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Background: Patients presenting for emergency department (ED) evaluation may be appropriate for treatment with monoclonal antibodies for mild to moderate COVID-19. While many sites have implemented infusion centers for these agents, EDs will continue to evaluate these patients where appropriate identification and efficient infusion of eligible patients is critical. Objectives: Patients receiving bamlanivimab in the EDs of an academic medical center are described. The primary objective was to describe operational metrics and secondary objectives reported clinical outcomes. Methods: Patients receiving bamlanivimab and discharged from the ED were included from November 16, 2020 to January 16, 2021 in the retrospective, observational cohort. Primary outcome was adherence to institutional criteria. Secondary outcomes included ED visit metrics, clinical characteristics, and return visits within 30 days. Risk factors for return visits were assessed with regression. Results: One hundred nineteen patients were included. Most (71%) were diagnosed with COVID-19 during the ED visit and median symptom duration was 3(IQR 2-5) days. Median number of risk factors for progression to severe disease was 2 (IQR 1-2). Thirty percent had a documented abnormal chest x-ray. Institutional criteria adherence was 99.2%. Median time from ED room to bamlanivimab was 4 (IQR 3.1-5.2) hours. Thirty patients had return visit within 30 days; 19 were COVID-19 related. Two multivariable regression models were analyzed for COVID-19 related return visit. Characteristics on ED presentation were considered in Model I: male gender (OR 3.01[0.97-9.31]), age (per 10 years) (OR 1.49[1.05-2.12]), African-American race (OR 3.46[1.09-11.06]), and symptom duration (per day) (OR 1.34[1.05-1.73]). Model II included labs and imaging acquired in ED. In Model II, age (per 10 years) (OR 1.52[1.07-2.16]) and abnormal CXR (OR 5.74[1.95-16.9]) were associated with COVID-19 related return visits. Conclusions: Administration of bamlanivimab to ED patients can be done efficiently, with the potential to reduce COVID-19 related return visits. Age and abnormal imaging were independent predictors of COVID-19 return visits.

Background: Alterations in gut microbiota and blood metabolomic profiles have been implicated in HIV infection and cardiovascular disease. However, it remains unclear whether alterations in gut microbiota may contribute to disrupted host blood metabolomic profiles in relation to atherosclerosis, especially in the context of HIV infection. Methods: We analyzed cross-sectional associations between gut microbiota features and carotid artery plaque in 361 women with or at high risk of HIV (67% HIV+), and further integrated plaque-associated microbial features with plasma lipidomic/metabolomic profiles. Furthermore, in 737 women and men, we examined prospective associations of baseline gut bacteria-associated lipidomic and metabolomic profiles with incident carotid artery plaque over 7-year follow-up. Results: We found 2 potentially pathogenic bacteria, Fusobacterium and Proteus , were associated with carotid artery plaque; while the beneficial butyrate producer Odoribacter was inversely associated with plaque. Fusobacterium and Proteus were associated with multiple lipids/metabolites which were clustered into 8 modules in network. A module comprised of 9 lysophosphatidylcholines and lysophosphatidylethanolamines and a module comprised of 9 diglycerides were associated with increased risk of carotid artery plaque (risk ratio [95% CI], 1.34 [1.09–1.64] and 1.24 [1.02–1.51] per SD increment, respectively). Functional analyses identified bacterial enzymes in lipid metabolism associated with these plasma lipids. In particular, phospholipase A1 and A2 are the key enzymes in the reactions producing lysophosphatidylcholines and lysophosphatidylethanolamines. Conclusions: Among individuals with or at high risk of HIV infection, we identified altered gut microbiota and related functional capacities in the lipid metabolism associated with disrupted plasma lipidomic profiles and carotid artery atherosclerosis.

Background Inflammasome activation is increased in people with human immunodeficiency virus (PWH), but its relationship with coronary plaque is poorly understood in this setting. Methods In a large human immunodeficiency virus cardiovascular prevention cohort, relationships between caspase-1, interleukin (IL)-1β, and IL-18 and coronary plaque indices were assessed by multivariate logistic regression. Results Higher IL-18 and IL-1β were associated with Leaman score, an integrative measure of plaque burden and composition. Conclusions As Leaman score >5 is associated with cardiovascular events in the general population, future work is needed to determine how the inflammasome relates to events and whether strategies to reduce its activation affect events or plaque progression among PWH.

Background Many people at risk for sexually transmitted infections (STIs) utilize the emergency department (ED) for evaluation and treatment of STI-related complaints. Syphilis testing rates in the ED have historically been low. Following the implementation of a joint ED and Infectious Disease (ID) multidisciplinary quality improvement initiative designed to increase syphilis testing in this setting, we sought to evaluate the demographics and clinical outcomes for patients diagnosed with early syphilis in the ED. Methods A retrospective chart review of patients with positive syphilis test results from ED encounters at the Ohio State University Wexner Medical Center East Hospital between 1 January 2019 and 31 December 2021 was performed. Demographic and clinical information was obtained for patients diagnosed with early syphilis (primary, secondary or early latent syphilis). Results Since 2019, we have observed a significant increase early syphilis cases identified in our ED despite stable rates of testing (Figure 1). There were 55 cases of early syphilis, 3 with neurosyphilis (NS) at the time of diagnosis (Figure 2). Most cases were men (38/55; 69%), Black/African American (44/55; 80%), and symptomatic (48/55; 87%). Nine of 55 patients (16%) had HIV co-infection, 2 were new diagnoses at time of syphilis diagnosis. Most patients (44/55; 80%) completed appropriate treatment. Of the symptomatic patients, 17/45 (37%) received presumptive treatment in the ED (3 cases of NS excluded). Of those who received treatment after discharge from the ED, the median time to treatment completion was 3 days (range 0-30), with 11/24 (46%) returning to the ED for treatment. Figure 1.Figure 2. Conclusion As a result of a collaborative ED/ID STI testing initiative established at our institution, we have observed a significant increase in the number of symptomatic early syphilis cases identified in our ED between 2019 and 2021, with most patients completing treatment in a timely manner. This data show that the ED is an important and feasible setting for syphilis diagnosis and treatment when appropriate support systems are in place, including established communications with ID colleagues. Disclosures Carlos Malvestutto, MD MPH, Gilead Sciences: Advisor/Consultant|Viiv Healthcare: Advisor/Consultant Susan L. Koletar, MD, Gilead Sciences: Grant/Research Support.

