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Hepatitis C virus (HCV) infects an estimated 3% of the global population with the majority of individuals (75-85%) failing to clear the virus without treatment, leading to chronic liver disease. Individuals of African descent have lower rates of clearance compared with individuals of European descent and this is not fully explained by social and environmental factors. This suggests that differences in genetic background may contribute to this difference in clinical outcome following HCV infection. Using 473 individuals and 792,721 single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS), we estimated local African ancestry across the genome. Using admixture mapping and logistic regression, we identified two regions of interest associated with spontaneous clearance of HCV (15q24, 20p12). A genome-wide significant variant was identified on chromosome 15 at the imputed SNP, rs55817928 (P=6.18 × 10(-8)) between the genes SCAPER and RCN. Each additional copy of the African ancestral C allele is associated with 2.4 times the odds of spontaneous clearance. Conditional analysis using this SNP in the logistic regression model explained one-third of the local ancestry association. Additionally, signals of selection in this area suggest positive selection due to some ancestral pathogen or environmental pressure in African, but not in European populations.

Background: U.S. state AIDS Drug Assistance Programs (ADAPs) are federally funded to provide antiretroviral therapy (ART) as the payer of last resort to eligible persons with HIV infection. States differ regarding their financial contributions to and ways

The joint effects of multiple exposures on an outcome are frequently of interest in epidemiologic research. In 2001, Hernán et al (J Am Stat Assoc. 2001;96:440-448) presented methods for estimating the joint effects of multiple time-varying exposures subject to time-varying confounding affected by prior exposure using joint marginal structural models. Nonetheless, the use of these joint models is rare in the applied literature. Minimal uptake of these joint models, in contrast to the now widely used standard marginal structural model, is due in part to a lack of examples demonstrating the method. In this paper, we review the assumptions necessary for unbiased estimation of joint effects as well as the distinction between interaction and effect measure modification. We demonstrate the use of marginal structural models for estimating the joint effects of alcohol consumption and injection drug use on HIV acquisition, using data from 1525 injection drug users in the AIDS Link to Intravenous Experience cohort study. In the joint model, the hazard ratio (HR) for heavy drinking in the absence of any drug injections was 1.58 (95% confidence interval = 0.67-3.73). The HR for any drug injections in the absence of heavy drinking was 1.78 (1.10-2.89). The HR for heavy drinking and any drug injections was 2.45 (1.45-4.12). The P values for multiplicative and additive interaction were 0.7620 and 0.9200, respectively, indicating a lack of departure from effects that multiply or add. We could not rule out interaction on either scale due to imprecision. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) causes substantial morbidity and mortality, particularly among people who inject drugs (PWID). While elimination of HCV as a public health problem may be possible through treatment-as-prevention, reinfection can attenuate the impact of treatment scale-up. There is a need to better understand the distribution and temporal trends in HCV infection risk, including among HCV-seropositive individuals who will be eligible for treatment and at risk for subsequent reinfection. In this analysis of 840 seronegative and seropositive PWID in Baltimore, MD USA, we used random forest methods to develop a composite risk score of HCV infection from sociodemographic and behavioural risk factors. We characterised the individual heterogeneity and temporal trajectories in this composite risk score using latent class methods and compared that index with a simpler, conventional measure, injection drug use frequency. We found that 15% of the population remained at high risk of HCV infection and reinfection by the composite metric for at least 10 years from study enrolment, while others experienced transient periods of moderate and low risk. Membership in this high-risk group was strongly associated with higher rates of HCV seroconversion and post-treatment viraemia, as a proxy of reinfection risk. Injection frequency alone was a poor measure of risk, evidenced by the weak associations between injection frequency classes and HCV-associated outcomes. Together, our results indicate HCV infection risk is not equally distributed among PWID nor well captured by injection frequency alone. HCV elimination programmes should consider targeted, multifaceted interventions among high-risk individuals to reduce reinfection., (© 2024 John Wiley & Sons Ltd.)

Background: For patients with opioid use disorder (OUD), primary care can serve as a pathway to medication for OUD (MOUD). No community-based studies have examined whether people with OUD engaged in primary care are more likely to a) initiate or b) continue MOUD., Methods: Data were collected 2014-2020 from two subsamples of the AIDS Linked to the Intravenous Experience (ALIVE) cohort, a community-recruited cohort of people from Baltimore who have injected drugs: 1) people who reported past-six-month illicit opioid use and no MOUD (360 participants, 789 study visits), and 2) people who reported MOUD and no illicit opioid use in the past six months (561 participants, 2027 visits). Logistic regression was used to estimate associations of past six-month self-reported primary care engagement, respectively, with a) initiating MOUD, b) continuing MOUD, and c) cessation from illicit opioid use without initiating MOUD., Results: Among 360 persons not on MOUD treatment (28 % female, 26 % under 50, 59 % actively injecting drugs), primary care engagement was not associated with either cessation from illicit opioid use or initiating MOUD. Similarly, among persons on MOUD (40 % female, 22 % under 50, 6 % actively injecting drugs) primary care engagement was not associated with continued treatment., Conclusions: Our findings implicate missed opportunities to initiate and maintain buprenorphine treatment in primary care settings., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier B.V.)

HLA class I variation has the strongest effect genome-wide on outcome after HIV infection, and as such, an understanding of the impact of HLA polymorphism on response to HIV vaccination may inform vaccine design. We sought HLA associations with HIV-directed immunogenicity in the phase 1/2a APPROACH vaccine trial, which tested vaccine regimens containing mosaic inserts in Ad26 and MVA vectors, with or without a trimeric gp140 protein. While there were no HLA allelic associations with the overall cellular immune response to the vaccine assessed by ELISpot (Gag, Pol, and Env combined), significant associations with differential response to Gag compared to Env antigens were observed. Notably, HLA class I alleles known to associate with disease susceptibility in HIV natural history cohorts are associated with stronger Env-directed responses, whereas protective alleles are associated with stronger Gag-directed responses. Mean viral loads determined for each HLA allele in untreated individuals correlated negatively with the strength of the Gag response minus the Env response in Black vaccinees based on both ELISpot and CD8 + T cell ICS responses. As the association of T cell responses to conserved Gag epitopes with lower viral load in untreated individuals is well established, our data raise the possibility that the Ad26.Mos.HIV vaccine may induce more effective cellular responses in those with HLA alleles that confer improved virologic control in untreated HIV infection.IMPORTANCENo vaccine tested to date has shown sufficient efficacy against HIV infection. A vaccine that induces robust responses in one individual may fail to do so in another individual due to variation in HLA class I genes, loci central to the immune response. Extensive data have shown the strong effect of HLA variation on outcome after HIV infection, but very little is known about the effect of such variation on HIV vaccine success. Here, we identify a link between the effect of HLA variation on HIV disease outcome and immune responses to an HIV vaccine. HLA variants associated with better HIV control after infection also induce stronger responses against the HIV Gag protein relative to the Env protein after vaccination. Given the virologic control conferred by responses to Gag in natural history of HIV infection, these data suggest that HLA alleles conferring protection after HIV infection may also support a more effective cellular response to HIV vaccination., Competing Interests: J.v.D, M.G.P., D.S., and F.T. are employees of Janssen, and L.L. is a consultant with Johnson & Johnson.

