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Abstract Background We aimed to determine the reliability and validity of a hepatitis symptom inventory and to identify predictors of hepatitis C (HCV) treatment initiation in a cohort of HIV-infected patients. Methods Prospective clinic based study that enrolled patients referred for HCV therapy consideration. A hepatitis symptom inventory and the Center for Epidemiologic Studies Depression Scale (CES-D) were administered to HIV/HCV individuals. The symptom inventory was factor analyzed and subscale reliability estimated with Cronbach's alpha. Predictive validity was evaluated using generalized estimating equations (GEE). Predictors of HCV treatment were identified using logistic regression. Results Between April 2008 to July 2010, 126 HIV/HCV co-infected patients were enrolled in the study. Factor analysis using data from 126 patients yielded a three-factor structure explaining 60% of the variance for the inventory. Factor 1 (neuropsychiatric symptoms) had 14 items, factor 2 (somatic symptoms) had eleven items, and factor 3 (sleep symptoms) had two items, explaining 28%, 22% and 11% of the variance, respectively. The three factor subscales demonstrated high intrinsic consistency reliability. GEE modeling of the 32 patients who initiated HCV therapy showed that patients developed worsening neuropsychiatric and somatic symptoms following HCV therapy with stable sleep symptoms. Bivariate analyses identified the following as predictors of HCV therapy initiation: lower HIV log10 RNA, lower scores for neuropsychiatric, somatic and sleep symptoms, lower CES-D scores and white ethnicity. In stepwise multiple logistic regression analysis, low neuropsychiatric symptom score was the strongest independent predictor of HCV therapy initiation and HIV log10 RNA was inversely associated with a decision to initiate HCV treatment. Conclusions A 41-item hepatitis-related symptom inventory was found to have a clinically meaningful 3-factor structure with excellent internal consistency reliability and predictive validity. In adjusted analysis, low neuropsychiatric symptom scores and controlled HIV infection were independent predictors of HCV treatment initiation. The usefulness of the HCV symptom inventory in monitoring HCV treatment should be evaluated prospectively.

Abstract Background This study aimed to evaluate the prevalence and predictors of AIDS-related complicated cryptococcal meningitis. The outcome was complicated cryptococcal meningitis: prolonged (≥ 14 days) altered mental status, persistent (≥ 14 days) focal neurologic findings, cerebrospinal fluid (CSF) shunt placement or death. Predictor variable operating characteristics were estimated using receiver operating characteristic curve (ROC) analysis. Multivariate analysis identified independent predictors of the outcome. Results From 1990-2009, 82 patients with first episode of cryptococcal meningitis were identified. Of these, 14 (17%) met criteria for complicated forms of cryptococcal meningitis (prolonged altered mental status 6, persistent focal neurologic findings 7, CSF surgical shunt placement 8, and death 5). Patients with complicated cryptococcal meningitis had higher frequency of baseline focal neurological findings, head computed tomography (CT) abnormalities, mean CSF opening pressure, and cryptococcal antigen (CRAG) titers in serum and CSF. ROC area of log2 serum and CSF CRAG titers to predict complicated forms of cryptococcal meningitis were comparable, 0.78 (95%CI: 0.66 to 0.90) vs. 0.78 (95% CI: 0.67 to 0.89), respectively (χ2, p = 0.95). The ROC areas to predict the outcomes were similar for CSF pressure and CSF CRAG titers. In a multiple logistic regression model, the following were significant predictors of the outcome: baseline focal neurologic findings, head CT abnormalities and log2 CSF CRAG titer. Conclusions During initial clinical evaluation, a focal neurologic exam, abnormal head CT and large cryptococcal burden measured by CRAG titer are associated with the outcome of complicated cryptococcal meningitis following 2 weeks from antifungal therapy initiation.

Abstract: Smoking is a myocardial infarction (MI) risk factor among people with HIV (PWH). Questions persist regarding the role of smoking behaviors and measurements (e.g., intensity, duration) on MI risk. We used Cox proportional hazards regression to compare the association of smoking parameterization with incidents of type 1 and type 2 MI and whether smoking intensity or duration improves MI risk prediction among PWH. Among 11,637 PWH, 37% reported currently smoking, and there were 346 MIs. Current smoking was associated with type 1 (84% increased risk) but not type 2 MI in adjusted analyses. The type 1 MI model with pack years had the best goodness of fit compared with other smoking parameterizations. Ever or never parameterization and smoking diagnosis data had significantly poorer model fit. These results highlight the importance of differentiating MI types and performing patient-based smoking assessments to improve HIV care and research rather than relying on smoking status from diagnoses., (Copyright © 2024 Association of Nurses in AIDS Care.)

Background: Frailty occurs at higher rates and younger ages among people with HIV (PWH) compared to the general population and is often attributed to chronic inflammation and subsequent immune exhaustion. We assessed how inflammatory biomarkers are associated with frailty among PWH., Methods: The Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort is comprised of adult PWH in care at 10 sites, and harmonizes demographic, clinical, and patient-reported outcomes (PRO) data. A panel of 13 inflammatory biomarkers was collected from a subset of virally suppressed PWH once per person between 2010-2018. Frailty was measured with a validated PRO phenotype, scored 0-4, from biomarker collection date through July 2022. With adjusted linear mixed models, we estimated longitudinal associations between standard deviation-scaled log2-transformed biomarkers and frailty score., Results: Among 273 PWH, most were male (91%), average age at baseline was 45, 42% were non-Hispanic White while 35% were non-Hispanic Black, and average follow-up time was 5.5 years. Several biomarkers were associated with higher frailty, including those linked to microbial translocation (sCD14, LBP, KT ratio) and systemic inflammation (CRP, IL-6, suPAR, sTNFR1, sTNFR2). Higher IL-6 was associated with a 0.25-point higher frailty score (95%CI:0.12-0.39). Higher sTNFR1 (0.35 [0.13-0.56]), sCD14 (0.21 [0.11-0.31]), and suPAR (0.24 [0.11-0.36]) levels were also associated with higher frailty scores over follow-up., Conclusions: Higher levels of biomarkers linked to microbial translocation and systemic inflammation are associated with higher average frailty scores over time in a cohort of virally suppressed PWH, highlighting these pathways as potential interventional targets for mitigating frailty in PWH., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Although stroke risk associated with HIV may be greater for women than men, little is known about whether the impact of different factors on cerebrovascular risk varies by sex in people with HIV (PWH) and contributes to stroke risk disparities in this population. The primary objective of this study was to examine whether sex modifies the effect of demographics, cardiometabolic factors, health-related behaviors, and HIV-specific variables on stroke risk in PWH from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort., Methods: In this observational cohort study, we analyzed data from clinical encounters for PWH followed at 5 CNICS sites from approximately 2005 to 2020. All potential stroke events were adjudicated by neurologists. Patient-reported outcomes collected at clinic visits, including substance use and depression, were also available. We used Cox proportional hazards models to determine whether sex modified the association of predictors of interest with incident stroke., Results: Among 13,573 PWH (19% female sex at birth, mean age 44 years, mean follow-up 5.6 years), female sex was associated with a higher risk of stroke only among individuals aged 50 years or younger (hazard ratio [HR] 2.01 at age 40 [1.25-3.21] vs HR 0.60 at age 60 [0.34-1.06]; p = 0.001 for the interaction). Younger female participants who developed a stroke were more likely to have treated hypertension, a higher cardiovascular risk score, and detectable HIV than younger male participants whereas these factors were comparable by sex among older participants who developed a stroke. Sex modified the effect of detectable HIV (HR 4.66 for female participants [2.48-8.74] vs HR 1.30 for male participants [0.83-2.03]; p = 0.001 for the interaction), methamphetamine use (HR 4.78 for female participants [1.47-15.56] vs HR 1.19 for male participants [0.62-2.29]; p = 0.04 for the interaction), and treated hypertension (HR 3.44 for female participants [1.74-6.81] vs HR 1.66 for male participants [1.14-2.41]; p = 0.06 for the interaction) on stroke risk., Discussion: Younger female participants with HIV were at elevated cerebrovascular risk compared with younger male participants. Several risk factors had a greater adverse effect on stroke risk in female participants than in male participants, including HIV viremia, methamphetamine use, and treated hypertension. These findings underscore the importance of a personalized approach to predict and prevent cerebrovascular risk among PWH.