Treatment with monoclonal antibodies has been shown to significantly reduce the risk of hospitalization and disease progression among high-risk patients with coronavirus disease 2019 (COVID-19). Pregnant individuals were excluded from the original trials. In this single-center retrospective cohort study, we evaluated whether monoclonal antibody treatment in pregnant individuals is associated with decreased risk of hospitalization. Outcomes of patients who received the treatment were compared with those who were eligible but did not receive the treatment. Analyses were stratified by vaccination status. Unvaccinated pregnant patients with mild or moderate COVID-19 who received outpatient monoclonal antibodies were less likely to be admitted to the hospital (4.2% vs 15.7%, odds ratio 0.24, 95% CI 0.07-0.74), whereas among vaccinated patients, the treatment was not associated with a lower rate of hospitalization (2.3% vs 0%, P=.99).

REPRIEVE, the Randomized Trial to Prevent Vascular Events in HIV, is a multicenter, primary prevention trial evaluating whether a statin can prevent major cardiovascular events in people with HIV. REPRIEVE is conducted at100 clinical research sites (CRSs) globally. Detailed, comprehensive, and novel methods for evaluating and communicating CRS performance are required to ensure trial integrity and data quality. In this analysis we describe a comprehensive multidimensional methodology for evaluating CRS performance.The REPRIEVE Data Coordinating and Clinical Coordinating Centers developed a robust system for evaluation of and communication with CRSs, designed to identify potential issues and obstacles to performance, provide real-time technical support, and make recommendations for process improvements to facilitate efficient trial execution. We describe these systems and evaluate their impact on participant retention, data management, and specimen management from 2019 to 2022, corresponding to the period from end of recruitment to present. This evaluation was based on pre-defined metrics, regular reviews, and bidirectional communication.Participant retention, data management, and specimen management all remained steady over the three-year period, although metrics varied by country of enrollment. Targeted messaging relating to certain performance metrics was effective.Site performance is vital to ensure trial integrity and achievement of key trial goals. This analysis demonstrates that utilization of a comprehensive approach allows for a thorough evaluation of CRS performance, facilitates data and specimen management, and enhances participant retention. Our approach may serve as a guidepost for maximizing future large-scale clinical trials' operational success and scientific rigor.gov Identifier: NCT02344290.

Background Cytomegalovirus (CMV) infection is thought to result in increased immune activation in people with human immunodeficiency virus (HIV, PWH). Although some data have linked asymptomatic CMV infection to cardiovascular disease among PWH, it remains unknown whether CMV is associated with increased or high-risk coronary plaque. Methods The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) enrolled PWH aged 40–75 years on stable antiretroviral therapy (ART) with low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk. Among a subset of US REPRIEVE participants, coronary plaque was assessed by coronary computed tomography angiography. Here, we assessed the relationship between CMV immunoglobulin G (IgG) titer and (1) levels of immune activation, (2) inflammatory biomarkers, and (3) coronary plaque phenotypes at study entry. Results Of 672 participants, mean age was 51 years, 83% were men, median ASCVD risk score was 4.5%, and 66% had current CD4+ T-cell count ≥500 cells/mm3. Higher CMV IgG quartile group was associated with older age and lower current and nadir CD4+ T-cell counts. CMV IgG titer was associated with specific inflammatory biomarkers (sCD163, MCP-1, interleukin [IL]-6, hsCRP) in univariate analysis, but not after controlling for HIV-specific factors. In contrast, CMV IgG titer was not associated with coronary artery disease indexes, including presence of plaque, coronary artery calcium (CAC) score >0, vulnerable plaque presence, or Leaman score >5. Conclusions No meaningful association was seen between CMV IgG titer and coronary artery disease indexes among ART-treated PWH at study enrollment. Longitudinal assessments in REPRIEVE will determine the relationship of CMV IgG titer to plaque progression and cardiovascular events. Clinical Trials Registration NCT02344290.

This study reports that focused collaboration between infectious diseases and emergency medicine providers results in increased identification of patients with syphilis and HIV in the emergency department., Background Sexually transmitted infections (STIs) are a common reason for evaluation in the emergency department (ED). Given the overlapping risk factors for STIs, patients screened for gonorrhea and chlamydia should be tested for syphilis and HIV. Syphilis and HIV testing rates in the ED have been reported to be low. The study objective was to examine whether collaboration between emergency medicine (EM) and infectious disease (ID) providers improved syphilis and HIV testing in the ED. Methods A multidisciplinary team of EM and ID providers was formed to identify and address barriers to syphilis and HIV testing in the ED. Syphilis, HIV, chlamydia, and gonorrhea testing and infection rates were calculated and compared during 2 time periods: preintervention (January 1, 2012–December 30, 2017) and postintervention (November 1, 2018–November 30, 2019). We also extracted clinical and laboratory data from patients with positive syphilis and HIV results during the study period. Results The most commonly cited barrier to syphilis and HIV testing was concern about follow-up of positive results. Compared with the preintervention period, syphilis and HIV testing rates increased significantly in the postintervention period (incidence rate ratios, 30.70 [P < 0.0001] and 28.99 [P < 0.0001] for syphilis and HIV, respectively). The postintervention period was also associated with a significant increase in the identification of patients with positive syphilis and HIV results (incidence rate ratios, 7.02 [P < 0.0001] and 2.34 [P = 0.03], respectively). Conclusions Collaboration between EM and ID providers resulted in a significant increase in syphilis and HIV testing and diagnosis in the ED.