Multimorbidity, defined as having 2 or more chronic conditions, is a growing public health concern, but research in this area is complicated by the fact that multimorbidity is a highly heterogenous outcome. Individuals in a sample may have a differing number and varied combinations of conditions. Clustering methods, such as unsupervised machine learning algorithms, may allow us to tease out the unique multimorbidity phenotypes. However, many clustering methods exist, and choosing which to use is challenging because we do not know the true underlying clusters. Here, we demonstrate the use of 3 individual algorithms (partition around medoids, hierarchical clustering, and probabilistic clustering) and a clustering ensemble approach (which pools different clustering approaches) to identify multimorbidity clusters in the AIDS Linked to the Intravenous Experience cohort study. We show how the clusters can be compared based on cluster quality, interpretability, and predictive ability. In practice, it is critical to compare the clustering results from multiple algorithms and to choose the approach that performs best in the domain(s) that aligns with plans to use the clusters in future analyses., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Given structural barriers, access to services is key for preventing drug-related harms and managing chronic disease among people who inject drugs (PWID). The Patient Activation Measure (PAM), a validated scale to assess self-efficacy in navigating one's own health care, was operationalised to improve service utilisation and outcomes but has not been assessed among PWID. We characterised PAM and its association with healthcare and harm reduction utilisation among PWID in the AIDS Linked to IntraVenous Experience cohort in Baltimore., Methods: From 2019 to 2020, participants completed surveys on PAM, service utilisation and drug use. We used log-binomial regression to identify correlates of "Lower" PAM and modelled the association between lower PAM and service utilisation, stratified by recent IDU., Results: Participants (n = 351) were primarily male (67%), Black (85%) and 24% reported recent IDU. Lower PAM was significantly more common in those reporting IDU (aPR 1.45; 95% CI 1.03, 2.04), heavy alcohol (aPR 1.77; 95% CI 1.24, 2.51) and marijuana (aPR: 1.70; 95% CI 1.23, 2.36) but less common among women (aPR 0.57; 95% CI 0.38, 0.84) and those living with HIV (APR 0.52; 95% CI 0.35, 0.78). In modelling service utilisation, lower PAM was associated with a lower prevalence of methadone utilisation (aPR 0.27; 95% CI 0.09, 0.84) among those reporting IDU, but a higher prevalence of methadone utilisation (aPR 2.72; 95% CI 1.46, 5.08) among those not reporting IDU, after controlling for correlates of PAM., Discussion and Conclusion: PAM-tailored interventions targeting methadone utilisation warrant consideration but should account for socio-structural barriers to utilisation and correlates of PAM among PWID., (© 2024 Australasian Professional Society on Alcohol and other Drugs.)

Background: Chronic hepatitis B virus (HBV) infection is the predominant cause of hepatocellular carcinoma in west Africa, yet data on the incidence of HBV-related hepatocellular carcinoma remain scarce. We aimed to describe the uptake and early outcomes of systematic ultrasound-based hepatocellular carcinoma screening in SEN-B, which is a prospective HBV cohort in Senegal., Methods: In this prospective cohort study, we included treatment-naive, HBsAg-positive individuals who were referred to the two infectious diseases clinics (the Department of Tropical and Infectious Diseases and Ambulatory Treatment Center) at Fann University Hospital of Dakar, Senegal, between Oct 1, 2019, and Oct 31, 2022. All participants resided within the Dakar region. Participants underwent abdominal ultrasound, transient elastography, and clinical and virological assessments at inclusion and every 6 months. Liver lesions at least 1 cm in diameter on ultrasound were assessed using four-phase CT, MRI, or liver biopsy. Adherence to hepatocellular carcinoma surveillance was measured using the proportion of time covered, calculated by dividing the cumulative months covered by abdominal ultrasound examinations by the overall follow-up time, defined as the number of months from the date of cohort entry until the last recorded visit, hepatocellular carcinoma diagnosis, or death. Optimal adherence was defined as a proportion of time covered of 100%., Findings: Overall, 755 (99·6%) of 758 participants had at least one abdominal ultrasound performed. The median age of the enrolled participants was 31 years (IQR 25-39), 355 (47·0%) of 755 participants were women, and 82 (10·9%) had a family history of hepatocellular carcinoma. 15 (2·0%) of 755 individuals were HBeAg positive, 206 (27·3%) of 755 individuals had HBV DNA of more than 2000 IU/mL, and 27 (3·6%) of 755 had elastography-defined liver cirrhosis. Of ten (1·3%) participants with a focal lesion at least 1 cm at initial assessment, CT or MRI ruled out hepatocellular carcinoma in nine, whereas imaging and subsequent liver biopsy confirmed one patient with hepatocellular carcinoma. Two further patients with hepatocellular carcinoma were diagnosed at study presentation due to the presence of portal thrombosis on ultrasound. Excluding the three participants with hepatocellular carcinoma identified at baseline, 752 participants were eligible for screening every 6 months. Median follow-up time was 12 months (IQR 6-18) and the median number of ultrasounds per patient was 3 (2-4). During 809·5 person-years of follow-up, one incident hepatocellular carcinoma was reported, resulting in an incidence rate of 1·24 cases per 1000 person-years (95% CI 0·18-8·80). Overall, 702 (93·0%) of 755 participants showed optimal hepatocellular carcinoma surveillance, but this proportion decreased to 77·8% (42 of 54 participants) after 24 months., Interpretation: Hepatocellular carcinoma screening is feasible in HBV research cohorts in west Africa, but its longer-term acceptability needs to be evaluated. Long-term hepatocellular carcinoma incidence data are crucial for shaping tailored screening recommendations., Funding: Swiss National Science Foundation, the Swiss Cancer Research Foundation, the National Cancer Institute, and Roche Diagnostics., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests GW has received research grants from Roche Diagnostics and Gilead Sciences, and served in advisory boards for ViiV, Gilead Sciences, and Merck & Co. AB reports consulting fees from Inventiva and grant support from Boehringer Ingelheim. All other authors declare no competing interests., (Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

After recovery from a hepatitis B virus (HBV) infection, reactivation can occur with immunosuppression; thus, it is assumed that replication competent HBV persists in the liver. We sought to detect persistent HBV from 13 people with spontaneous recovery. We quantified HBV DNA and RNA in core liver biopsies (median 1.72x106 cells) from people who inject drugs (PWID). Among 13 biopsies, 8 (61%) had evidence of HBV DNA or RNA and 5 (38%) had both HBV DNA and RNA. mRNAs derived from cccDNA and integrated HBV DNA. Here, we show prevalent HBV DNA and RNA despite clinical recovery in PWID., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Substance use disorder treatment and recovery support services are critical for achieving and maintaining recovery. There are limited data on how structural and social changes due to the COVID-19 pandemic impacted individual-level experiences with substance use disorder treatment-related services among community-based samples of people who inject drugs., Methods: People with a recent history of injection drug use who were enrolled in the community-based AIDS Linked to the IntraVenous Experience study in Baltimore, Maryland participated in a one-time, semi-structured interview between July 2021 and February 2022 about their experiences living through the COVID-19 pandemic (n = 28). An iterative inductive coding process was used to identify themes describing how structural and social changes due to the COVID-19 pandemic affected participants' experiences with substance use disorder treatment-related services., Results: The median age of participants was 54 years (range = 24-73); 10 (36%) participants were female, 16 (57%) were non-Hispanic Black, and 8 (29%) were living with HIV. We identified several structural and social changes due the pandemic that acted as barriers and facilitators to individual-level engagement in treatment with medications for opioid use disorder (MOUD) and recovery support services (e.g., support group meetings). New take-home methadone flexibility policies temporarily facilitated engagement in MOUD treatment, but other pre-existing rigid policies and practices (e.g., zero-tolerance) were counteracting barriers. Changes in the illicit drug market were both a facilitator and barrier to MOUD treatment. Decreased availability and pandemic-related adaptations to in-person services were a barrier to recovery support services. While telehealth expansion facilitated engagement in recovery support group meetings for some participants, other participants faced digital and technological barriers. These changes in service provision also led to diminished perceived quality of both virtual and in-person recovery support group meetings. However, a facilitator of recovery support was increased accessibility of individual service providers (e.g., counselors and Sponsors)., Conclusions: Structural and social changes across several socioecological levels created new barriers and facilitators of individual-level engagement in substance use disorder treatment-related services. Multilevel interventions are needed to improve access to and engagement in high-quality substance use disorder treatment and recovery support services among people who inject drugs., (© 2024. The Author(s).)