Background: Few studies have examined which subgroups of people with HIV (PWH) carry the greatest burden of internalized HIV stigma (IHS), which may be important to care provision and interventions., Methods: PWH in the CFAR Network of Integrated Clinical Systems (CNICS) longitudinal, US-based, multisite, clinical care cohort completed tablet-based assessments during clinic visits including a four-item, Likert scale (low 1-5 high), IHS instrument. Associations between sociodemographic characteristics and IHS scores were assessed in adjusted linear regression models., Results: Twelve thousand six hundred and fifty-six PWH completed the IHS assessment at least once from February 2016 to November 2022, providing 28 559 IHS assessments. At baseline IHS assessment, the mean age was 49 years, 41% reported White, 38% Black/African American, and 16% Latine race/ethnicity, and 80% were cisgender men. The mean IHS score was 2.04, with all subgroups represented among those endorsing IHS. In regression analyses, younger PWH and those in care fewer years had higher IHS scores. In addition, cisgender women vs. cisgender men, PWH residing in the West vs. the Southeast, and those with sexual identities other than gay/lesbian had higher IHS scores. Compared with White-identifying PWH, those who identified with Black/African American or Latine race/ethnicity had lower IHS scores. Age stratification revealed patterns related to age category, including specific age-related differences by gender, geographic region and race/ethnicity., Discussion: IHS is prevalent among PWH, with differential burden by subgroups of PWH. These findings highlight the benefits of routine screening for IHS and suggest the need for targeting/tailoring interventions to reduce IHS among PWH., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Among 8455 people engaged in HIV care in 4 US cities, 4925 (58%) had treponemal testing at care entry. Of the 4925 tested, 3795 (77%) had a nonreactive result and might benefit from the reverse algorithm for a future incident syphilis diagnosis. Furthermore, low-barrier treponemal testing as a first step in the reverse algorithm may increase syphilis screening and decrease time to treatment., Competing Interests: Conflict of Interest and Sources of Funding: The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript. The Center for AIDS Research Network of Integrated Clinical Systems is funded by NIH NIAID R24 AI067039., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: This study examined the relationships among adiposity, handgrip, physical function, inflammation (ie, senescence-associated secretory phenotype chemokines as biomarkers of aging and frailty), and sex hormones in aging people with HIV., Methods: This cross-sectional exploratory study included 150 people with HIV aged ≥40 years (67.3% of participants were male). Our measures included (1) body mass index and waist circumference as measures of adiposity; (2) handgrip as a measure of muscle strength; (3) short physical performance battery as a measure of physical function; (4) interleukin-6, tumor necrosis factor alpha receptor II, high sensitivity C-reactive protein, C-X-C motif chemokine 10, and C-X3-C motif chemokine ligand 1 also known as fractalkine as senescence-associated secretory phenotype chemokines; and (5) free testosterone, estradiol, sex hormone-binding globulin, and dehydroepiandrosterone as sex hormones. Quantile regression analyses were used to identify relationships among inflammatory markers and hormones with age, adiposity, handgrip, and physical function., Results: Overall, 74% (n = 111) of participants were classified as overweight or obese and 53.3% (n = 80) presented with abdominal obesity. After controlling for age and sex, body mass index was positively associated with estradiol (β = 0.043, P < 0.01), and waist circumference was positively associated with high sensitivity C-reactive protein (β = 2.151, P < 0.01). After controlling for sex, age was positively associated with C-X-C motif chemokine 10 (β = 0.024, P = 0.03) and tumor necrosis factor alpha receptor II (β = 2.205, P = 0.01). After controlling for age and sex, short physical performance battery was negatively associated with dehydroepiandrosterone (β = -0.004, P = 0.01); no statistically significant associations were observed for handgrip., Conclusion: Adiposity levels and aging were associated with inflammation (ie, C-X-C motif chemokine 10, tumor necrosis factor alpha receptor II, and high sensitivity C-reactive protein) among people with HIV aged 40 years and older., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: There is limited real-world evidence about the effectiveness of semaglutide for weight loss among people with HIV (PWH). We aimed to investigate weight change in a US cohort of PWH who initiated semaglutide treatment., Design: Observational study using the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort., Methods: We identified adult PWH who initiated semaglutide between 2018 and 2022 and with at least two weight measurements. The primary outcome was within-person bodyweight change in kilograms at 1 year. The secondary outcome was within-person Hemoglobin A1c percentage (HbA1c) change. Both outcomes were estimated using multivariable linear mixed model., Results: In total, 222 new users of semaglutide met inclusion criteria. Mean follow-up was 1.1 years. Approximately 75% of new semaglutide users were men, and at baseline, mean age was 53 years [standard deviation (SD): 10], average weight was 108 kg (SD: 23), mean BMI was 35.5 kg/m 2 , mean HbA1c was 7.7% and 77% had clinically recognized diabetes. At baseline, 97% were on ART and 89% were virally suppressed (viral load < 50 copies/ml). In the adjusted mixed model analysis, treatment with semaglutide was associated with an average weight loss of 6.47 kg at 1 year (95% CI -7.67 to -5.18) and with a reduction in HbA1c of 1.07% at 1 year (95% CI -1.64 to -0.50) among the 157 PWH with a postindex HbA1c value., Conclusion: Semaglutide was associated with significant weight loss and HbA1c reduction among PWH, comparable to results of previous studies from the general population., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: People with HIV (PWH) are at increased risk for venous thromboembolism (VTE). We conducted this study to characterize VTE including provoking factors among PWH in the current treatment era., Methods: We included PWH with VTE between 2010 and 2020 at 6 sites in the CFAR Network of Integrated Clinical Systems cohort. We ascertained for possible VTE using diagnosis, VTE-related imaging, and VTE-related procedure codes, followed by centralized adjudication of primary data by expert physician reviewers. We evaluated sensitivity and positive predictive value of VTE ascertainment approaches. VTEs were classified by type and anatomic location. Reviewers identified provoking factors such as hospitalizations, infections, and other potential predisposing factors such as smoking., Results: We identified 557 PWH with adjudicated VTE: 239 (43%) had pulmonary embolism with or without deep venous thrombosis, and 318 (57%) had deep venous thrombosis alone. Ascertainment with clinical diagnoses alone missed 6% of VTEs identified with multiple ascertainment approaches. DVTs not associated with intravenous lines were most often in the proximal lower extremities. Among PWH with VTE, common provoking factors included recent hospitalization (n = 134, 42%), infection (n = 133, 42%), and immobilization/bed rest (n = 78, 25%). Only 57 (10%) PWH had no provoking factor identified. Smoking (46%), HIV viremia (27%), and injection drug use (22%) were also common., Conclusions: We conducted a robust adjudication process that demonstrated the benefits of multiple ascertainment approaches followed by adjudication. Provoked VTEs were more common than unprovoked events. Nontraditional and modifiable potential predisposing factors such as viremia and smoking were common., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: "Sick quitting," a phenomenon describing reductions in alcohol consumption following poor health, may explain observations that alcohol appears protective for frailty risk. We examined associations between frailty and reductions in drinking frequency among people with HIV (PWH). At six Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites between January 2012 and August 2021, we assessed whether frailty, measured through validated modified frailty phenotype, precedes reductions in drinking frequency. We associated time-updated frailty with quitting and reducing frequency of any drinking and heavy episodic drinking (HED), adjusted for demographic and clinical characteristics in Cox models. Among 5,654 PWH reporting drinking, 60% reported >monthly drinking and 18% reported ≥monthly HED. Over an average of 5.4 years, frail PWH had greater probabilities of quitting (HR: 1.56, 95% confidence interval [95% CI] [1.13-2.15]) and reducing (HR: 1.35, 95% CI [1.13-1.62]) drinking frequency, as well as reducing HED frequency (HR: 1.58, 95% CI [1.20-2.09]) versus robust PWH. Sick quitting likely confounds the association between alcohol use and frailty risk, requiring investigation for control., (Copyright © 2024 Association of Nurses in AIDS Care.)

Background: Tobacco smoking increases frailty risk among the general population and is common among people with HIV (PWH) who experience higher rates of frailty at younger ages than the general population., Methods: We identified 8608 PWH across 6 Centers for AIDS Research Network of Integrated Clinical Systems sites who completed ≥2 patient-reported outcome assessments, including a frailty phenotype measuring unintentional weight loss, poor mobility, fatigue, and inactivity, and scored 0-4. Smoking was measured as baseline pack-years and time-updated never, former, or current use with cigarettes/day. We used Cox models to associate smoking with risk of incident frailty (score ≥3) and deterioration (frailty score increase by ≥2 points), adjusted for demographics, antiretroviral medication, and time-updated CD4 count., Results: The mean follow-up of PWH was 5.3 years (median: 5.0), the mean age at baseline was 45 years, 15% were female, and 52% were non-White. At baseline, 60% reported current or former smoking. Current (HR: 1.79; 95% confidence interval: 1.54 to 2.08) and former (HR: 1.31; 95% confidence interval: 1.12 to 1.53) smoking were associated with higher incident frailty risk, as were higher pack-years. Current smoking (among younger PWH) and pack-years, but not former smoking, were associated with higher risk of deterioration., Conclusions: Among PWH, smoking status and duration are associated with incident and worsening frailty., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: People with human immunodeficiency virus (HIV) infection (PWH) are at higher risk of myocardial infarction (MI) than those without HIV. About half of MIs in PWH are type 2 (T2MI), resulting from mismatch between myocardial oxygen supply and demand, in contrast to type 1 MI (T1MI), which is due to primary plaque rupture or coronary thrombosis. Despite worse survival and rising incidence in the general population, evidence-based treatment recommendations for T2MI are lacking. We used polygenic risk scores (PRS) to explore genetic mechanisms of T2MI compared to T1MI in PWH., Methods: We derived 115 PRS for MI-related traits in 9541 PWH enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort with adjudicated T1MI and T2MI. We applied multivariate logistic regression analyses to determine the association with T1MI and T2MI. Based on initial findings, we performed gene set enrichment analysis of the top variants composing PRS associated with T2MI., Results: We found that T1MI was strongly associated with PRS for cardiovascular disease, lipid profiles, and metabolic traits. In contrast, PRS for alcohol dependence and cholecystitis, significantly enriched in energy metabolism pathways, were predictive of T2MI risk. The association remained after the adjustment for actual alcohol consumption., Conclusions: We demonstrate distinct genetic traits associated with T1MI and T2MI among PWH further highlighting their etiological differences and supporting the role of energy regulation in T2MI pathogenesis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Alcohol use among people with HIV is associated with worse HIV treatment outcomes. Its impact on self-reported health status is unclear., Setting: Longitudinal cohort of people with HIV engaged in care across 7 clinics participating in the Centers for AIDS Research Network of Integrated Care Systems between January 2011 and June 2014., Methods: A total of 5046 participants were studied. A quantile regression model estimated the association of alcohol use levels with subsequent self-reported health status score, accounting for multiple covariates including depressive symptoms. Women, men who have sex with women, and men who have sex with men were analyzed separately., Results: Prevalence of heavy alcohol use was 21%, 31%, and 37% among women, men who have sex with women, and men who have sex with men, respectively. Women with heavy alcohol use had a subsequently decreased median self-reported health status score compared to women with no or moderate alcohol use (odds ratio [OR]: 0.76; 95% confidence interval [CI]: 0.58-0.99); this association was not explained by the presence of depressive symptoms. There was no observed association of alcohol use level on subsequent self-reported health status among men who have sex with women. Men who have sex with men reporting no alcohol use had a subsequently decreased median self-reported health status compared to moderate alcohol use (OR: 0.88; 95% CI: 0.80-0.97)., Conclusion: Heavy alcohol use is associated with worsened self-reported health status at subsequent visits among women with HIV and not men with HIV., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objectives: People with HIV have a higher risk of myocardial infarction (MI) than the general population, with a greater proportion of type 2 MI (T2MI) due to oxygen demand-supply mismatch compared with type 1 (T1MI) resulting from atherothrombotic plaque disruption. People living with HIV report a greater prevalence of cigarette and alcohol use than do the general population. Alcohol use and smoking as risk factors for MI by type are not well studied among people living with HIV. We examined longitudinal associations between smoking and alcohol use patterns and MI by type among people living with HIV., Design and Methods: Using longitudinal data from the Centers for AIDS Research Network of Integrated Clinical Systems cohort, we conducted time-updated Cox proportional hazards models to determine the impact of smoking and alcohol consumption on adjudicated T1MI and T2MI., Results: Among 13 506 people living with HIV, with a median 4 years of follow-up, we observed 177 T1MI and 141 T2MI. Current smoking was associated with a 60% increase in risk of both T1MI and