion of patients with eradication of genital N gonorrhoeae based on culture at test of cure, assessed in the microbiological intention-to-treat (mITT) population, which included all randomly assigned patients who received any dose of study drug and had a positive genital culture for N gonorrhoeae at baseline. Non-inferiority of solithromycin was to be concluded if the lower limit of the 95% CI for the between-group differences was greater than -10%. Safety was analysed in all patients who received any dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02210325.Findings: Between Sept 3, 2014, and Aug 27, 2015, 262 patients were randomly assigned and 261 received treatment (130 in the solithromycin group and 131 in the ceftriaxone plus azithromycin group). In the mITT population, 99 (80%) of 123 patients in the solithromycin group and 109 (84%) of 129 patients in the ceftriaxone plus azithromycin group had N gonorrhoeae eradication at test of cure (difference -4·0%, 95% CI -13·6 to 5·5), thus solithromycin did not meet the criterion for non-inferiority at the prespecified -10% margin. The frequency of adverse events was higher in the solithromycin group than the ceftriaxone plus azithromycin group (69 [53%] of 130 patients vs 45 [34%] of 131 patients), the most common of which were diarrhoea (31 [24%] of 130 patients vs 20 [15%] of 131 patients), and nausea (27 [21%] of 130 patients vs 15 [11%] of 131 patients).Interpretation: Solithromycin as a single 1000 mg dose is not a suitable alternative to ceftriaxone plus azithromycin as first-line treatment for gonorrhoea. If insufficient duration of solithromycin exposure at the infection site in a subset of individuals was the reason for treatment failures, this might be adequately addressed with dose adjustment. However, any further trials with longer dosing need to consider the potential risk of gastrointestinal effects and liver enzyme elevations.Funding: Cempra Pharmaceuticals. [ABSTRACT FROM AUTHOR]

Background In this phase 2 study, we evaluated the efficacy and safety of oral gepotidacin, a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor, for the treatment of uncomplicated urogenital gonorrhea. Methods Adult participants with suspected urogenital gonorrhea were enrolled and completed baseline (day 1) and test-of-cure (days 4–8) visits. Pretreatment and posttreatment urogenital swabs were collected for Neisseria gonorrhoeae (NG) culture and susceptibility testing. Pharyngeal and rectal swab specimens were collected if there were known exposures. Participants were stratified by gender and randomized 1:1 to receive a 1500-mg or 3000-mg single oral dose of gepotidacin. Results The microbiologically evaluable population consisted of 69 participants, with NG isolated from 69 (100%) urogenital, 2 (3%) pharyngeal, and 3 (4%) rectal specimens. Microbiological eradication of NG was achieved by 97%, 95%, and 96% of participants (lower 1-sided exact 95% confidence interval bound, 85.1%, 84.7%, and 89.1%, respectively) for the 1500-mg, 3000-mg, and combined dose groups, respectively. Microbiological cure was achieved in 66/69 (96%) urogenital infections. All 3 failures were NG isolates that demonstrated the highest observed gepotidacin minimum inhibitory concentration of 1 µg/mL and a common gene mutation. At the pharyngeal and rectal sites, 1/2 and 3/3 NG isolates, respectively, demonstrated microbiological cure. There were no treatment-limiting adverse events for either dose. Conclusions This study demonstrated that single, oral doses of gepotidacin were ≥95% effective for bacterial eradication of NG in adult participants with uncomplicated urogenital gonorrhea. Clinical Trials Registration NCT02294682. [ABSTRACT FROM AUTHOR]