BACKGROUND: People who inject drugs (PWID) in rural areas of the United States have had limited access to syringe service programs (SSP). Rural SSP have recently surged, but accompanying research is lacking about PWID utilization, barriers, and preferences for SSP design and how those preferences vary by gender. METHODS: Interviewer-administered surveys elicited information about utilization, barriers, and preferences for SSP design from 234 PWID recruited using respondent-driven sampling in Appalachian, Kentucky. Gender differences among reported barriers to utilizing SSP and preferences for program design were explored using Mantel-Haenszel chi-square tests. RESULTS: Overall, 49% of PWID had ever utilized an SSP. The most common reasons for not utilizing an SSP were lack of awareness (23%), fear of being seen or disclosing drug use (19%), and lack of need (19%). The most preferred SSP design was located within a health department (74%) and operating during afternoon hours (66%). Men were more likely than women to prefer SSP in health departments (80% vs. 65%, p = 0.01), while more women than men preferred staffing by health department personnel (62% vs. 46%, p = 0.02). Women were less likely to favor evening hours (55% vs. 70%, p = 0.02). Fewer women wanted SSP nurses (78% vs. 90%, p = 0.01), social workers (11% vs. 24%, p = 0.01), or people who use drugs (20% vs 34%, p = 0.02) to staff SSP. CONCLUSIONS: Despite recent scale-up, SSP in Appalachia remain under-utilized. PWID were open to a range of options for SSP design and staffing, though there were variations by gender. Implementation research that identifies best strategies for tailored SSP scale-up in rural settings should be considered.

Limited data are available regarding asymptomatic COVID-19 among people with HIV (PWH). Data on a representative subset of PWH enrolled in Randomized Trial to Prevent Vascular Events in HIV, a global clinical trial, are presented here.Randomized Trial to Prevent Vascular Events in HIV is an atherosclerotic cardiovascular disease prevention trial among 7770 PWH on antiretroviral therapy. Beginning April 2020, targeted data on coronavirus disease 2019 (COVID-19) diagnosis and symptoms were collected during routine trial visits. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was defined as either COVID-19 clinical diagnosis or presence of SARS-CoV-2 Immunoglobulin G (IgG) or Immunoglobulin A (IgA) receptor binding domain protein (antispike) antibodies in the absence of prior COVID-19 vaccine.The group (N = 2464) had a median age 53 years, 35% female sex, 47% Black or African American race, median CD4 count 649 c/mm 3 , and 97% with HIV VL400 cp/m. SARS-CoV-2 infection occurred in 318 persons (13%): 58 with clinical diagnosis and 260 with detectable antibodies. Of these PWH, 304 completed symptom questionnaires: 121 (40%) reported symptoms, but 183 (60%) were asymptomatic. PWH with asymptomatic SARS-CoV-2 infection were more likely to be from low-income or middle-income regions, of Black or African American race, older in age, and with higher atherosclerotic cardiovascular disease risk score. Symptomatic COVID was more common with obesity, metabolic syndrome, and low HDL levels. CD4 counts and HIV viral suppression rates were similar among PWH with symptomatic vs. asymptomatic COVID.Asymptomatic SARS-CoV-2 infection is common among antiretroviral therapy-treated PWH globally. We determined that 60% of infections in PWH were asymptomatic. HIV clinicians must remain vigilant about COVID-19 testing among PWH to identify asymptomatic cases.

Little is known regarding coronavirus disease 2019 (COVID-19) vaccination rates in people with HIV (PWH), a vulnerable population with significant morbidity from COVID-19. We assessed COVID-19 vaccination rates among 6952 PWH in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) compared to region- and country-specific vaccination data. The global probability of COVID-19 vaccination through end of July 2021 was 55% among REPRIEVE participants with rates varying substantially by Global Burden of Disease (GBD) superregion. Among PWH, factors associated with COVID-19 vaccination included residence in high-income regions, age, white race, male sex, body mass index, and higher cardiovascular risk. Clinical Trials Registration. NCT02344290.