T2MI. In addition, every cigarette smoked per day was associated with a 4% increase in risk of T1MI, with a suggestive, but not significant, 2% increase for T2MI. Cigarette use had a greater impact on T1MI for men than for women and on T2MI for women than for men. Increasing alcohol use was associated with a lower risk of T1MI but not T2MI. Frequency of heavy episodic alcohol use was not associated with MI., Conclusions: Our findings reinforce the prioritization of smoking reduction, even without cessation, and cessation among people living with HIV for MI prevention and highlight the different impacts on MI type by gender., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients., Methods: We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm., Results: Among 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving control plasma were still symptomatic (P = .78) at day 14. Associations between CCP and symptom resolution by day 14 did not differ significantly from those in controls after adjustment for baseline characteristics (adjusted subdistribution hazard ratio, 0.99; P = .62). The most common cluster consisted of cough, fatigue, shortness of breath, and headache and was found in 308 (57.2%) and 325 (61.1%) of CCP and control plasma recipients, respectively (P = .16)., Conclusions: In this trial of outpatients with early COVID-19, CCP was not associated with faster resolution of symptoms compared with control. Overall, there were no differences by treatment in the prevalence of each symptom or symptom clusters at day 14., Clinical Trials Registration: NCT04373460., Competing Interests: Potential conflicts of interest. E. M. B. is a member of the Food and Drug Administration's Blood Products Advisory Committee. (All opinions in this manuscript are of the authors and do not reflect the Blood Products Advisory Committee or the position of the Food and Drug Administration; this arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies.) A. C. serves on the Scientific Advisory Board of Sabtherapeutics, which is developing cow-derived human immunoglobulins for the treatment of coronavirus disease 2019 and other infectious diseases. K. A. G. is a paid consultant for UpToDate, Teach for America, and the Aspen Institute. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Frailty is common among people with HIV (PWH), so we developed frail risk in the short-term for care (RISC)-HIV, a frailty prediction risk score for HIV clinical decision-making., Design: We followed PWH for up to 2 years to identify short-term predictors of becoming frail., Methods: We predicted frailty risk among PWH at seven HIV clinics across the United States. A modified self-reported Fried Phenotype captured frailty, including fatigue, weight loss, inactivity, and poor mobility. PWH without frailty were separated into training and validation sets and followed until becoming frail or 2 years. Bayesian Model Averaging (BMA) and five-fold-cross-validation Lasso regression selected predictors of frailty. Predictors were selected by BMA if they had a greater than 45% probability of being in the best model and by Lasso if they minimized mean squared error. We included age, sex, and variables selected by both BMA and Lasso in Frail RISC-HIV by associating incident frailty with each selected variable in Cox models. Frail RISC-HIV performance was assessed in the validation set by Harrell's C and lift plots., Results: Among 3170 PWH (training set), 7% developed frailty, whereas among 1510 PWH (validation set), 12% developed frailty. BMA and Lasso selected baseline frailty score, prescribed antidepressants, prescribed antiretroviral therapy, depressive symptomology, and current marijuana and illicit opioid use. Discrimination was acceptable in the validation set, with Harrell's C of 0.76 (95% confidence interval: 0.73-0.79) and sensitivity of 80% and specificity of 61% at a 5% frailty risk cutoff., Conclusions: Frail RISC-HIV is a simple, easily implemented tool to assist in classifying PWH at risk for frailty in clinics., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Vaporized nicotine (VN) use is increasing among people with HIV (PWH). We examined demographics, patterns of use, depression, and panic symptoms associated with VN and combustible cigarette (CC) use among PWH., Methods: We analyzed VN use among PWH in care at 7 US sites. PWH completed a set of patient-reported outcomes, including substance use and mental health. We categorized VN use as never vs. ever with the frequency of use (days/month) and CC use as never, former, or current. We used relative risk regression to associate VN and CC use, depression, and panic symptoms. Linear regression estimated each relationship with VN frequency. Models were adjusted for demographics., Results: Among 7431 PWH, 812 (11%) reported ever-using VN, and 264 (4%) reported daily use. Half (51%) of VN users concurrently used CC. VN users were more likely than those without use to be younger, to be White, and to report ever-using CC. PWH reporting former CC use reported ≥8.5 more days per month of VN use compared with never CC use [95% confidence interval (95% CI): 5.5 to 11.5 days/month] or current CC use (95% CI: 6.6 to 10.5 days/month). Depression (relative risk: 1.20 [95% CI: 1.02 to 1.42]) and panic disorder (1.71 [95% CI: 1.43 to 2.05]) were more common among PWH ever-using VN. Depression was common among PWH using VN (27%) and CC (22%), as was panic disorder (21% for VN and 16% for CC)., Conclusion: Our study elucidated demographic associations with VN use among PWH, revealed the overlap of VN and CC use, and associations with depression/panic symptoms, suggesting roles of VN in self-medication and CC substitution, warranting further longitudinal/qualitative research., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection., Methods: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection., Results: In total, 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) positivity. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs 25.2 days; P = .49) and COVID-19 (26.3 vs 25.9 days; P = .35) was similar for both groups., Conclusions: Administration of high-titer CCP as post-exposure prophylaxis, although appearing safe, did not prevent SARS-CoV-2 infection., Clinical Trials Registration: NCT04323800., Competing Interests: Potential conflicts of interests . The authors report the following: K. G.reports grants or contracts unrelated to this work and paid to institution from NIHI, personal fees from Aspen Institute, Teach for America and UpToDate. T. G. reports paid consultant for Fresenius Kabi USA and reports <$5000 of JNJ stock. A. C. reports Scientific Advisory Board of Sabtherapeutics (cow-derived human immunoglobulins COVID-19 treatment and other infectious diseases) and Ortho Diagnostics Speakers Bureau, and consulting fees from Ortho Diagnostics and Pfizer, and payment for expert testimony from King & Spalding LLP, and leadership or fiduciary role with American Society for Microbiology, and part owner of Melatech. E. B.’s time is funded in part by National Heart Lung and Blood Institute (NHLBI) through grant number 1K23HL151826, is a member of the FDA Blood Products Advisory Committee, Abbot Laboratories, Grifols Diagnostic Solutions, personal fee for invited educational presentations for Terumo BCT (honoraria for educational webinar), and advisor for California Institute for Regenerative Medicine (convalescent plasma program), and unpaid participation as invited member for a Data Safety Monitoring Board for