Background: As antiretroviral therapy has become widely available and highly effective, HIV has evolved to a manageable, chronic disease. Despite this health advancement, people living with HIV (PLWH) are at an increased risk for age-related non-communicable diseases (NCDs) compared to HIV-uninfected individuals. Similarly, PLWH are at an increased risk for selected oral diseases. PLWH with a history of injecting drugs experience an even greater burden of disease than their counterparts. The overall objective of the Baltimore Oral Epidemiology, Disease Effects, and HIV Evaluation (BEEHIVE) study is to determine the combined effects of HIV infection and NCDs on oral health status. The specific aims of the study are to: (1) determine to what extent HIV status influences access to and utilization of oral health care services; (2) determine to what extent HIV status affects self-reported and clinical oral health status; (3) determine to what extent HIV status influences the progression of periodontitis; and (4) determine to what extent HIV status impacts the periodontitis-associated oral microbiome signature., Methods: The BEEHIVE study uses a prospective cohort study design to collect data from participants at baseline and at a 24-month follow-up visit. Data are collected through questionnaire assessments, clinical examinations, and evaluation of oral microbiological samples to determine the drivers of oral disease among a high-risk population of PLWH with a history of injection drug use and prevalent comorbid NCDs. The established AIDS Linked to the Intravenous Experience (ALIVE) cohort serves as the source of participants for the BEEHIVE Study., Discussion: Upon completion of the BEEHIVE study, the knowledge gained will be important in informing future clinical and preventive interventions that can be implemented into medical and dental practice to ultimately help eliminate long-standing oral health inequities that PLWH experience., (© 2024. The Author(s).)

Background: Overdoses involving opioids and stimulants are on the rise, yet few studies have examined longitudinal trends in use of both substances. We sought to describe use and co-use of opioids and stimulants, 2005-2019, in the AIDS Linked to the Intravenous Experience (ALIVE) cohort - a community-based cohort of people with a history of injection drug use living in or near Baltimore, MD., Methods: We included 2083 ALIVE participants, who had at least two visits during the study period. Our outcome was based on self-reported use of opioids and stimulants in the prior 6 months. We estimated prevalence of 4 categories of use (neither stimulants nor opioids, only stimulants, only opioids, stimulants and opioids), using a non-parametric multi-state model, accounting for the competing event of death and weighting for informative loss to follow-up. All analyses were stratified by enrollment cohort, with the main analysis including participants who enrolled prior to 2015 and a sub-analysis including participants who enrolled 2015-2018., Results: In the main analysis, prevalence of using stimulants and opioids decreased from 38 % in 2005 to 12 % 2013 but stabilized from 2014 onwards (13-19 %). The prevalence of using only stimulants (7-11 %) and only opioids (5-10 %) was stable across time. Participants who reported using both were more likely to report homelessness, depression, and other substance use (e.g., marijuana and heavy alcohol use) than participants in the other use categories. On average, 65 % of visits with use of both were followed by a subsequent visit with use of both; of participants transitioning out of using both, 13% transitioned to using neither., Conclusions: While use of stimulants and opioids declined in the cohort through 2013, a meaningful proportion of participants persistently used both. More research is needed to understand and develop strategies to mitigate harms associated with persistent use of both stimulants and opioids., 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., (Copyright © 2024. Published by Elsevier B.V.)

Background: Delay discounting quantifies an individual's preference for smaller, short-term rewards over larger, long-term rewards and represents a transdiagnostic factor associated with numerous adverse health outcomes. Rather than a fixed trait, delay discounting may vary over time and place, influenced by individual and contextual factors. Continuous, real-time measurement could inform adaptive interventions for various health conditions., Objective: The goals of this paper are 2-fold. First, we present and validate a novel, short, ecological momentary assessment (EMA)-based delay discounting scale we developed. Second, we assess this tool's ability to reproduce known associations between delay discounting and health behaviors (ie, substance use and craving) using a convenience-based sample., Methods: Participants (N=97) were adults (age range 18-71 years), recruited on social media. In phase 1, data were collected on participant sociodemographic characteristics, and delay discounting was evaluated via the traditional Monetary Choice Questionnaire (MCQ) and our novel method (ie, 7-item time-selection and 7-item monetary-selection scales). During phase 2 (approximately 6 months later), participants completed the MCQ, our novel delay discounting measures, and health outcomes questions. The correlations between our method and the traditional MCQ within and across phases were examined. For scale reduction, a random number of items were iteratively selected, and the correlation between the full and random scales was assessed. We then examined the association between our time- and monetary-selection scales assessed during phase 2 and the percentage of assessments that participants endorsed using or craving alcohol, tobacco, or cannabis., Results: In total, 6 of the 7 individual time-selection items were highly correlated with the full scale (r>0.89). Both time-selection (r=0.71; P<.001) and monetary-selection (r=0.66; P<.001) delay discounting rates had high test-retest reliability across phases 1 and 2. Phase 1 MCQ delay discounting function highly correlated with phase 1 (r=0.76; P<.001) and phase 2 (r=0.45; P<.001) time-selection delay discounting scales. One or more randomly chosen time-selection items were highly correlated with the full scale (r>0.94). Greater delay discounting measured via the time-selection measure (adjusted mean difference=5.89, 95% CI 1.99-9.79), but not the monetary-selection scale (adjusted mean difference=-0.62, 95% CI -3.57 to 2.32), was associated with more past-hour tobacco use endorsement in follow-up surveys., Conclusions: This study evaluated a novel EMA-based scale's ability to validly and reliably assess delay discounting. By measuring delay discounting with fewer items and in situ via EMA in natural environments, researchers may be better able to identify individuals at risk for poor health outcomes., (©Amanda Luken, Jill A Rabinowitz, Jonathan L Wells, David W Sosnowski, Justin C Strickland, Johannes Thrul, Gregory D Kirk, Brion S Maher. Originally published in JMIR Formative Research (https://formative.jmir.org), 27.02.2024.)

The relationships between place (e.g., neighborhood) and HIV are commonly investigated. As measurements of place are multivariate, most studies apply some dimension reduction, resulting in one variable (or a small number of variables), which is then used to characterize place. Typical dimension reduction methods seek to capture the most variance of the raw items, resulting in a type of summary variable we call "disadvantage score". We propose to add a different type of summary variable, the "vulnerability score," to the toolbox of the researchers doing place and HIV research. The vulnerability score measures how place, as known through the raw measurements, is predictive of an outcome. It captures variation in place characteristics that matters most for the particular outcome. We demonstrate the estimation and utility of place-based vulnerability scores for HIV viral non-suppression, using data with complicated clustering from a cohort of people with histories of injecting drugs., (© 2024. The Author(s).)

Heterozygosity of Human leukocyte antigen ( HLA ) class I genes is linked to beneficial outcomes after HIV infection, presumably through greater breadth of HIV epitope presentation and cytotoxic T cell response. Distinct allotype pairs, however, differ in the extent to which they bind shared sets of peptides. We developed a functional divergence metric that measures pairwise complementarity of allotype-associated peptide binding profiles. Greater functional divergence for pairs of HLA-A and/or HLA-B allotypes was associated with slower AIDS progression and independently with enhanced viral load control. The metric predicts immune breadth at the peptide level rather than gene level and redefines HLA heterozygosity as a continuum differentially affecting disease outcome. Functional divergence may affect response to additional infections, vaccination, immunotherapy, and other diseases where HLA heterozygote advantage occurs.