ImportanceThe antiviral activity and efficacy of anti-SARS-CoV-2 monoclonal antibody (mAb) therapies to accelerate recovery from COVID-19 is important to define.ObjectiveTo determine safety and efficacy of the mAb bamlanivimab to reduce nasopharyngeal (NP) SARS-CoV-2 RNA levels and symptom duration.DesignACTIV-2/A5401 is a randomized, blinded, placebo-controlled platform trial. Two dose cohorts were enrolled between August 19 and November 17, 2020 for phase 2 evaluation: in the first, participants were randomized 1:1 to bamlanivimab 7000 mg versus placebo, and in the second to bamlanivimab 700 mg versus placebo. Randomization was stratified by time from symptom onset (≤ or >5 days) and risk of progression to severe COVID-19 (“higher” vs “lower”).SettingMulticenter trial conducted at U.S. sites.ParticipantsNon-hospitalized adults ≥18 years of age with positive SARS-CoV-2 antigen or nucleic acid test within 7 days, ≤10 days of COVID-19 symptoms, and with oxygen saturation ≥92% within 48 hours prior to study entry.InterventionSingle infusion of bamlanivimab (7000 or 700 mg) or placebo.Main Outcomes and MeasuresDetection of NP SARS-CoV-2 RNA at days 3, 7, 14, 21, and 28, time to improvement of all of 13 targeted COVID-19 symptoms by daily self-assessment through day 28, and grade 3 or higher treatment emergent adverse events (TEAEs) through day 28. Secondary measures included quantitative NP SARS-CoV-2 RNA, all-cause hospitalizations and deaths (composite), area under the curve of symptom scores from day 0 through day 28, plasma bamlanivimab concentrations, plasma and serum inflammatory biomarkers, and safety through week 24.ResultsNinety-four participants were enrolled to the 7000 mg cohort and 223 to the 700 mg cohort and initiated study intervention. The proportion meeting protocol criteria for “higher” risk for COVID-19 progression was 42% and 51% for the 7000 and 700 mg cohort, respectively. Median time from symptom onset at study entry for both cohorts was 6 days. There was no difference in the proportion with undetectable NP SARS-CoV-2 RNA at any post-treatment timepoints (risk ratio compared to placebo, 0.82-1.05 for 7000 mg dose [overall p=0.88] and 0.81-1.21 for 700 mg dose [overall p=0.49]), time to symptom improvement (median of 21 vs 18.5 days, p=0.97, for 7000 mg bamlanivimab vs placebo and 24 vs 20.5 days, p=0.08, for 700 mg bamlanivimab vs placebo), or grade 3+ TEAEs with either dose compared to placebo. Median NP SARS-CoV-2 RNA levels were lower at day 3 and C-reactive protein, ferritin, and fibrinogen levels significantly reduced at days 7 and 14 for bamlanivimab 700 mg compared to placebo, with similar trends observed for bamlanivimab 7000 mg. Viral decay modeling supported more rapid decay with bamlanivimab compared to placebo.Conclusions and RelevanceTreatment with bamlanivimab 7000 mg and 700 mg was safe and compared to placebo led to more rapid reductions in NP SARS-CoV-2 RNA and inflammatory biomarkers, but did not decrease time to symptom improvement. The clinical utility of mAbs for outcomes other than hospitalizations and deaths is uncertain.Trial RegistrationClinicalTrials.gov Identifier: NCT04518410KEY POINTSQuestionWhat is the safety and efficacy of bamlanivimab monoclonal antibody (mAb) treatment for mild to moderate COVID-19?FindingsIn this randomized, placebo-controlled phase 2 trial of 317 non-hospitalized adults with COVID-19, there was no relationship between symptoms or disease progression risk and nasopharyngeal (NP) virus shedding. Bamlanivimab was safe and reduced NP SARS-CoV-2 RNA levels and inflammatory biomarker levels more than placebo, but did not shorten symptom duration.MeaningNasal virus shedding was not associated with symptoms or baseline risk factors for severe COVID-19. Bamlanivimab, which has been associated with reduced hospitalizations in high-risk individuals, demonstrated antiviral activity with early post-treatment NP sampling but did not accelerate symptom improvement. The clinical utility of bamlanivimab for outcomes other than hospitalizations and deaths, including longer-term outcomes, is uncertain.

Background Emerging data demonstrate that the use of integrase inhibitor (INSTI)-based antiretroviral treatment (ART) is associated with increased weight, but the cardiometabolic health consequences of increased weight remains poorly understood. Methods This analysis examined INSTI use (>6 months) at entry among REPRIEVE participants enrolled in High Income and Latin America/Caribbean Global Burden of Disease regions. Primary analyses used linear and logistic regression; secondary analyses used quantile regression to examine differences across the full data distribution. Characteristics of those with and without INSTI use were balanced using inverse probability of treatment weighting. Results Among 4500 REPRIEVE participants, 1848 were on an INSTI-based regimen at entry for an average of 2.1 ± 1.8 years. Integrase inhibitor use (vs no INSTI use) was associated with higher odds of obesity (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.4–1.9) and higher mean body mass index ([BMI] +1.5kg/m2; 95% CI, 1.0–1.9) and waist circumference (+3.6cm; 95% CI, 2.6–4.6). Differences in weight related to INSTI use were greater in the upper tails of the distribution (+3.1kg/m2 [95% CI, 1.9–4.4] at the 90th centile vs +0.7kg/m2 [95% CI, 0.2–1.2] at the 50th centile) and among women and nonwhite participants, with sex and race having an additive effect on BMI. Conversely, INSTI use was not associated with differences in glucose, low-density lipoprotein cholesterol, or higher odds of metabolic syndrome or hypertension. Conclusions Differences in weight and waist circumference associated with INSTI use are (1) not uniform across people with human immunodeficiency virus, (2) greatest among women and nonwhites, and (3) concentrated at the upper tails of weight distribution. These data identify at-risk subgroups for whom long-term cardiovascular disease outcomes should be carefully assessed., INSTI-based regimens are associated with higher weight but not with increased cardiovascular risk for most INSTI users. Differences in weight are not uniform across PWH, and specific subgroups of INSTI users should be monitored for long-term CVD outcomes.

Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) blunts the broad inflammatory response induced by damage-associated molecular patterns via binding to extracellular high mobility group box 1 and heat shock proteins, as well as regulating the downstream Siglec10-Src homology 2 domain–containing phosphatase 1 pathway. A recent randomized phase III trial evaluating CD24Fc for patients with severe COVID-19 (SAC-COVID; NCT04317040) demonstrated encouraging clinical efficacy. Methods Using a systems analytical approach, we studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial to discern the impact of CD24Fc treatment on immune homeostasis. We performed high dimensional spectral flow cytometry and measured the levels of a broad array of cytokines and chemokines to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19. Results Twenty-two patients were enrolled, and the clinical characteristics from the CD24Fc vs. placebo groups were matched. Using high-content spectral flow cytometry and network-level analysis, we found that patients with severe COVID-19 had systemic hyper-activation of multiple cellular compartments, including CD8+ T cells, CD4+ T cells, and CD56+ natural killer cells. Treatment with CD24Fc blunted this systemic inflammation, inducing a return to homeostasis in NK and T cells without compromising the anti-Spike protein antibody response. CD24Fc significantly attenuated the systemic cytokine response and diminished the cytokine coexpression and network connectivity linked with COVID-19 severity and pathogenesis. Conclusions Our data demonstrate that CD24Fc rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19.