the following trial: ‘Assessment of safety and efficacy of COVID-19 Convalescent Plasma for treatment of COVID-19 in adults in Uganda; A Phase III randomized controlled trial. S. S. reports research grants from Ansun, Astellas, Cidara, Emergent Biosolutions, F2G, Gilead, Merck, Scynexis, Zeteo, Shionogi and Shire, personal fees from Adagio, Adamis, Celltrion, Immunome, Intermountain Health and Karyopharm (consultant, advisory board and data safety monitoring board member), participation on a Data Safety Monitoring Board or Advisory Board for Adagio, Adamis, Amplyx, Immunome, Intermountain Health, Janssen, Karyopharm, Reviral, and stock options from Immunome. D. Su. reports grants or contracts unrelated to this work from NIH/NIAID (R01AI150763 Dual artemisinin action combats resistance; NIH R21TR001737 Quantum model repurposing of cethromycin for liver stage malaria; NIH R01AI111962 Optimized Combination Antimalarial Drug Therapy), founder, board member, and stock options from AliquantumRx, DSMB member NIAID SMC/ISM Intramural 2018, medical royalties for malaria test (Binax Inc/D/B/A Inverness), consultant on malaria diagnosis for Masimo and Hemex Health and consulting fees for legal malaria case (Mabrey Firm 2019 and Ressler and Ressler 2018), and patents (Issued-USP 9,642,865 9 May 2017 New angiogenesis inhibitors; Issued-USP 9,568,471 14 February 2017 Malaria Diagnosis in Urine; Issued-USP 7,270,948 18 September 2007 Detection of malaria parasites by laser desorption mass spectrometry; Pending SALTS AND POLYMORPHS OF CETHROMYCIN FOR THE TREATMENT OF DISEASE Patent Application (Application number 20210163522); and Pending- Macrolide compounds and their use in liver stage malaria and related disease (Application number PCT/US2015/046665). E. C. reports research grants from Gilead Sciences and Merck Sharp and Dohme (funds paid to UC Regents), payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Gilead Sciences, and advisory board member for Gilead Sciences. J. C. is aconsultant for Merck and Co. and Resverlogix. S. Ka. reports educational product development for Integritas Communications Group. G. M. reports research grants from Teva, Sanofi Regeneron, Astra Zeneca, Alk Abello, Genentech, Propeller Health, GlaxoSmithKline, and Novartis, and honoraria paid to author for HCPLive educational presentation, and position as Secretary/Treasurer (March 2019 to February 2020), President-Elect (March 2020 to February 2021), President (March 2021 to February 2022) of the American Academy of Allergy, Asthma, and Immunology (payments made to institution during term as President), and Director of American Board of Allergy and Immunology (2020–2025), Co-Chair of American Board of Allergy and Immunology Continuous Assessment Program Examination Committee (2020–2022) (honoraria paid to author). C. S. reports research grants from Centers for Disease Control and Prevention, Merck and Pfizer. D. J. reports grants or contracts unrelated to this work from National Eye Institute, National Institutes of Health, and National Center for Advancing Translational Research, National Institutes of Health; Board of Directors of the American Uveitis Society, speaking honoraria from Retina Society, Controversies in Ophthalmology, University of Rochester, Wills Eye Hospital, LSU School of Medicine and Icahn School of Medicine at Mt. Sinai, and participation on a Data Safety Monitoring Board or Advisory Board for National Eye Institute Intramural Branch. D. Sh. reports numerous grants supporting ongoing and completed research unrelated to this article from the NIH; and is a member of DSMB for the Pelvic Floor Disorders Network (stipend support for meeting activities 4/year). D. H. reports consulting fees from Neurotrope. M. H. reports grants or contracts unrelated to this work from NIH National Center of Advancing Translational Sciences (NCATS) (grant number KL2TR001426), NIH National Institute of Allergy and Infectious Diseases (NIAID) (grant number UM1AI069501), and Insmed Inc, and is a member of the AIDS Clinical Trials Group (ACTG) Tuberculosis Transformative Science Group (TB TSG) Study Monitoring Committee. O. L. reports grants or contracts unrelated to this work from Division of Intramural Research, NIAID, NIH. V. C. reports stock/stock options from spouse’s employer and under spouse’s name from Pfizer. D. T. reports board membership with Excision Bio and board membership (DSMB) with Merck and Co (paid to author); employment with JHU; various expert testimony paid to author; honoraria for CME programs only, paid to author (no service on corporate speaker’s bureau); royalties from UpToDate; and stock/stock options with Excision Bio. N. M. reports participation as HyazOUT and UtahONE combined DSMB member for NIH National Center for Advancing Translational Sciences (NCATS) U24TR001609-S3.All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite rising rates of syphilis among people with human immunodeficiency virus (HIV; PWH) in the United States, there is no optimal syphilis screening frequency or prioritization., Methods: We reviewed records of all PWH in care between 1 January 2014 and 16 November 2018 from 4 sites in the Centers for AIDS Research Network of Integrated Clinical Systems Cohort (CNICS; N = 8455). We calculated rates of syphilis testing and incident syphilis and used Cox proportional hazards models modified for recurrent events to examine demographic and clinical predictors of testing and diagnosis., Results: Participants contributed 29 568 person-years of follow-up. The rate of syphilis testing was 118 tests per 100 person-years (95% confidence interval [CI]: 117-119). The rate of incident syphilis was 4.7 cases per 100 person-years (95% CI: 4.5-5.0). Syphilis diagnosis rates were highest among younger cisgender men who have sex with men and transgender women, Hispanic individuals, people who inject drugs, and those with detectable HIV RNA, rectal infections, and hepatitis C., Conclusions: We identified PWH who may benefit from more frequent syphilis testing and interventions for syphilis prevention., Competing Interests: Potential conflicts of interest. K. C. reports investigator-initiated grant support from Gilead Sciences and serving on Gilead Sciences Medical Advisory Board, outside the submitted work. J. D. reports consulting fees from National Association of State and Territorial AIDS Directors and payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Planned Parenthood Federation of America, outside the submitted work. E. C. reports unrelated research grants, funding paid to UC Regents, from Merck Sharp and Dohme and Gilead Science, outside the submitted work. H. M. C. reports funding from the National Institutes of Health (NIH), the Agency for Healthcare Research and Quality, and ViiV and participation on the NIH Office of AIDS Research Advisory Council, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The incidence of Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) is increasing in the United States; however, there are limited data on anatomic site-specific GC/CT among people with HIV (PWH)., Methods: We reviewed records of all PWH in care between January 1, 2014, and November 16, 2018, at 4 sites in the CFAR Network of Integrated Clinical Systems Cohort (CNICS; n = 8455). We calculated anatomic site-specific GC/CT testing and incidence rates and used Cox proportional hazards models modified for recurrent events to examine sociodemographic and clinical predictors of GC/CT testing and incidence at urogenital, rectal, and