Background: Estimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030., Methods and Findings: Using the PEARL model-an agent-based simulation of PWH who have initiated ART in the US-the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information). In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19% heterosexual women. Additionally, 44% were Black/AA, 32% White, and 23% Hispanic. Along with a gradual rise in population size of PWH receiving ART-reaching 908,000 individuals by 2030-PEARL forecasted a surge in prevalence of most comorbidities to 2030. Depression and/or anxiety was high and increased from 60% in 2020 to 64% in 2030. Hypertension decreased while dyslipidemia, diabetes, CKD, and MI increased. There was little change in prevalence of cancer and ESLD. The forecasted multimorbidity among PWH receiving ART increased from 63% in 2020 to 70% in 2030. There was heterogeneity in trends across subgroups. Among Black women with history of injection drug use in 2030 (oldest demographic subgroup with median age of 66 year), dyslipidemia, CKD, hypertension, diabetes, anxiety, and depression were most prevalent, with 92% experiencing multimorbidity. Among Black MSM in 2030 (youngest demographic subgroup with median age of 42 year), depression and CKD were highly prevalent, with 57% experiencing multimorbidity. These results are limited by the assumption that trends in new HIV diagnoses, mortality, and comorbidity risk observed in 2009 to 2017 will persist through 2030; influences occurring outside this period are not accounted for in the forecasts., Conclusions: The PEARL forecasts suggest a continued rise in comorbidity and multimorbidity prevalence to 2030, marked by heterogeneities across race/ethnicity, gender, and HIV acquisition risk subgroups. HIV clinicians must stay current on the ever-changing comorbidities-specific guidelines to provide guideline-recommended care. HIV clinical directors should ensure linkages to subspecialty care within the clinic or by referral. HIV policy decision-makers must allocate resources and support extended clinical capacity to meet the healthcare needs of people aging with HIV., Competing Interests: KNA serves on the scientific review board for TrioHealth Inc and as a consultant to the All of Us Research Program. MJG has been an Hoc member on national HIV Advisory Boards of Merck, Gilead and ViiV. CW is currently employed by Regeneron Pharmaceuticals Inc and contributed to this article as a prior trainee of Johns Hopkins University. KG declares that his institution receives funding from U.S. Department of Defense’s (DOD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), in collaboration with the Defense Health Agency (DHA) (contract number: W911QY2090012), Bloomberg Philanthropies, State of Maryland, NIH National Center for Advancing Translational Sciences (NCATS) U24TR001609, Division of Intramural Research NIAID NIH, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation for her work. KG received royalties from UptoDate and served as a paid consultant to Aspen Institute, and Teach for America. KG declares that none of these funding sources are related to this manuscript. PFR declares consultation with Gilead & Janssen pharmaceuticals (money paid to individual); research grants from NIH/NIAID (money paid to institution). JT declares to be consultant for AbbVie, Canfield, Gilead, Roche and Tarsier and being Equity owner for Tarsier. VFM has received support from the Emory CFAR (P30 AI050409) and received investigator-initiated research grants (to the institution) and consultation fees (both unrelated to the current work) from Eli Lilly, Bayer, Gilead Sciences, and ViiV. HNK declares that Gilead Sciences program funding paid to the author’s institution. The following authors have declared that no competing interests exist: CS, EH, LG, CB, ACJ, EH, SC, RL, MJS, MH, VL, MK, AJR, HC, MK, AR, SL, GDS, SN, KMG, GDK, TRS, RDM, PK., (Copyright: © 2024 Althoff et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Real-world evidence of coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) booster effectiveness among patients with immune dysfunction are limited., Methods: We included data from patients in the United States National COVID Cohort Collaborative (N3C) who completed ≥2 doses of mRNA vaccination between 10 December 2020 and 27 May 2022. Immune dysfunction conditions included human immunodeficiency virus infection, solid organ or bone marrow transplant, autoimmune diseases, and cancer. We defined incident COVID-19 BTI as positive results from laboratory tests or diagnostic codes 14 days after at least 2 doses of mRNA vaccination; and severe COVID-19 BTI as hospitalization, invasive cardiopulmonary support, and/or death. We used propensity scores to match boosted versus nonboosted patients and evaluated hazards of incident and severe COVID-19 BTI using Cox regression after matching., Results: Among patients without immune dysfunction, the relative effectiveness of booster (3 doses) after 6 months from the primary (2 doses) vaccination against BTI ranged from 69% to 81% during the Delta-predominant period and from 33% to 39% during the Omicron-predominant period. Relative effectiveness against BTI was lower among patients with immune dysfunction but remained statistically significant in both periods. Boosted patients had lower risk of COVID-19-related hospitalization (hazard ratios [HR] ranged from 0.5 [95% confidence interval {CI}, .48-.53] to 0.63 [95% CI, .56-.70]), invasive cardiopulmonary support, or death (HRs ranged from 0.46 [95% CI, .41-.52] to 0.63 [95% CI, .50-.79]) during both periods., Conclusions: Booster vaccines remain effective against severe COVID-19 BTI throughout the Delta- and Omicron-predominant periods, regardless of patients' immune status., Competing Interests: Potential conflicts of interest. J. Y. I. reports receiving consulting fees from Flatiron Health. D. S. reports receiving honoraria from Sanofi, Novartis, Veloxis, Mallinckrodt, Jazz Pharmaceuticals, CSL Behring, Thermo Fisher Scientific, Caredx, Transmedics, Kamada, MediGO, Regeneron, AstraZeneca, Takeda, and Bridge to Life. R. B. M. reports receiving honoraria from Vitaeris and Olaris and grant support from VericiDx. J. A. S. reports receiving personal fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two Labs Inc, Adept Field, Solutions, Clinical Care Options, ClearView, Healthcare Partners, Putnam Associates, Focus Forward, Navigant, Spherix, MedIQ, Jupiter Life, Science, UBM LLC, Trio Health, Medscape, WebMD, Practice Point Communications, National Institutes of Health, American College of Rheumatology, and Simply Speaking; and holds stock options from TPT Global Tech, Vaxart, Atyu Biopharma, and Charlotte's Web Holdings, outside the submitted work. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background:  People with a history of injection drug use face discrimination in healthcare settings that may impede their use of routine care, leading to greater reliance on the emergency department (ED) for addressing health concerns. The relationship between discrimination in healthcare settings and subsequent ED utilization has not been established in this population., Methods:  This analysis used longitudinal data collected between January 2014 and March 2020 from participants of the ALIVE (AIDS Linked to the IntraVenous Experience) study, a community-based observational cohort study of people with a history of injection drug use in Baltimore, Maryland. Logistic regressions with generalized estimating equations were used to estimate associations between drug use-related discrimination in healthcare settings and subsequent ED utilization for the sample overall and six subgroups based on race, sex, and HIV status., Results:  1,342 participants contributed data from 7,289 semiannual study visits. Participants were predominately Black (82%), mostly male (66%), and 33% were living with HIV. Drug use-related discrimination in healthcare settings (reported at 6% of study visits) was positively associated with any subsequent ED use (OR = 1.40, 95% CI: 1.15-1.72). Positive associations persisted after adjusting for covariates, including past sixth-month ED use and drug use, among the overall sample (aOR = 1.28, 95% CI: 1.04-1.59) and among some subgroups., Conclusions:  Drug use-related discrimination in healthcare settings was associated with greater subsequent ED utilization in this sample. Further exploration of mechanisms driving this relationship may help improve care and optimize healthcare engagement for people with a history of injection drug use.