Cardiovascular disease (CVD) is more frequent among people with HIV (PWH) and may relate to traditional and nontraditional factors, including inflammation and immune activation. A critical need exists to develop effective strategies to prevent CVD in this population.The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) (A5332) is a prospective, randomized, placebo-controlled trial of a statin strategy for the primary prevention of major adverse cardiovascular events (MACE) in PWH with low to moderate traditional risk. At least 7,500 PWH, 40-75 years of age, on stable antiretroviral therapy, will be randomized to pitavastatin calcium (4 mg/d) or identical placebo and followed for up to 8 years. Participants are enrolled based on the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) atherosclerotic cardiovascular disease (ASCVD) risk score and low-density lipoprotein cholesterol (LDL-C) level with a goal to identify a low- to moderate-risk population who might benefit from a pharmacologic CVD prevention strategy. Potential participants with a risk score ≤ 15% were eligible based on decreasing LDL-C thresholds for increasing risk score7.5% (LDL-C190 mg/dL for risk score7.5%, LDL-C160 mg/dL for risk score 7.6%-10%, and LDL-C130 mg/dL for risk score 10.1%-15%). The primary objective is to determine effects on a composite end point of MACE. Formal and independent adjudication of clinical events will occur using standardized criteria. Key secondary end points include effects on MACE components, all-cause mortality, specified non-CVD events, AIDS and non-AIDS events, and safety.To date, REPRIEVE has enrolled7,500 participants at approximately 120 sites across 11 countries, generating a diverse and representative population of PWH to investigate the primary objective of the trial.REPRIEVE is the first trial investigating a primary CVD prevention strategy in PWH. REPRIEVE will inform the field of the efficacy and safety of a statin strategy among HIV-infected participants on antiretroviral therapy and provide critical information on CVD mechanisms and non-CVD events in PWH.

Background We aimed to investigate whether there are differences in cardiac structure and systolic and diastolic function evaluated by 2‐dimensional echocardiography among men living with versus without HIV in the era of combination antiretroviral therapy. Methods and Results We performed a cross‐sectional analysis of 1195 men from MACS (Multicenter AIDS Cohort Study) who completed a transthoracic echocardiogram examination between 2017 and 2019. Associations between HIV serostatus and echocardiographic indices were assessed by multivariable regression analyses, adjusting for demographics and cardiovascular risk factors. Among men who are HIV+, associations between HIV disease severity markers and echocardiographic parameters were also investigated. Average age was 57.1±11.9 years; 29% of the participants were Black, and 55% were HIV+. Most men who were HIV+ (77%) were virally suppressed; 92% received combination antiretroviral therapy. Prevalent left ventricular (LV) systolic dysfunction (ejection fraction 3 versus Conclusions HIV seropositivity was independently associated with greater LV mass index, left atrial and RV sizes, lower RV function and diastolic abnormalities, but not left ventricular ejection fraction, which may herald a future predisposition to heart failure with preserved ejection fraction among men living with HIV.

With the development of potent and effective antiretroviral therapy (ART), life expectancy for people with HIV (PWH) has increased to the point that HIV is now considered a chronic illness. People with HIV are at increased risk of atherosclerotic cardiovascular disease (ASCVD) compared to the general population due to multiple factors, including traditional risk factors as well as immune activation and chronic inflammation due to HIV infection itself. Dyslipidemia in HIV is an important comorbidity that contributes to increased ASCVD risk in PWH. Low high-density lipoprotein (HDL) with elevated triglycerides (TG) is a common lipid pattern in PWH. Management of dyslipidemia requires close attention to important drug-drug interactions between antiretrovirals (ARV) and statins.

The use of antiretroviral therapy (ART) as preexposure prophylaxis (PrEP) is an effective strategy for preventing HIV acquisition. The cellular consequences of PrEP exposure, however, have not been sufficiently explored to determine potential effects on health in individuals without HIV. In this study, peripheral blood mononuclear cells (PBMCs) from people without HIV were exposed to tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC) overnight. Mitochondrial mass and function were measured by flow cytometry and an Agilent XFp analyzer., The use of antiretroviral therapy (ART) as preexposure prophylaxis (PrEP) is an effective strategy for preventing HIV acquisition. The cellular consequences of PrEP exposure, however, have not been sufficiently explored to determine potential effects on health in individuals without HIV. In this study, peripheral blood mononuclear cells (PBMCs) from people without HIV were exposed to tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC) overnight. Mitochondrial mass and function were measured by flow cytometry and an Agilent XFp analyzer. Monocyte-derived macrophages (MDMs) were differentiated in 20% autologous serum for 5 days in the presence or absence of TDF or FTC, and surface markers, lipid uptake, and efferocytosis were measured by flow cytometry. MDM gene expression was measured using transcriptome sequencing (RNA-seq). Plasma lipids were measured using mass spectrometry. PBMCs exposed to TDF or FTC had decreased maximal oxygen consumption rate (OCR) and reduced mitochondrial mass. Exposure to PrEP also increased reactive oxygen species (ROS) production from monocyte subsets. Compared to MDMs cultured in medium alone, cells differentiated in the presence of TDF (829 genes) or FTC (888 genes) had significant changes in gene expression. Further, PrEP-exposed MDMs had decreased mitochondrial mass and displayed increased lipid uptake and reduced efferocytosis. Plasma biomarkers and lipid levels were also altered in vivo in individuals receiving a PrEP regimen. In conclusion, exposure of leukocytes to TDF or FTC resulted in decreased mitochondrial function and altered functional and transcriptional profiles. These findings may have important implications for the metabolic and immunologic consequences of PrEP in populations at risk for HIV acquisition.