Background Heroin use may work synergistically with human immunodeficiency virus (HIV) infection to cause greater immune dysregulation than either factor alone. Unraveling how this affects end-organ disease is key as it may play a role in the excess mortality seen in people with HIV (PWH) who use heroin despite access to care and antiretroviral therapy. Methods This is a prospectively enrolled, cross-sectional study of adults with and without HIV who use and do not use heroin using (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to compare tissue-specific inflammation including aortic (target-to-background ratio [TBR]), splenic, and bone marrow (standardized uptake value [SUV]). Results A total of 120 participants were enrolled. The unadjusted mean difference in aortic TBR was 0.43 between HIV-positive [HIV+] heroin+ and HIV+ heroin-negative [heroin−] (P =.02); however, among HIV−, aortic TBR was similar regardless of heroin-use status. Further, HIV-by-heroin-use status interaction was significant (P =.02), indicating that the relationship between heroin use and higher aortic TBR depended on HIV status. On the other hand, both HIV (1.54 vs 1.68; P =.04, unadjusted estimated means for HIV+ vs HIV−) and heroin use were associated with lower bone marrow SUV, although the effect of heroin depended on sex (heroin-use-by-sex interaction, P =.03). HIV-by-heroin-use interaction was not significant for splenic or bone marrow SUV. Conclusions Aortic inflammation was greatest in PWH who use heroin, but paradoxically, bone marrow activity was the least in this group, suggesting complex and possibly divergent pathophysiology within these different end organs. [ABSTRACT FROM AUTHOR]

Background: Cancer is one of the most common comorbidities in men living with HIV (MLWH). However, little is known about the MLWH subgroups with the highest cancer burden to which cancer prevention efforts should be targeted. Because Medicaid is the most important source of insurance for MLWH, we evaluated the excess cancer prevalence in MLWH on Medicaid relative to their non‐HIV counterparts. Methods: In this cross‐sectional study using 2012 Medicaid Analytic eXtract data nationwide, we flagged the presence of HIV, 13 types of cancer, symptomatic HIV, and viral coinfections using codes from the International Classification of Diseases, Ninth Revision, Clinical Modification. The study population included individuals administratively noted to be of male sex (men), aged 18 to 64 years, with (n = 82,495) or without (n = 7,302,523) HIV. We developed log‐binomial models with cancer as the outcome stratified by symptomatic status, age, and race/ethnicity. Results: Cancer prevalence was higher in MLWH than in men without HIV (adjusted prevalence ratio [APR], 1.84; 95% confidence interval [CI], 1.78‐1.90) and was higher among those with symptomatic HIV (APR, 2.74; 95% CI, 2.52‐2.97) than among those with asymptomatic HIV (APR, 1.73; 95% CI, 1.67‐1.79). The highest APRs were observed for anal cancer in younger men, both in the symptomatic and asymptomatic groups: APR, 312.97; 95% CI, 210.27‐465.84, and APR, 482.26; 95% CI, 390.67‐595.32, respectively. In race/ethnicity strata, the highest APRs were among Hispanic men for anal cancer (APR, 198.53; 95% CI, 144.54‐272.68) and for lymphoma (APR, 9.10; 95% CI, 7.80‐10.63). Conclusions: Given the Medicaid program's role in insuring MLWH, the current findings highlight the importance of the program's efforts to promote healthy behaviors and vaccination against human papillomavirus in all children and adolescents and to provide individualized cancer screening for MLWH. The burden of cancer in men living with HIV (MLWH) on Medicaid is substantial. Given the role of the Medicaid program in insuring MLWH, the findings highlight the importance of the program's efforts to promote healthy behaviors and vaccine against human papillomavirus in all children and adolescents and to provide individualized cancer screening for MLWH. [ABSTRACT FROM AUTHOR]