Background: Although hepatitis C virus (HCV) can be cured by direct acting antivirals (DAA), uptake is not well characterized for people who inject drugs (PWID)., Methods: Among 1,130 participants of a community-based cohort of PWID with chronic HCV, we longitudinally characterized HCV treatment uptake and cure early (2014-2016) and later (2017-2020)., Results: Cumulative HCV treatment uptake increased from 4% in 2014 to 68% in 2020 and the percent with HCV viremia declined from nearly 100% to 33%. Predictors of treatment uptake varied across periods. Age (incidence rate ratio [IRR] per 5-year increase: 1.28; 95% confidence interval [CI]: 1.15, 1.42), educational attainment (IRR for ≥ high school diploma: 1.31; 95% CI: 1.04, 1.66), HIV coinfection with suppressed viral load (IRR vs. HIV negative: 2.08; 95% CI: 1.63, 2.66) and alcohol dependence (IRR vs. no alcohol use: 0.63; 95% CI: 0.43, 0.91) were associated with treatment uptake in the early period, but not later. HIV coinfection with a detectable viral load (IRR vs. HIV negative: 0.46; 95% CI: 0.23, 0.95) and daily injecting (IRR: 0.46 vs. no injection; 95% CI: 0.27, 0.79) were significantly associated with lower treatment uptake later. Homelessness was associated with significantly reduced likelihood of viral clearance in the late DAA era (IRR: 0.51; 95% CI: 0.30, 0.88)., Conclusion: Treatment uptake improved substantially in this cohort of PWID in the first five years of DAA availability with commensurate declines in viremia. Additional efforts are needed to treat those actively injecting and unstably housed in order to realize elimination goals., Competing Interests: Conflict of Interest DT: medical editing for UpToDate; scientific advisor to Excision Bio, Evrys Bio, and Merck. OFN research grants from Abbvie paid to institution; scientific consulting for Gilead. SM: materials support from Abbott. Other authors: no conflict declared.

We evaluated the prospective association of mitochondrial DNA copy number (mtDNA CN) with markers of kidney function among a cohort of persons who inject drugs (PWID). This is a Prospective cohort study nested in the AIDS linked to the intravenous experience cohort (community-based cohort of PWID in Baltimore, MD). mtDNA CN was measured at two time-points 5 years apart using a real-time polymerase chain reaction. Kidney function (estimated glomerular filtration rate [eGFR], serum creatinine, urine protein) was measured annually. We used linear mixed effects models to evaluate kidney function trajectories (N = 946) and Cox regression models to assess hazard of incident CKD (eGFR < 60 at two consecutive visits, N = 739) and proteinuria (urine protein:creatinine ratio > 200, N = 573) by level of mtDNA CN (Low [lowest quartile], vs high [other three quartiles]. Models were adjusted for demographic and behavioral characteristics, HIV and/or HCV infection, and comorbidity burden. Low mtDNA CN was independently associated with higher hazard of incident CKD (aHR: 2.33, 95% CI 1.42, 3.80) and proteinuria (aHR: 1.42, 95% CI 1.04, 1.96). Participants with low mtDNA CN had greater declines in eGFR and greater increases in serum creatinine over time. Low mtDNA CN is associated with more rapid kidney function decline and risk of incident CKD and proteinuria., (© 2023. The Author(s).)

Low-cost air quality monitors are growing in popularity among both researchers and community members to understand variability in pollutant concentrations. Several studies have produced calibration approaches for these sensors for ambient air. These calibrations have been shown to depend primarily on relative humidity, particle size distribution, and particle composition, which may be different in indoor environments. However, despite the fact that most people spend the majority of their time indoors, little is known about the accuracy of commonly used devices indoors. This stems from the fact that calibration data for sensors operating in indoor environments are rare. In this study, we sought to evaluate the accuracy of the raw data from PurpleAir fine particulate matter monitors and for published calibration approaches that vary in complexity, ranging from simply applying linear corrections to those requiring co-locating a filter sample for correction with a gravimetric concentration during a baseline visit. Our data includes PurpleAir devices that were co-located in each home with a gravimetric sample for 1-week periods (265 samples from 151 homes). Weekly-averaged gravimetric concentrations ranged between the limit of detection (3 μg/m 3 ) and 330 μg/m 3 . We found a strong correlation between the PurpleAir monitor and the gravimetric concentration (R>0.91) using internal calibrations provided by the manufacturer. However, the PurpleAir data substantially overestimated indoor concentrations compared to the gravimetric concentration (mean bias error ≥ 23.6 μg/m 3 using internal calibrations provided by the manufacturer). Calibrations based on ambient air data maintained high correlations (R ≥ 0.92) and substantially reduced bias (e.g. mean bias error = 10.1 μg/m 3 using a US-wide calibration approach). Using a gravimetric sample from a baseline visit to calibrate data for later visits led to an improvement over the internal calibrations, but performed worse than the simpler calibration approaches based on ambient air pollution data. Furthermore, calibrations based on ambient air pollution data performed best when weekly-averaged concentrations did not exceed 30 μg/m 3 , likely because the majority of the data used to train these models were below this concentration., Competing Interests: Declaration of interests 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.

We evaluated geographic heterogeneity in hepatitis C virus (HCV) treatment penetration among people who inject drug (PWID) across Baltimore, MD since the advent of direct-acting antivirals (DAAs) using space-time clusters of HCV viraemia. Using data from a community-based cohort of PWID, the AIDS Linked to the IntraVenous Experience (ALIVE) study, we identified space-time clusters with higher-than-expected rates of HCV viraemia between 2015 and 2019 using scan statistics. We used Poisson regression to identify covariates associated with HCV viraemia and used the regression-fitted values to detect adjusted space-time clusters of HCV viraemia in Baltimore city. Overall, in the cohort, HCV viraemia fell from 77% in 2015 to 64%, 49%, 39% and 36% from 2016 to 2019. In Baltimore city, the percentage of census tracts where prevalence of HCV viraemia was ≥85% dropped from 57% to 34%, 25%, 22% and 10% from 2015 to 2019. We identified two clusters of higher-than-expected HCV viraemia in the unadjusted analysis that lasted from 2015 to 2017 in East and West Baltimore and one adjusted cluster of HCV viraemia in West Baltimore from 2015 to 2016. Neither differences in age, sex, race, HIV status, nor neighbourhood deprivation were able to explain the significant space-time clusters. However, residing in a cluster with higher-than-expected viraemia was associated with age, sex, educational attainment and higher levels of neighbourhood deprivation. Nearly 4 years after DAAs became available, HCV treatment has penetrated all PWID communities across Baltimore city. While nearly all census tracts experienced improvements, change was more gradual in areas with higher levels of poverty., (© 2023 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Background: Overdose deaths increased during the COVID-19 pandemic in the United States. Less is known about drug use behavior changes during the same time period. We examined differences in non-fatal overdose and drug use behaviors before and after the start of the COVID-19 pandemic in a community-recruited cohort of adults who have injected drugs., Methods: 721 participants attended 7401 visits between Jan 2014 and Mar 2022. Outcomes (non-fatal overdose, drug route of administration, type of drugs used) were assessed via self-report in the last six months. We compared pre-pandemic (Jan 2014-Mar 2020) to inter-pandemic (Dec 2020-Mar 2022) prevalence of each outcome using Cohcrane-Maentel-Haeszel odds ratios (CMH-OR). We then estimated probabilities for transitioning between specific behaviors from participants' last pre-pandemic visit to their first inter-pandemic visit., Results: Comparing pre-pandemic visits to inter-pandemic visits, the prevalence of non-fatal overdose did not change (CMH-OR 1.06, 95% CI 0.75-1.50); the prevalence of injection (CMH-OR 0.13, 95% CI 0.1-0.17) and non-injection (CMH-OR 0.51, 95% CI 0.42-0.61) drug use declined. More than a third (35.7%) of persons using both injection and non-injection drugs pre-pandemic transitioned to exclusive non-injection use during the pandemic. By contrast, few (4.0%) persons using non-injection drugs exclusively pre-pandemic transitioned to injecting during the pandemic., Conclusion: Among adults who have injected drugs, the start of the COVID-19 pandemic was associated with a reduced drug use prevalence and transitions from injection to non-injection use. Average overdose prevalence was unchanged, but these behavior changes may have helped mitigate overdose harm., Competing Interests: Declaration of Competing Interest No conflict declared, (Copyright © 2023. Published by Elsevier B.V.)