Background Patterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described. Methods The REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40–75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics. Results A total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45–55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447–826/ µ L), and the median duration of prior ART use, 9.5 years (5.3–14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status. Conclusions There were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV. Clinical Trials Registration NCT02344290.

PURPOSE OF REVIEW: This article reviews recent epidemiologic trends in HIV and HCV and strategies for treatment and prevention of these infections as they relate to the opioid epidemic. RECENT FINDINGS: Among people who inject drugs (PWID) in the United States (US), HIV diagnoses are decreasing while HCV is increasing. Care for HIV and HCV relies heavily on specialist infrastructure, which is lacking in rural areas. Antiretrovirals for HIV and direct-acting antivirals for HCV are effective among PWID, yet multiple barriers make it difficult for rural injectors to access these treatments. Similarly, access to syringe service programs, medication assisted therapy for opioid addiction, and pre-exposure prophylaxis for HIV are all limited in rural areas. SUMMARY: Previous research on HIV and HCV among PWID has focused on urban or international populations, yet the US opioid epidemic is moving away from metropolitan centers. Increasing rurality of opioid injection brings unique challenges in treatment and prevention. Research into the care of HIV, HCV and opioid use disorder among rural populations is urgently needed.

Background Monoclonal antibody therapy (MAT) was granted Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration for treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adults with positive SARS-CoV-2 viral testing and at high risk for progression to severe COVID-19 with up to 10 days of symptoms. This study assessed the impact of MAT on COVID-19-related ER visits, admissions, and mortality for patients diagnosed with COVID-19. Methods This was a single-center, retrospective study at The Ohio State University Wexner Medical Center to compare COVID-19-related ER visits, admissions, and mortality at 30 days after receiving MAT in the outpatient setting with either bamlanivimab or casirivimab-imdevimab in adult patients diagnosed with SARS-CoV-2 between November 16, 2020 and February 2, 2021. Outcomes in patients who received MAT were compared to those of a control group of patients diagnosed with COVID-19 in the outpatient setting from May 16, 2020 through November 15, 2020 who would have qualified for MAT through EUA criteria had it been available. Statistical analysis used logistic regression analysis with backward selection to determine the odds ratios (OR) and the 95% confidence interval to evaluate the relationship between patient clinical characteristics and outcomes. Results This study cohort included 1,944 patients, including 943 who received MAT and 1,001 in the control group. The MAT group included 658 who received bamlanivimab and 285 who received casirivimab-imdevimab. Patients who received MAT compared to the control group had a lower rate of COVID-19 related ER visits (3.3% vs 7.4%, p = < 0.0001) and hospital admissions (4.0% vs 7.8%, p = < 0.0001). No statistically significant difference was seen in mortality between the MAT group (0.5%) and control group (1.1%, p = 0.17). After accounting for potential confounders, the difference between the monoclonal antibody and control groups remained significant for ER visits and hospital admissions as reflected in the table. Conclusion Patients who received MAT for COVID-19 in the outpatient setting had a lower rate of COVID-19-related 30 day ER visits and hospitalizations compared to those who did not receive MAT, adjusting for potential confounders. Disclosures Mohammad Mahdee Sobhanie, M.D., Regeneron (Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator, Was a sub-investigator for Regeneron 2066 and 2069) Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)

Background Limited options currently exist for treatment of patients diagnosed with symptomatic coronavirus 2019 (COVID-19). Monoclonal antibody therapy (MAT) has been investigated as a therapeutic option for symptomatic COVID-19 patients in the outpatient setting at high-risk for progression to severe disease based on emergency use authorization (EUA) criteria. No published studies have compared outcomes for patients treated with different MAT for COVID-19. Methods This was a single-center, retrospective cohort study at The Ohio State University Wexner Medical Center to compare COVID-19-related emergency room (ER) visits, admissions, and mortality at 30 days after MAT infusion for adult patients with symptomatic SARS-CoV-2 between November 16, 2020 and February 2, 2021 who received bamlanivimab versus those who received casirivimab-imdevimab. Statistical analysis used logistic regression analysis to determine the odds ratio (OR) to evaluate the relationship between patient characteristics, MAT, and outcomes. Results The cohort included 943 patients with SARS-CoV-2 who received MAT, including 658 patients who received bamlanivimab and 285 who received casirivimab-imdevimab. Outcome results between patients who received bamlanivimab and casirivimab-imdevimab showed no statistically significant difference seen in the number of COVID-19 related ER visits (3.2% vs 3.5%, p = 0.80), hospital admissions (4.6% vs 2.8%, p = 0.21), or mortality (0.5% vs 0.7%, p = 0.63). Multivariate analysis showed no statistically significant difference in outcomes between the groups when accounting for potential confounders. As reflected in the Table, chronic lymphocytic leukemia (CLL), gender, and asthma were associated with increased COVID-19 related ER visit within 30 days of infusion and age, chronic obstructive pulmonary disease, CLL, and lupus were associated with increased risk for COVID-19 related admission within 30 days of infusion. Age and obesity with body mass index greater than 35 mg/kg2 were associated with increased risk for COVID-19 related mortality at 30 days. Conclusion COVID-19 related outcomes were similar when comparing patients with COVID-19 treated with bamlanivimab versus those treated with casirivimab-imdevimab. Disclosures Mohammad Mahdee Sobhanie, M.D., Regeneron (Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator, Was a sub-investigator for Regeneron 2066 and 2069) Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)