pharyngeal sites. We also calculated site-specific number needed to test (NNT) to detect a positive GC/CT test., Results: Of 8455 PWH, 2460 (29.1%) had at least yearly GC/CT testing at any anatomic site. The rates of urogenital, rectal, and pharyngeal GC were 1.7 (95% CI, 1.6-1.9), 3.2 (95% CI, 3.0-3.5), and 2.7 (95% CI, 2.5-2.9) infections per 100 person-years, respectively. The rates of urogenital, rectal, and pharyngeal CT were 1.9 (95% CI, 1.7-2.1), 4.3 (95% CI, 4.0-4.5), and 0.9 (95% CI, 0.8-1.0) infections per 100 person-years, respectively. PWH 16-39 years old experienced greater GC/CT rates at all anatomic sites, while men who have sex with men experienced greater rates of extragenital infections. NNTs for urogenital, rectal, and pharyngeal GC/CT were 20 (95% CI, 19-21), 5 (95% CI, 5-5), and 9 (95% CI, 8-9), respectively., Conclusions: Many PWH are not tested annually for GC/CT, and rates of GC/CT infection, particularly rates of extragenital infections, are high. We identified groups of PWH who may benefit from increased site-specific GC/CT testing., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) worldwide. Although most HPV infections will spontaneously resolve, a considerable proportion of them will persist, increasing the risk of anogenital dysplasia, especially within certain populations, such as patients infected with human immunodeficiency virus (HIV). Furthermore, high-risk oncogenic HPV types (HR-HPV) are the main cause of cervix and other anogenital cancers, such as cancer of the vagina, vulva, penis, or anus. HIV and HPV coinfection is common among people living with HIV (PLWH) but disproportionally affects men who have sex with men (MSM) for whom the rate of persistent HPV infection and reinfection is noteworthy. The molecular interactions between HIV and HPV, as well as the interplay between both viruses and the immune system, are increasingly being understood. The immune dysfunction induced by HIV infection impairs the rate of HPV clearance and increases its oncogenic risk. Despite the availability of effective antiretroviral therapy (ART), the incidence of several HPV-related cancers is higher in PLWH, and the burden of persistent HPV-related disease has become a significant concern in an aging HIV population. Several public health strategies have been developed to reduce the transmission of HIV and HPV and mitigate the consequences of this type of coinfection. Universal HPV vaccination is the most effective preventive tool to reduce the incidence of HPV disease. In addition, screening programs for HPV-related cervical and vulvovaginal diseases in women are well-recognized strategies to prevent cervical cancer. Similarly, anal dysplasia screening programs are being implemented worldwide for the prevention of anal cancer among PLWH. Herein, the main epidemiological features and clinical implications of HIV and HPV coinfection are reviewed, focusing mainly on the relationship between HIV immune status and HPV-related diseases and the current strategies used to reduce the burden of HPV-related disease.

There are no studies comparing the prognosis for mature T-cell lymphoma (TCL) in people with HIV (PWH) to people without HIV (PWoH) and to AIDS-defining B-cell lymphomas (A-BCLs) in the modern antiretroviral therapy era. North American AIDS Cohort Collaboration on Research and Design and Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment are cohorts that enroll patients diagnosed with HIV and TCL, respectively. In our study, 52, 64, 101, 500, and 246 PWH with histologic confirmation of TCL, primary central nervous system lymphoma, Burkitt's lymphoma, diffuse large B-cell lymphoma (DLBCL), and Hodgkin's lymphoma (HL), respectively, and 450 TCLs without HIV were eligible for analysis. At the time of TCL diagnosis, anaplastic large-cell lymphoma (ALCL) was the most common TCL subtype within PWH. Although PWH with TCL diagnosed between 1996 and 2009 experienced a low 5-year survival probability at 0.23 (95% confidence interval [CI]: 0.13, 0.41), we observed a marked improvement in their survival when diagnosed between 2010 and 2016 (0.69; 95% CI: 0.48, 1; P = .04) in contrast to TCLs among PWoH (0.45; 95% CI: 0.41, 0.51; P = .53). Similarly, PWH with ALCLs diagnosed between 1996 and 2009 were associated with a conspicuously inferior 5-year survival probability (0.17; 95% CI: 0.07, 0.42) and consistently lagged behind A-BCL subtypes such as Burkitt's (0.43; 95% CI:0.33, 0.57; P = .09) and DLBCL (0.17; 95% CI: 0.06, 0.46; P = .11) and behind HL (0.57; 95% CI: 0.50, 0.65; P < .0001). Despite a small number, those diagnosed between 2010 and 2016 experienced a remarkable improvement in survival (0.67; 95% CI: 0.3, 1) in comparison with PWoH (0.76; 95% CI: 0.66, 0.87; P = .58). Thus, our analysis confirms improved overall survival for aggressive B- and T-cell malignancies among PWH in the last decade., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Ethics consult services are well established, but often remain underutilized. Our aim was to identify the barriers and perceptions of the Ethics consult service for physicians, advance practice providers (APPs), and nurses at our urban academic medical center which might contribute to underutilization., Methods: This was a cross-sectional single-health system, anonymous written online survey, which was developed by the UCSD Health Clinical Ethics Committee and distributed by Survey Monkey. We compare responses between physicians, APPs, and nurses using standard parametric and non-parametric statistical methods. Satisfaction with ethics consult and likelihood of calling Ethics service again were assessed using a 0-100 scale using a 5-likert response structured (0 being "not helpful at all" to 100 being "extremely helpful") and results presented using box plots and interquartile ranges (IQR)., Results: From January to July 2019, approximately 3800 surveys were sent to all physicians, APPs and nurses with a return rate of 5.5-10%. Although the majority of respondents had encountered an ethical dilemma (85-92.1%) only approximately half had ever requested an Ethics consult. The primary reason for physicians never having requested a consult was that they never felt the need for help (41%). For APPs the primary reasons were not knowing an Ethics consult service was available (33.3%) or not knowing how to contact Ethics (27.8%). For nurses, it was not knowing how to contact the Ethics consult service (30.8%) or not feeling the need for help (26.2%). The median satisfaction score (IQR) for Ethics consult services rated on a 0-100 scale, from physicians was 76 (29), for AAPs 89 (49), and nurses 70 (40) (p = 0.62). The median (IQR) of likelihood of consulting Ethics in the future also on a 0-100 scale was 71 (47) for physicians, 69 (45) for APPs, and 61 (45) for nurses (p = 0.79). APP's and nurses were significantly more likely than physicians to believe that the team did not act on the Ethics consult's recommendations., Conclusions: Based on the results presented, we were able to identify actionable steps to better engage healthcare providers-and in particular APPs and nurses-and scale up institutional educational efforts to increase awareness of the role of the Ethics consult service at our institution. Actionable steps included implementing a system of ongoing feedback that is critical for the sustainability of the Ethics service role. We hope this project can serve as a blueprint for other hospital-based Ethics consult services to improve the quality of their programs.