People who inject drugs (PWID) may have diminished access to essential preventive services like COVID-19 vaccination given structural and substance use barriers. We aimed to assess the role of HIV on COVID-19 vaccination uptake among adult PWID participating in the ALIVE cohort study in Baltimore, Maryland who were alive as of April 2021. We abstracted COVID-19 vaccination data from electronic medical records via the regional health information exchange. We used Kaplan-Meier method to estimate time from universal vaccine eligibility (April 6, 2021) to completion of the COVID-19 vaccination primary series (1 dose J&J or 2 doses mRNA) by HIV viral load status (uninfected, PWH [HIV-RNA < 400 copies/mL], PWH [HIV-RNA ≥ 400 copies/mL]) and Cox Proportional Hazards regression to adjust for potential confounders. Our sample (N = 960) was primarily black (77%) and male (65%) with 31% reporting recent injection drug use. Among 265 (27%) people living with HIV (PWH) in our sample, 84% were virally suppressed. As of February 22, 2022, 539 (56%) completed the primary series, 131 (14%) received a single dose of mRNA vaccine and 290 (30%) remained unvaccinated. Compared to PWID without HIV, virally suppressed PWH were more likely to complete the primary series (Adjusted Hazard Ratio [aHR]:1.23,95% Confidence Interval [95 %CI]:1.07,1.50), while PWH who were not virally suppressed were less likely (aHR:0.72,95 %CI:0.45,1.16), although this was not statistically significant. We conclude that among PWID, HIV infection and viral suppression is associated with quicker vaccination uptake, likely due to HIV care engagement. Targeted improvements along the HIV care continuum may bolster vaccine uptake., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier Inc.)

A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step., Competing Interests: J.T. reports grants to her institution from the City of Philadelphia ID/SUD Care Integration Pilot. K.N.A. reports grants to her institution from the National Institute of Health (NIH), royalties from Coursera, and consulting fees from NIH and TrioHealth. M.B.K. reports grants from Canadian Institutes of Health Research, Fonds de recherché Quebec –Sante, NIH, ViiV Health Care, Gilead Sciences, and Abbvie; consulting fees from ViiV Health Care, Gilead Sciences, and Abbvie; leadership role in the CIHR Canadian HIV Trials Network; and receipt of goods/services from Siga Technologies. K.R.R. reports grants to his institution from Mallinckrodt, Exact Sciences, BMS, Intercept, Merck, Gilead, Grifols, Sequana, HCC-TARGET, NASH-TARGET, and BioVie; royalties from UpToDate; consulting fees from Spark Therapeutics, Mallinckrodt, Genfit, and Novo Nordisk; paid board participation from Novartis; and leadership roles in Gastroenterology and AASLD Task Force for COVID Activities. E.R.C. reports grants to his institution from Gilead Sciences and board participation in THERAtechnologies. J.K.L. reports grants to his institution from Intercept, Gilead, Viking, Pfizer, Eiger, Inventiva, and Novo Nordisk and leadership roles in the American Association for Study of Liver Diseases, American Gastroenterological Association, and American College of Gastroenterology. M.J.G. reports participation on the HIV national advisory boards for Merck, Gilead, and Viiv. K.C. reports grants to her institution from Merck Sharp & Dohme and Amgen; consulting fees from Pardes Bioscences; honoraria payments from International Antiviral Society-USA; and participation in the UCSF Safety Monitoring Committee. M.H. reports grants from Gilead Life Science for an investigator initiated study and participation in the data safety monitoring board for the M2HepPreP study. G.D.K. reports grants to his institution from NIH. K.A.G. reports grants to her institution from NIH, US Department of Defense, Defense Health Agency, State of Maryland, Octapharma, Mental Wellness Foundation, HealthNetwork Foundation, Bloomberg Philanthropies, and Moriah Fund; royalties from UpToDate; consulting fees from Spark HealthCare, Teach for America, and Aspen Institute; and unpaid advisor participation on a Pfizer scientific advisory board. H.N.K. reports grants to her institution from Gilead Sciences. V.L.R. reports grants to his institution from NIH and a leadership role in the International Society for Pharmacoepidemiology. All other authors reported no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: The social processes around initiating injection may be well-suited to intervention, yet there is substantial heterogeneity in the reported experiences of people who inject drugs (PWID) who assist with another individual's first drug injection. We aimed to describe the lifetime prevalence and context of providing initiation assistance among a cohort of PWID., Methods: Participants of the AIDS Linked to the IntraVenous Experience (ALIVE) cohort of PWID in Baltimore, Maryland (n=848) were surveyed during 2019-2020 about assisting with another person's first injection. Associations between factors related to injection risk and history of providing assistance were estimated using logistic regression models adjusted for sociodemographic and behavioral characteristics., Results: At baseline, participants were primarily male (66.1%), black (82.9%), aged a median of 42 years, and had been injecting a median of 18 years. Overall, 19% (n=157) of participants reported ever providing assistance for a median of 2 people (Interquartile Range: 1-4). Having hepatitis C infection (adjusted Odds Ratio [95% Confidence Interval]: 2.5 [1.4-4.6]), syringe sharing (2.2 [1.2-3.9]), and injecting ≥3 times per day (2.0 [1.2-3.4]) at study enrollment were associated with a history of assistance. Participants primarily assisted friends (58.0%), acquaintances (29.9%), and partners (21.7%). Common reasons for assisting were the other person's lack of injection knowledge (73.7%) or sharing drugs (44.9%). Additional reasons included to prevent injury., Conclusion: PWID with a history of assisting with another person's first injection exhibited heightened vulnerability to infections and more frequent substance use. Expanding implementation of interventions with an emphasis on harm reduction is needed., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: SARS-CoV-2 serosurveys can help characterize disparities in SARS-CoV-2 infection and identify gaps in population immunity. Data on SARS-CoV-2 seroprevalence among people who inject drugs (PWID) are limited., Methods: We conducted a cross-sectional study between December 2020 and July 2022 among 561 participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study-a community-based cohort of current and former PWID in Baltimore, Maryland. Serum samples were assayed for infection-induced anti-nucleocapsid (anti-N) and infection and/or vaccination-induced anti-spike-1 (anti-S) SARS-CoV-2 IgG. We estimated adjusted prevalence ratios (aPR) via modified Poisson regression models., Results: The median age was 59 years, 35% were female, 84% were non-Hispanic Black, and 16% reported recent injection drug use. Anti-N antibody prevalence was 26% and anti-S antibody prevalence was 63%. Anti-N and anti-S antibody prevalence increased over time. Being employed (aPR=1.53 [95%CI=1.11-2.11]) was associated with higher anti-N prevalence, while a cancer history (aPR=0.40 [95%CI=0.17-0.90]) was associated with lower anti-N prevalence. HIV infection was associated with higher anti-S prevalence (aPR=1.13 [95%CI=1.02-1.27]), while younger age and experiencing homelessness (aPR=0.78 [95%CI=0.60-0.99]) were factors associated with lower anti-S prevalence. Substance use-related behaviors were not significantly associated with anti-N or anti-S prevalence., Conclusions: SARS-CoV-2 seroprevalence increased over time among current and former PWID, suggesting cumulative increases in the incidence of SARS-CoV-2 infection and vaccination; however, there were disparities in infection-induced seroprevalence and infection and/or vaccine-induced seroprevalence within this study sample. Dedicated prevention and vaccination programs are needed to prevent disparities in infection and gaps in population immunity among PWID during emerging epidemics., Competing Interests: No conflict declared., (© 2023 The Authors. Published by Elsevier B.V.)