Background ART-associated weight gain, metabolic disorders, and co-morbidities such as cardiovascular disease are challenges in long-term human immunodeficiency virus (HIV) care. We explore the effects of different ART classes on lipids at The Ohio State University Medical Center Infectious Diseases Clinic. Methods This was a retrospective, cohort study of adult PWH on ART for ≥ 3 months seen at our clinic from 1/1/2015 to 1/1/2017. Patients with CD4+ count < 200 cells/mm3 and viral load >200 copies/mL, history of malignancy, or pregnancy were excluded. Lipid values were collected over the study period. The primary outcome was change in total cholesterol (TC), high density lipoprotein (HDL) cholesterol, and non-HDL cholesterol over the study period. Multivariable regression was used to model these outcomes. Results Among 411 PWH who met criteria, 87.4% were male, and 43.3% had a baseline diagnosis of hyperlipidemia. 21.1% were on a protease inhibitor (PI), 45% were on a non-nucleoside reverse transcriptase inhibitor (NNRTI), and 37% were on an integrase strand transfer inhibitor (INSTI). 70.1% were on tenofovir disoproxil fumarate (TDF)/ emtricitabine (FTC), 20.7% were on abacavir (ABC)/ lamivudine (3TC), and 4.4% were on TAF/FTC. The mean population (MP) difference in TC was -1.54 ± 1.34 mg/dL (p=0.25), the MP difference in non-HDL cholesterol was -1.78 ± 1.26 mg/dL (p=0.16), and the MP difference in HDL cholesterol was 0.24 ± 0.43 mg/dL (p=0.6). In multivariable linear regression models (Table 1), TAF/FTC was associated with a change of TC of 18.2 ± 6.4 mg/dL (P= 0.005), a change of non-HDL cholesterol of 12.0 ± 6.0 mg/dL (p=0.046), and a change of HDL cholesterol of 6.2 ± 2.1 mg/dL (p=0.003). These models included terms for months of follow up, male gender and baseline hyperlipidemia. Though race, diabetes mellitus, and ethnicity were not significant in the model, after adjustments for them, PWH on TAF/FTC showed a change of TC of 18.0 ± 6.4 mg/dL (p=0.005), a change of non-HDL cholesterol of 11.8 ± 6.0 mg/dL (P=0.051), and a change of HDL of 6.2 ± 2.1 (p=0.03). Multivariable Linear Regression Models for Change in Total Cholesterol and Non-HDL Cholesterol Conclusion Prior studies have shown an increase in lipid levels associated with TAF compared to TDF. This study shows that TAF is an independent risk factor for increased TC, non-HDL cholesterol, and HDL cholesterol in the PWH population as a whole. Disclosures Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)

Key Points Question What is the extent of coronary artery disease among people with well-controlled HIV and low to moderate risk of atherosclerotic cardiovascular disease (ASCVD), and how is coronary artery disease associated with traditional risk, inflammatory, and immune activation indices? Findings In this cohort study of 755 people with HIV, coronary plaque was highly prevalent. Critical stenosis was rare, but higher-risk plaque features, including vulnerable plaque and high Leaman scores, were seen in approximately one-fifth of participants; plaque indices were associated with ASCVD risk scores and, independently, indices of inflammation and immune activation. Meaning These findings suggest that people with HIV at low to moderate risk of cardiovascular disease have a significant prevalence of coronary plaque associated with inflammation and immune activation markers., This cohort study examines the prevalence of coronary artery disease (CAD) among adults with well-controlled HIV and low to moderate risk of atherosclerotic cardiovascular disease using computed tomography angiography and assessment of inflammation and immune activation biomarkers., Importance Cardiovascular disease (CVD) is increased among people with HIV (PWH), but little is known regarding the prevalence and extent of coronary artery disease (CAD) and associated biological factors in PWH with low to moderate traditional CVD risk. Objectives To determine unique factors associated with CVD in PWH and to assess CAD by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation. Design, Setting, and Participants This cohort study among male and female PWH, aged 40 to 75 years, without known CVD, receiving stable antiretroviral therapy, and with low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to the 2013 American College of Cardiology/American Heart Association pooled cohort equation, was part of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH conducted at 31 US sites. Participants were enrolled from May 2015 to February 2018. Data analysis was conducted from May to December 2020. Exposure HIV disease. Main Outcomes and Measures The primary outcome was the prevalence and composition of CAD assessed by coronary CTA and, secondarily, the association of CAD with traditional risk indices and circulating biomarkers, including insulin, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP). Results The sample included 755 participants, with a mean (SD) age of 51 (6) years, 124 (16%) female participants, 267 (35%) Black or African American participants, 182 (24%) Latinx participants, a low median (interquartile range) ASCVD risk (4.5% [2.6%-6.8%]), and well-controlled viremia. Overall, plaque was seen in 368 participants (49%), including among 52 of 175 participants (30%) with atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at least 50% was rare (25 [3%]), but vulnerable plaque and high Leaman score (ie, >5) were more frequently observed (172 of 755 [23%] and 118 of 743 [16%], respectively). Overall, 251 of 718 participants (35%) demonstrated coronary artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels were higher in those with plaque compared with those without (eg, median [IQR] IL-6 level, 1.71 [1.05-3.04] pg/mL vs 1.45 [0.96-2.60] pg/mL; P = .008). LpPLA2 and IL-6 levels were associated with plaque in adjusted modeling, independent of traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 95% CI, 1.02-1.12; P = .01). Conclusions and Relevance In this study of a large primary prevention cohort of individuals with well-controlled HIV and low to moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable plaque, was highly prevalent. Participants with plaque demonstrated higher levels of immune activation and arterial inflammation, independent of traditional ASCVD risk and HIV parameters.