Importance: People with HIV (PWH) are often coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), leading to increased risk of developing hepatocellular carcinoma (HCC), but few cohort studies have had sufficient power to describe the trends of HCC incidence and risk among PWH in the combination antiretroviral therapy (cART) era., Objective: To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era., Design, Setting, and Participants: This cohort study used data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study, which was conducted between 1996 and 2015. NA-ACCORD pooled individual-level data from 22 HIV clinical and interval cohorts of PWH in the US and Canada. PWH aged 18 years or older with available CD4 cell counts and HIV RNA data were enrolled. Data analyses were completed in March 2020., Exposures: HBV infection was defined as detection of either HBV surface antigen, HBV e antigen, or HBV DNA in serum or plasma any time during observation. HCV infection was defined by detection of anti-HCV seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation., Main Outcomes and Measures: HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage., Results: Of 109 283 PWH with 723 441 person-years of follow-up, the median (interquartile range) age at baseline was 43 (36-51) years, 93 017 (85.1%) were male, 44 752 (40.9%) were White, 44 322 (40.6%) were Black, 21 343 (19.5%) had HCV coinfection, 6348 (5.8%) had HBV coinfection, and 2082 (1.9%) had triple infection; 451 individuals received a diagnosis of HCC by 2015. Between the early (1996-2000) and modern (2006-2015) cART eras, the crude HCC IR increased from 0.28 to 0.75 case per 1000 person-years. HCC IRs remained constant among HIV-monoinfected persons or those coinfected with HBV, but from 1996 to 2015, IRs increased among PWH coinfected with HCV (from 0.34 cases/1000 person-years in 1996 to 2.39 cases/1000 person-years in 2015) or those with triple infection (from 0.65 cases/1000 person-years in 1996 to 4.49 cases/1000 person-years in 2015). Recent HIV RNA levels greater than or equal to 500 copies/mL (IR ratio, 1.8; 95% CI, 1.4-2.4) and CD4 cell counts less than or equal to 500 cells/μL (IR ratio, 1.3; 95% CI, 1.0-1.6) were associated with higher HCC risk in the modern cART era. People who injected drugs had higher HCC risk compared with men who had sex with men (IR ratio, 2.0; 95% CI, 1.3-2.9), adjusted for HBV-HCV coinfection., Conclusions and Relevance: HCC rates among PWH increased significantly over time from 1996 to 2015. PWH coinfected with viral hepatitis, those with higher HIV RNA levels or lower CD4 cell counts, and those who inject drugs had higher HCC risk.

Despite the availability of both effective preventive vaccines and oral antivirals, over 250 million people are chronically infected with the hepatitis B virus (HBV). Globally, chronic hepatitis B is the leading cause of hepatocellular carcinoma, which represents the third cause of cancer mortality, accounting for nearly 1 million annual deaths. Current oral nucleos(t)ide therapy with tenofovir or entecavir suppresses serum HBV-DNA in most treated patients, but rarely is accompanied by HBsAg loss. Thus, treatment has to be given lifelong to prevent viral rebound. A broad spectrum of antivirals that block the HBV life cycle at different steps are in clinical development, including entry inhibitors, cccDNA disrupters/silencers, translation inhibitors, capsid assembly modulators, polymerase inhibitors and secretion inhibitors. Some of them exhibit higher potency than current oral nucleos(t)ides. Drugs in more advanced stages of clinical development are bulevirtide, JNJ-6379, ABI-H0731, ARO-HBV and REP-2139. To date, only treatment with ARO-HBV and with REP-2139 have resulted in HBsAg loss in a significant proportion of patients. Combination therapies using distinct antivirals and/or immune modulators are expected to maximize treatment benefits. The current goal is to achieve a 'functional cure', with sustained serum HBsAg after drug discontinuation. Ultimately, the goal of HBV therapy will be virus eradication, an achievement that would require the elimination of the cccDNA reservoir within infected hepatocytes., Competing Interests: Conflict of interest: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Aramchol, an oral stearoyl-coenzyme-A-desaturase-1 inhibitor, has been shown to reduce hepatic fat content in patients with primary nonalcoholic fatty liver disease (NAFLD); however, its effect in patients with human immunodeficiency virus (HIV)-associated NAFLD is unknown. The aramchol for HIV-associated NAFLD and lipodystrophy (ARRIVE) trial was a double-blind, randomized, investigator-initiated, placebo-controlled trial to test the efficacy of 12 weeks of treatment with aramchol versus placebo in HIV-associated NAFLD. Fifty patients with HIV-associated NAFLD, defined by magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) ≥5%, were randomized to receive either aramchol 600 mg daily (n = 25) or placebo (n = 25) for 12 weeks. The primary endpoint was a change in hepatic fat as measured by MRI-PDFF in colocalized regions of interest. Secondary endpoints included changes in liver stiffness using magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE), and exploratory endpoints included changes in total-body fat and muscle depots on dual-energy X-ray absorptiometry (DXA), whole-body MRI, and cardiac MRI. The mean (± standard deviation) of age and body mass index were 48.2 ± 10.3 years and 30.7 ± 4.6 kg/m 2 , respectively. There was no difference in the reduction in mean MRI-PDFF between the aramchol group at -1.3% (baseline MRI-PDFF 15.6% versus end-of-treatment MRI-PDFF 14.4%, P = 0.24) and the placebo group at -1.4% (baseline MRI-PDFF 13.3% versus end-of-treatment MRI-PDFF 11.9%, P = 0.26). There was no difference in the relative decline in mean MRI-PDFF between the aramchol and placebo groups (6.8% versus 1.1%, P = 0.68). There were no differences in MRE-derived and VCTE-derived liver stiffness and whole-body (fat and muscle) composition analysis by MRI or DXA. Compared to baseline, end-of-treatment aminotransferases were lower in the aramchol group but not in the placebo arm. There were no significant adverse events. Conclusion: Aramchol, over a 12-week period, did not reduce hepatic fat or change body fat and muscle composition by using MRI-based assessment in patients with HIV-associated NAFLD (clinicaltrials.gov ID:NCT02684591)., (© 2019 by the American Association for the Study of Liver Diseases.)