Background: Altered gut integrity is central to HIV-related immune activation. Opioids may promote similar changes in gut permeability and/or increase systemic inflammation, potentially augmenting processes already occurring in people with HIV (PWH). Setting: Urban hospital systems in Cleveland, Ohio, and surrounding communities. Methods: This is a prospectively enrolled, cross-sectional study including people with and without HIV using heroin and people with and without HIV who have never used heroin, matched by age, sex, and CD4+ T-cell count (PWH only) to compare markers of gut integrity, microbial translocation, systemic inflammation, and immune activation. Results: A total of 100 participants were enrolled. Active heroin use was associated with higher concentrations of lipopolysaccharide-binding protein (LBP), beta-D-glucan (BDG), high-sensitivity C-reactive protein (hsCRP), soluble tumor necrosis factor-[alpha]-receptors I and II, soluble CD163, inflammatory monocytes, and activated CD4+ lymphocytes in adjusted models. HIV status tended to modify the effect between heroin use and LBP, BDG, hsCRP, patrolling monocytes, and activated CD4+ lymphocytes (P < 0.15 for interactions); however, it was not as expected. The effect of heroin on these markers (except patrolling monocytes) was greatest among those without HIV rather than among those with HIV. Conclusions: Heroin use is associated with heightened microbial translocation, systemic inflammation, and immune activation. Concurrent HIV infection in virologically suppressed individuals does not seem to substantially worsen the effects heroin has on these markers. [ABSTRACT FROM AUTHOR]

The incidence of syphilis infections is on the rise, particularly among African American men and men who have sex with men, and it is reaching epidemic levels in these communities throughout the United States. Although syphilis is relatively inexpensive to treat and cure and is a predictor for HIV incidence among men and transgender women who have sex with men, rates of co-screening for syphilis are low in the emergency department setting, with a dearth of literature on this topic since the 1990s and early 2000s. In this case study, we describe an operational model for routine syphilis screening implemented in June 2017 at the University Hospitals Cleveland Medical Center in Cleveland, Ohio. We describe the advantages of screening using a reverse testing algorithm rather than the traditional method and the necessity of partnering with the Cleveland Department of Public Health for both diagnostic and follow-up logistics. [ABSTRACT FROM AUTHOR]

Collaborative care can treat depression in HIV but existing studies have been limited by excluding patients with acute or severe depression. The purpose of this analysis is to determine if real-world implementation of collaborative care in HIV is associated with improvement in depression, and to identify correlates of depression outcomes. Collaborative care was implemented as part of a large practice transformation initiative. Change in depression, measured by PHQ-9 score, at baseline compared to 12 months post-enrollment was the outcome, which was operationalized as remission, response, and neither response nor remission. Bivariate and multivariate associations were assessed between several variables at baseline and the outcome. Out of 416, 99 (23.79%) patients remitted and 89 (21.39%) responded (without remission). In the bivariate analysis having a documented psychiatric comorbidity was associated with low remission [31 (16.58%)]; p = 0.008. Having generalized anxiety disorder was associated with low remission [18 (15.00%)] and response rates [26 (21.67%)]; p = 0.022. Having a substance use disorder (alcohol, cocaine, or amphetamine) – was associated with poor remission [29 (16.67%)] and response [33 (18.97%)]; p = 0.004. Social isolation was correlated with lower response and remission rates (p = 0.0022). In the multivariate analysis older age was associated with higher remission rates (OR: 1.10; 95% CI: 1.005–1.194) whereas being a Medicaid beneficiary (OR: 0.652; 95% CI: 1.123–2.797), having comorbid generalized anxiety disorder (OR: 0.267; 95% CI: 0.122–0.584) or a stimulant use disorder (cocaine [OR: 0.413; 95% CI: 0.222–0.926] or amphetamines [OR: 0.185; 95% CI: 0.037–0.766]), was associated with lower remission rates. We found that depression improved in our study subjects. We identified several modifiable correlates of depression outcomes. [ABSTRACT FROM AUTHOR]