Background Obesity is a global public health crisis with a growing prevalence in persons with human immunodeficiency virus (PWH) population. In this study, we aimed to investigate factors associated with weight gain in the PWH population. Methods This was a single-centered, retrospective cohort study of our clinic patient population from January 1, 2015 to January 1, 2019. Patients with human immunodeficiency virus (HIV) were identified from the electronic health record and a randomized sample of 300 patients who had at least two follow up appointments, were on antiretroviral therapy, and had viral loads less than 200 were evaluated. The primary outcome was weight change over follow up. Cox Proportional Hazards models were used, taking a weight gain > 3 kg as the outcome, and the time on therapy between visits as the time to event. Robust linear regression was used to model mean changes in weight, accounting for influential observations. All analysis were performed in STATA 16.0. Table 1 Results At baseline, 87% were male, 63% were white, and 65% were overweight/obese. 30% were on a protease inhibitor, 46% were on non-nucleoside reverse transcriptase inhibitor, and 37% were on an integrase inhibitor. 64% were on Tenofovir disoproxil (TDF), 8% were on Tenofovir alafenamide (TAF), and 19% were on Abacavir. Mean weight change over follow up was significantly increased at 1.31 kg (95% CI = 0.58 – 2.04 kg, p= 0.0004). TAF use and male gender were significantly associated with risk of weight gain > 3 kg in univariate analysis [respectively, OR = 2.53, 95% CI = 1.30 – 4.92, p = 0.006; OR = 2.60, 95% CI = 1.05 – 6.45, p = 0.04]. In multivariate analysis, TAF use was significantly associated with weight gain > 3 kg, while male gender was of borderline significance [respectively, OR = 2.29, 95% CI = 1.17 – 4.47, p = 0.01; OR = 2.40, 95% CI = 0.96 – 5.97, p=0.060]. Significant factors associated with weight change are noted in Table 1. Conclusion As PWH are living longer on effective ARV therapy, monitoring for weight gain is required as obesity contributes to morbidity and mortality from cardiovascular disease and metabolic diseases. Key factors for weight gain in our clinic population include male gender, baseline diagnosis of hypertension, use of TAF, bictegravir use, and rilpivirine use. Disclosures Carlos Malvestutto, MD, Gilead Sciences (Advisor or Review Panel member)ViiV Healthcare (Advisor or Review Panel member)

Background Sexually transmitted infections (STIs) disproportionally affect individuals living in underserved areas and Emergency Departments (ED) can play a major role in STI screening. Given the overlapping risk factors for STIs, patients screened for gonorrhea and chlamydia should also be screened for syphilis and HIV. Rates of syphilis/HIV screening in the ED are very low and barriers include lack of knowledge about the risk/prevalence, difficulty with results interpretation, and concerns about follow-up. Methods The main study objective was to improve rates of syphilis/HIV screening in a community-based ED in Columbus, OH. A team of clinical providers, case managers, and social workers was formed to address barriers to screening. Using root cause analysis and data feedback, a multistep intervention that included provider education along with expert review of syphilis/HIV results was implemented to ensure proper screening, treatment and rapid linkage to care. Syphilis/HIV screening rates in the ED were compared between two periods: 2012–2017 (pre-intervention) and November 2018–April 2019 (post-intervention). Results Between 2012 and 2017, there were 24,427 ED encounters where any STI test was ordered. There were 23,652 (97%) tests for chlamydia, 23,637 (97%) for gonorrhea, 254 (1%) for syphilis, and 466 (2%) for HIV. Twenty-four (0.1%) encounters had screening that included all four tests. Six months after starting the intervention, there were 1,590 encounters where any STI test was ordered. There were 1,444 (91%) tests for chlamydia, 1,446 (91%) for gonorrhea, 493 (31%) for syphilis and 591 (37%) for HIV. Four hundred thirty-eight (28%) of encounters had screening that included all four tests. Conclusion Collaborative and practical interventions aimed at improving syphilis/HIV testing have resulted in dramatic increases in syphilis, HIV, and comprehensive STI screening (31-, 19-, 280-fold, respectively) over a relatively short post-intervention period. Additional steps are planned with the goal to further increase screening rates and improve linkage to prevention and treatment programs. Disclosures All authors: No reported disclosures.

The evidence base for scaling-up hepatitis C virus (HCV) treatment and harm reduction services within rural communities is limited, and requires a better understanding of the socio-cultural context and operational issues for these distinct settings. Best practices from US urban centers, where most implementation research has been focused, do not necessarily translate to sparsely populated rural areas, where HCV and harm reduction services are limited and fragmented.

Since the discovery and development of antiretroviral therapy (ART), HIV has become a chronic disease with patients living longer lives and to ages where co-morbidities, such as cardiovascular disease (CVD) are prevalent. Diagnosis and management of risk factors for CVD, in particular dyslipidemia, have become an important part of the overall care for patients living with HIV infection. Existing guidelines and recommendations for the management of dyslipidemia for persons with HIV infection are largely based on guidelines for the general population. Clinical and epidemiologic research efforts are ongoing to provide information specific to patients living with HIV. This review offers a detailed guide for clinicians who manage dyslipidemia in patients infected with HIV. The first sections provide background information on dyslipidemia, risk stratification, and targets for lipid therapy. This is followed by a step-by-step approach for diagnosis and treatment with specific information on lipid drug use for patients with HIV. The recommendations presented here are based on existing guidelines for the general population, evidence from research in patients infected with HIV, and the clinical experience of the authors. Management issues for which little or no information is available specific to this patient population are noted and serve to highlight the many gaps in our knowledge that will need to be addressed.