Background: Despite the high prevalence of hepatitis C virus (HCV) among persons living with HIV (PWH), the prevalence of HCV screening, treatment, and sustained virologic response (SVR) is unknown. This study aims to characterize the continuum of HCV screening and treatment among PWH in HIV care., Setting: Adult patients enrolled at 12 sites of the HIV Research Network located in 3 regions of the United States were included., Methods: We examined the prevalence of HCV screening, HCV coinfection, direct-acting antiretroviral (DAA) treatment, and SVR-12 between 2014 and 2015. Multivariate logistic regression was performed to identify characteristics associated with outcomes, adjusted for site., Results: Among 29,071 PWH (age 18-87, 74.8% male, 44.4% black), 77.9% were screened for HCV antibodies; 94.6% of those screened had a confirmatory HCV RNA viral load test. Among those tested, 61.1% were determined to have chronic HCV. We estimate that only 23.4% of those eligible for DAA were prescribed DAA, and only 17.8% of those eligible evidenced initiating DAA treatment. Those who initiated treatment achieved SVR-12 at a rate of 95.2%. Blacks and people who inject drugs (PWID) were more likely to be screened for HCV than whites or those with heterosexual risk. Persons older than 40 years, whites, Hispanics, and PWID [adjusted odds ratio (AOR) 8.70 (7.74 to 9.78)] were more likely to be coinfected than their counterparts. When examining treatment with DAA, persons older than 50 years, on antiretroviral therapy [AOR 2.27 (1.11 to 4.64)], with HIV-1 RNA <400 [AOR 2.67 (1.71 to 4.18)], and those with higher Fib-4 scores were more likely to be treated with DAA., Conclusions: Although rates of screening for HCV among PWH are high, screening remains far from comprehensive. Rates of SVR were high, consistent with previously published literature. Additional programs to improve screening and make treatment more widely available will help reduce the impact of HCV morbidity among PWH.

Background: The availability of direct-acting antivirals (DAA) for the treatment of hepatitis C (HCV) has resulted in the ability to safely and effectively treat patients with cirrhosis and end-stage liver disease. However, information is limited with regard to the impact of DAA treatment on inpatient health-related resource utilization in patients with advanced HCV-related cirrhosis. We aimed to ascertain the impact of DAA treatment on the frequency of liver-related hospitalizations and associated costs in patients with cirrhosis., Patients and Methods: Retrospective cohort analysis carried out at a single US reference center that compared patients with HCV cirrhosis according to treatment status: the untreated group (January 2011 to December 2013) and the DAA-treated group (January 2014 to March 2017). The primary outcome was the difference in the incidence rate of liver-related hospitalizations. Secondary outcomes included differences in the incidence of hepatocellular carcinoma, liver transplant, and all-cause mortality. We calculated the projected savings per-patient treated per-year on the basis of calculated hospitalization rate stratified by Child-Turquotte-Pugh (CTP) score., Results: Baseline characteristics were similar between the untreated (n=182) and DAA-treated (n=196) cohorts. Mean follow-up time in the untreated and treated cohort was 20.4 and 17.7 months, respectively. The incidence rates of liver-related hospitalizations were 29.1/100 and 10.4/100 person-years of follow-up (P≤0.0001) in the untreated and treated cohorts, respectively. This was accounted for by a decreased incidence of hospitalizations in patients with CTP-A (75.8%) and CTP-B (64.5%), but not CTP-C., Conclusion: Successful DAA treatment reduces hospitalization rate and resource utilization costs in patients with CTP-A and CTP-B, but not in those with CTP-C.

Current guidelines specify that visit intervals with viral monitoring should not exceed 6 months for HIV patients. Yet, gaps in care exceeding 6 months are common. In an observational cohort using US patients, we examined the association between gap length and changes in viral load status and sought to determine the length of the gap at which significant increases in viral load occur. We identified patients with gaps in care greater than 6 months from 6399 patients from six US HIV clinics. Gap strata were >6 to <7, 7 to <8, 8 to <9, 9 to <12, and ≥12 months, with viral load measurements matched to the opening and closing dates for the gaps. We examined visit gap lengths in association with two viral load measurements: continuous (log 10 viral load at gap opening and closing) and dichotomous (whether patients initially suppressed but lost viral suppression by close of the care gap). Viral load increases were nonsignificant or modest when gap length was <9 months, corresponding to 10% or fewer patients who lost viral suppression. For gaps ≥12 months, there was a significant increase in viral load as well as a much larger loss of viral suppression (in 23% of patients). Detrimental effects on viral load after a care gap were greater in young patients, black patients, and those without private health insurance. On average, shorter gaps in care were not detrimental to patient viral load status. HIV primary care visit intervals of 6 to 9 months for select patients may be appropriate.

Resistance to direct-acting antiviral (DAA) agents against hepatitis C virus (HCV) infection is driven by the selection of mutations at different positions in the NS3 protease, NS5B polymerase and NS5A proteins. With the exception of NS5B nucleos(t)ide inhibitors, most DAAs possess a low genetic barrier to resistance, with significant cross-resistance between compounds belonging to the same family. However, a specific mutation profile is associated with each agent or drug class and varies depending on the genotype/subtype (e.g., genotype 1b showed higher rates of sustained virological response (SVR) and a higher genetic barrier for resistance than genotype 1a). Moreover, some resistance mutations exist as natural polymorphisms in certain genotypes/subtypes at frequencies that require baseline drug resistance testing before recommending certain antivirals. For example, the polymorphism Q80K is frequently found among genotype 1a (19-48%) and is associated with resistance to simeprevir. Similarly, L31M and Y93H, key resistance mutations to NS5A inhibitors, are frequently found (6-12%) among NS5A genotype 1 sequences. In particular, the presence of these polymorphisms may be of relevance in poorly interferon-responsive patients (i.e., null responders and non-CC IL28B) under DAA-based therapies in combination with pegylated interferon-α plus ribavirin. The relevance of pre-existing resistance mutations for responses to interferon-free DAA therapies is unclear for most regimens and requires further study., (Copyright © 2014 Elsevier B.V. All rights reserved.)