Background. The burden of HIV-related stigma is associated with disparities in linkage to HIV care and viral suppression. The Positive Peers smartphone application aims to provide young people living with HIV with a supportive virtual community to counteract perceived stigma and better manage their illness. Method. A mixed-methods study that included a prospective survey and in-depth interviewing was conducted with young adults living with HIV, aged 13 to 34 years (n = 128). As part of a larger study, participants used the Positive Peers mobile application and reported demographic data, perceived stigma, and other psychosocial variables at enrollment, 6 months, and 12 months (n = 128). Select participants (n = 15) described their experiences in audio-recorded qualitative interviews. Verbatim transcripts were analyzed for potential themes and patterns. Results. A longitudinal multivariate model was developed to assess changes in stigma over the study period, overall, and with respect to participant characteristics. Baseline and 6-month stigma scores were higher for White and Other ethnicity persons relative to Black participants. At the 12-month time point, no statistical differences in stigma scores based on ethnicity were apparent. Interviews revealed Positive Peers as a nondiscriminatory community that offered a sense of belonging that appeared to have a restorative effect on negative self-image. Conclusions. Positive Peers provides a protected virtual space where young people living with HIV can converge in the common desire to support similar others. Mobile health applications that offer peer interaction may provide a persistent sense of belonging that neutralizes internalized stigmas in addition to benefits derived from application activity. [ABSTRACT FROM AUTHOR]

Women received <5% of all US pre-exposure prophylaxis (PrEP) prescriptions in 2016. Among 351 heterosexual women surveyed in Cleveland, Ohio, 14.5% were aware of PrEP, 20.5% knew where to access PrEP, 75.9% were willing to try PrEP, and 50.9% expressed interest in more information. [ABSTRACT FROM AUTHOR]

Long-term survival of people living with HIV (PLWH) is associated with the development of co-morbid conditions and need for symptom management and other efforts to enhance quality of life. We conducted a longitudinal, randomized trial over 36 months to evaluate the effect of a community-based navigator intervention to provide early palliative care to 179 PLWH and other chronic conditions. Outcomes included quality of life, symptom management, coping ability, social support, self-management, and completion of advance directives. Data were analyzed using SAS mixed effects model repeat measurement. Our navigator program showed variable improvement over time of three outcome variables, self-blame, symptom distress, and HIV self-management. However, the program did not improve overall quality of life, social support, or completion of advance directives. [ABSTRACT FROM AUTHOR]

The Chlamydia pneumoniae CopN protein is a member of the YopN/TyeA/InvE/MxiC family of secreted proteins that function to regulate the secretion of type III secretion system (T3SS) translocator and effector proteins. In this study, the Scc1 (CP0432) and Scc4 (CP0033) proteins of C. pneumoniae AR-39 were demonstrated to function together as a type III secretion chaperone that binds to an N-terminal region of CopN. The Scc1/Scc4 chaperone promoted the efficient secretion of CopN via a heterologous T3SS, whereas, the Scc3 chaperone, which binds to a C-terminal region of CopN, reduced CopN secretion. [ABSTRACT FROM AUTHOR]

Background: Although routine HIV testing is recommended for jails, little empirical data exist describing newly diagnosed individuals in this setting. Methods: Client-level data (CLD) are available on a subset of individuals served in EnhanceLink, for the nine of the 10 sites who enrolled newly diagnosed persons in the client level evaluation. In addition to information about time of diagnosis, we analyzed data on initial CD4 count, use of antiretroviral therapy (ART), and linkage to care post discharge. Baseline data from newly diagnosed persons were compared to data from persons whose diagnoses predated jail admission. Results: CLD were available for 58 newly diagnosed and 708 previously diagnosed individuals enrolled between 9/08 and 3/ 11. Those newly diagnosed had a significantly younger median age (34 years) when compared to those previously diagnosed (41 years). In the 30 days prior to incarceration, 11% of those newly diagnosed reported injection drug use and 29% reported unprotected anal intercourse. Median CD4 count at diagnosis was 432 cells/mL (range: 22-1,453 cells/mL). A minority (21%, N = 12) of new diagnoses started antiretroviral treatment (ART) before release; 74% have evidence of linkage to community services. Conclusion: Preliminary results from a cross-sectional analysis of this cohort suggest testing in jails finds individuals early on in disease progression. Most HIV+ detainees did not start ART in jail; therefore screening may not increase pharmacy costs for jails. Detainees newly diagnosed with HIV in jails can be effectively linked to community resources. Jail-based HIV testing should be a cornerstone of "test and treat" strategies. [ABSTRACT FROM AUTHOR]