Background: Medication for opioid use disorder (MOUD) is an effective intervention to combat opioid use disorder and overdose, yet there is limited understanding of engagement in treatment over time in the community, contextualized by ongoing substance use. We aimed to identify concurrent trajectories of methadone prescriptions, buprenorphine prescriptions, and illicit opioid use among older adults with a history of injection drug use., Methods: We used data on 887 participants from the AIDS Linked to the IntraVenous Experience cohort, who were engaged in the study in 2013 and attended ≥1 visit during follow-up (2014-2019). Outcomes were self-reported MOUD prescription and illicit opioid use in the last 6 months. To identify concurrent trajectories in all 3 outcomes, we used group-based multi-trajectory modeling. We examined participant characteristics, including sociodemographics, HIV status, and other substance use, overall and by cluster., Results: We identified 4 trajectory clusters: (1) no MOUD and no illicit opioid use (43%); (2) buprenorphine and some illicit opioid use (11%); (3) methadone and no illicit opioid use (28%); and (4) some methadone and illicit opioid use (18%). While prevalence of each outcome was stable across time, transitions on/off treatment or on/off illicit opioid use occurred, with the rate of transition varying by cluster. The rate of transition was highest in Cluster 3 (0.74/person-year) and lowest in Cluster 1 (0.18/person-year). We saw differences in participant characteristics by cluster, including that the buprenorphine cluster had the highest proportion of people with HIV and participants who identified as non-Hispanic Black., Conclusions: Most participants had discontinued illicit opioid use and were also not accessing MOUD. Trajectories defined by engagement with buprenorphine or methadone had distinct sociodemographic and behavioral characteristics, indicating that tailored interventions to expand access to both types of treatment are likely needed to reduce harms associated with untreated opioid use disorder., Competing Interests: Declarations of 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., (Copyright © 2023 Elsevier B.V. All rights reserved.)

HIV-1 remains a global health crisis 1 , highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa 2 , we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV 3 . We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log 10 -transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair 4 . Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1L associates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: We describe the prevalence of COVID-19 vaccine uptake, substance use, and other factors associated with vaccine hesitancy among participants from nine North American cohort studies following a diverse group of individuals at risk for or living with HIV., Methods: Between May 2021 and January 2022, participants completed a survey related to COVID-19 vaccination. Participants included those with and without substance use. Those responding as 'no' or 'undecided' to the question "Do you plan on getting the COVID-19 vaccine?" were categorized as vaccine hesitant. Differences between groups were evaluated using chi-square methods and multivariable log-binomial models were used to calculate prevalence ratios (PR) of COVID-19 vaccine hesitancy with separate models for each substance., Results: Among 1,696 participants, COVID-19 vaccination was deferred or declined by 16%. Vaccine hesitant participants were younger, with a greater proportion unstably housed (14.8% vs. 10.0%; p = 0.02), and not living with HIV (48.% vs. 36.6%; p <.01). Vaccine hesitant participants were also more likely to report cannabis (50.0% vs. 42.4%; p = 0.03), methamphetamine (14.0% vs. 8.2%; p <.01), or fentanyl use (5.5% vs. 2.8%; p = 0.03). Based on multivariable analyses methamphetamine or fentanyl use remained associated with COVID-19 vaccine hesitancy (Adjusted PR = 1.4; 95% CI 1.1-1.9 and Adjusted PR = 1.6; 95% CI 1.0-2.6, respectively)., Conclusion: As new COVID-19 vaccines and booster schedules become necessary, people who use drugs (PWUD) may remain vaccine hesitant. Strategies to engage hesitant populations such as PWUD will need to be tailored to include special types of outreach such as integration with substance use programs such as safe injection sites or recovery programs., Competing Interests: 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., (© 2023 The Authors.)

Background: HIV infection is associated with more rapid progression of some comorbidities. This study assessed the impact of HIV-infection on the presentation and outcome of HCC., Methods: HCC patients attending the Mulago National Referral Hospital in Uganda were enrolled into a natural history study of HCC between March 2015 and February 2019. Standardized methods were used to collect clinical, ultrasound and laboratory data at enrolment. HCC cases were confirmed and enrolled based on a combination of clinical, ultrasound, tumor marker and pathology data. Follow-up contact was made at one, three, six, and twelve months post-enrolment to determine vital status. Symptoms and signs at diagnosis and subsequent survival were compared by HIV status. Kaplan Meier curves were used to assess HCC survival., Results: Of 441 persons with HCC, 383 (87.0%) died within 12 months following HCC diagnosis. The median (IQR) survival was 42 (20, 106) days. HIV infection was present in 79 (18%) cases. After adjusting for baseline demographic and clinical characteristics, HIV infection was associated with increased mortality but only among those with severe HIV-associated immunosuppression (CD4 count < 200 cells per cubic milliliter), aHR (95% C) = 2.12 (1.23-3.53), p = 0.004, and not among PLWH with ≥ 200 CD4 cells per cubic milliliter, aHR (95% C) = 1.15 (0.82-1.60), p = 0.417., Conclusion: Among relatively young Ugandans, HCC is a devastating disease with rapid mortality that is especially rapid among people living with HIV(PLWH). HIV was associated with slightly higher mortality, notably among PLWH with lower CD4 cell counts. As a substantial majority of PLWH diagnosed with HCC were engaged in HIV care, further investigation should determine the effectiveness of incorporating screening and early identification of HCC among high-risk individuals into existing HIV care programs. Concurrent with growing access to curative localized treatment for HCC in sub-Saharan Africa, leveraging HIV care infrastructure affords opportunities for earlier HCC intervention., (© 2023. The Author(s).)

Background: There are limited data on whether modifiable social factors foster psychological resilience and mental well-being among people who use drugs following Big Events. We examined the temporal association of pre-pandemic perceived social support with psychological resilience and negative mental health symptoms during the COVID-19 pandemic among people with a history of injection drug use., Methods: Between June and September 2020, we conducted a telephone survey among 545 participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study: a community-based cohort of adults with a history of injection drug use. Leveraging data from study visits in 2018-early 2020, associations of pre-pandemic perceived social support with psychological resilience scores (range=1-5) and the probability of negative mental health symptoms during the pandemic were assessed using multivariable linear and modified Poisson regression models, respectively., Results: Participants' median age was 58 years, 38.2% were female, 83.3% identified as Black, and 30.3% were living with HIV. During the pandemic, 14.5% had low (<3) resilience scores, 36.1% experienced anxiety, and 35.8% reported increased loneliness. Compared to participants in the lowest tertile of pre-pandemic social support, participants in the highest tertile had higher mean resilience scores (β = 0.27 [95% CI = 0.12, 0.43]), a lower probability of anxiety (prevalence ratio [PR] = 0.71 [95% CI = 0.52, 0.96]), and a lower probability of increased loneliness (PR = 0.62 [95% CI = 0.45, 0.84])., Conclusions: Pre-pandemic perceived social support was associated with greater psychological resilience and generally better mental well-being during the pandemic. Interventions that improve social support may foster psychological resilience and protect the mental well-being of people who use drugs, especially during periods of social disruption., Competing Interests: Conflict of interest statement None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Liver cancer is a major cause of cancer mortality worldwide. Screening individuals at high risk, including those with cirrhosis and viral hepatitis, provides an avenue for improved survival, but current screening methods are inadequate. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome analyses to evaluate 724 individuals from the United States, the European Union, or Hong Kong with hepatocellular carcinoma (HCC) or who were at average or high-risk for HCC. Using a machine learning model that incorporated multifeature fragmentome data, the sensitivity for detecting cancer was 88% in an average-risk population at 98% specificity and 85% among high-risk individuals at 80% specificity. We validated these results in an independent population. cfDNA fragmentation changes reflected genomic and chromatin changes in liver cancer, including from transcription factor binding sites. These findings provide a biological basis for changes in cfDNA fragmentation in patients with liver cancer and provide an accessible approach for noninvasive cancer detection., Significance: There is a great need for accessible and sensitive screening approaches for HCC worldwide. We have developed an approach for examining genome-wide cfDNA fragmentation features to provide a high-performing and cost-effective approach for liver cancer detection. See related commentary Rolfo and Russo, p. 532. This article is highlighted in the In This Issue feature, p. 517., (©2022 The Authors; Published by the American Association for Cancer Research.)