Background In 2016, MetroHealth System (MHS) launched the FOCUS (Frontlines of Communities in the United States) project to routinize HIV testing in the emergency department (ED). Before 2016, clinical decision support (CDS) for HIV testing was not in place, nor was there a policy to support the importance of opt-out, nontargeted screening. The purpose of this study was to outline the progress of HIV testing after the integration of CDS, as well as describe the implementation challenges, and how certain events impacted HIV testing. Methods HIV testing data from MHS EDs were collected from October 1, 2015 to March 31, 2019 and graphed into a run chart. The dataset was mapped with the following events: project start date, ED testing begins (without CDS), CDS implementation, the staffing of the ED Testing Coordinator (EDTC), and optimization of CDS (Figure 1). To determine whether observed variation in the dataset is due to random or special cause variation, these run chart rules were applied: Run, Shift (Figure 2), and Trend. Results There were 42 data points and 4 runs. With 42 points, the lower limit of runs was 16 and the upper limit of runs was 28. This signals that one or more special cause variations were present. A total of three distinct shifts were observed indicating special cause variation. The run chart did not include any downward or upward trends. Testing increased as much as 3971% (7 tests in October 2015 vs. 285 tests in March 2018). Conclusion HIV testing increased from 7 tests to 86 tests (Shift 1). This coincided with establishment of an ED testing policy in April 2016. Testing increased to 266 tests in October 2016 (Shift 2). This directly related to implementation of CDS in the ED. December 2017 displayed the lowest testing with 117 tests. This was due to lack of policy awareness, and to the rarely-visited location of the HIV screening tool during the triage process. Staff was re-educated and the HIV screening tool was moved to a more visible location. This resulted in 227 tests in February 2018, and was followed by the highest testing month with 285 tests (Shift 3). Continued challenges prohibit sustained upward trends in ED testing. A control chart may be the appropriate next step to identify new control limits Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background In 2016, The MetroHealth System began enhanced hepatitis C (HCV) screening through decision support, coupled with linkage of newly diagnosed patients to specialty care by a Linkage to Care coordinator (LTCC). Prior to this, patients were notified of their HCV diagnosis by a provider and given a referral to a specialist. We hypothesized that an LTCC would shorten time from HCV diagnosis to HCV treatment. Methods Patients newly diagnosed with HCV between June 1, 2015 and December 31, 2015 (Pre-LTCC), were compared with patients newly diagnosed between January 1, 2016 and March 31, 2017 (Post-LTCC). Patients who were HCV RNA negative were excluded. The time between diagnosis and linkage, linkage and treatment start date, and diagnosis and treatment start date for each population were compared using unpaired t -tests. Results 125 newly diagnosed patients were identified in the Pre-LTCC population. 83 (66%) were linked to specialty care and 27 (22%) received HCV treatment. 446 newly diagnosed patients were identified in the Post-LTCC population. 211 (47%) were linked to specialty care and 70 (16%) HCV positive persons were treated. No significant difference was noted between the groups in days between diagnosis and specialty care linkage (Pre-LTCC mean = 120 days; Post-LTCC mean = 102 days). The time from linkage to treatment was significantly longer in Pre-LTCC (260 days) than Post-LTCC persons (152 days), P < 0.05. The average time from diagnosis to treatment in pre-LTCC persons was also significantly longer than in Post-LTCC (332 days vs. 237 days, P < 0.05) (See Table). Conclusion We demonstrate that post-implementation of an LTCC program for HCV, the time between diagnosis and treatment of HCV was significantly reduced. This reduction, however, did not seem to be due to faster linkage to specialty care. A limitation of the study is that differences in HCV care (insurance restrictions, availability of new regimens) between the pre-LTCC and post-LTCC period were not considered. Although the linkage rate in the post-LTCC period was lower, some patients in post-LTCC may still be awaiting linkage. While there was an observed reduction in time between linkage and treatment, further research is needed to determine the causes of this reduction. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]