Introduction: The evaluation of the patterns of liver injury, derived from liver chemistry panels, often may narrow on probable causes of the liver insult especially when coupled with clinical history, examination, and other diagnostic tests., Methods: Among people living with and without HIV and attending care, we used the R ratio to evaluate for liver injury patterns. Liver injury patterns were defined as cholestatic ( R < 2), mixed ( R = 2-5), and hepatocellular ( R > 5)., Results: Overall, the proportions of participants with cholestatic liver injury, mixed liver injury, and hepatocellular liver injury were 55%, 34%, and 4%, respectively, with similar distribution when stratified by HIV status. Alcohol use among participants without HIV was associated with all patterns of liver injury (cholestatic liver injury (OR = 4.9 CI (1.0-24.2); p = 0.054), mixed liver injury (OR = 5.3 CI (1.1-27.3); p = 0.043), and hepatocellular liver injury (OR = 13.2 CI (1.0-167.3); p = 0.046)). Increasing age was associated with cholestatic liver injury among participants with HIV (OR = 2.3 CI (1.0-5.3); p = 0.038). Despite a high hepatitis B prevalence among participants with HIV, there was no association with liver injury., Conclusions: Liver injury is prevalent among both people living with and without HIV in care, and cholestatic liver injury is the most common pattern. Alcohol is associated with all patterns of liver injury and increasing age associated with cholestatic liver injury among people living without HIV and people living with HIV, respectively., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Clara Wekesa et al.)

People living with (PLWH) and at risk for HIV and people who use drugs (PWUD) are at heightened risk for health consequences of COVID-19 because of compromised immunity and high comorbidities. We studied their use of COVID-19 testing during the first year of the COVID-19 pandemic. Eight NIDA funded cohorts across North America in the Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO) administered multiple waves of a COVID-19 survey. Respondents were at least 18 years of age, half PLWH, and many active substance users. Wave one of the COVID-19 survey was May-November, 2020 and wave two October 2020-April 2021. Associations of COVID-19 testing with demographics, socio-demographics, substance use, and HIV-status were assessed. Of the 3762 responses from 2331 individuals, half reported ever COVID-19 testing (49.1 %), with 4.3 % reporting a positive test (163/3762 surveys=4.3 %) and 41.5 % of people reporting current symptoms reported having been tested. In multivariable analysis adjusting for age, sex, and cohort type associations with COVID-19 testing included African American/Black identification compared to Caucasian/white (adjusted odds ratio (AOR)= 0.68; 95 % confidence interval (CI) 0.53, 0.88); being unemployed (AOR=0.61; 95 % CI 0.51, 0.73), and living with HIV (AOR=0.76; 95 % CI0.65, 0.90). Findings from these C3PNO COVID-19 modules suggests that in the first year of the pandemic COVID-19 testing was not broadly accessed by these marginalized populations including PLWH and those unemployed. Factors associated with not testing may also parallel those for vaccination and identify populations needing better access to COVID-19 prevention., Competing Interests: Conflict of Interest No conflict declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The COVID-19 pandemic has compounded the longstanding drug poisoning crisis in Canada and the United States (US). Research is needed to understand the contributions of COVID-19 and subsequent infection control measures. We sought to estimate the prevalence of and factors associated with nonfatal overdose among participants in nine prospective cohorts of people who use unregulated drugs (PWUD) in Canada and the US., Methods: Data were derived from nine cohorts of PWUD in urban centres in Canada (Vancouver, BC) and the US (Baltimore, MD; Miami, FL; Chicago, IL; Los Angeles, CA) between May, 2020 and April, 2021. Multivariable logistic regression was used to identify factors associated with nonfatal overdose among participants who used unregulated drugs in the past month., Results: Among 885 participants (including 253 females), 41 (4.6 %) experienced a non-fatal overdose in the past month, and 453 (51.2 %) reported being highly impacted day-to-day by the pandemic. In multivariable analyses, people who experienced a non-fatal overdose were more likely to be female (Adjusted Odds Ratio [AOR]=2.18;95 % Confidence Interval [CI]=1.10-4.30); unstably housed/homeless (AOR=2.16;95 % CI=1.11-4.26); engaged in medications for opioid use disorder (AOR=2.45;95 % CI=1.19-4.97); and highly impacted day-to-day (AOR=2.42;95 % CI=1.22-5.10)., Conclusion: Our findings may reflect characteristics of participants who experienced a compounding of vulnerabilities during the pandemic and thus are vulnerable to overdose, including women, those unstably housed/homeless, and those who perceived their daily lives were highly impacted by the pandemic. Multi-level interventions are needed to remediate the vulnerabilities and address the main driver of poisoning crisis., Competing Interests: Conflict of interest M-JM holds the Canopy Growth professorship in cannabis science at the University of British Columbia, a position established through arm’s length gifts to the university from Canopy Growth, a licensed producer of cannabis, and the Government of British Columbia’s Ministry of Mental Health and Addictions. He has no financial relationships with the cannabis industry. All authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: This study examines individual-level factors associated with avoiding two important health services for people who use drugs-medications for treatment of opioid use disorder and syringe service programs-during the first year of the COVID-19 pandemic., Methods: Data come from two subsamples of people who use drugs who were active participants in one of nine cohort studies in Vancouver, British Columbia; Baltimore, Maryland; Los Angeles, California; Chicago, Illinois; and Miami, Florida. Participants were interviewed remotely about COVID-19-associated disruptions to healthcare. We estimated the association of demographic, social, and health factors with each outcome using logistic regression among 702 participants (medication analysis) and 304 participants (syringe service analysis.) Analyses were repeated, stratified by city of residence, to examine geographic variation in risk., Results: There were large differences between cities in the prevalence of avoiding picking up medications for opioid use disorder, with almost no avoidance in Vancouver (3%) and nearly universal avoidance in Los Angeles, Chicago, and Miami (>90%). After accounting for between-city differences, no individual factors were associated with avoiding picking up medications. The only factor significantly associated with avoiding syringe service programs was higher levels of self-reported worry about COVID-19., Conclusion: During the first year of the COVID-19 pandemic, geographic differences in service and policy contexts likely influenced avoidance of health and harm reduction services by people who use drugs in the United States and Canada more than individual differences between people., Competing Interests: Conflicts of interest Dr. Milloy holds the Canopy Growth professorship in cannabis science at the University of British Columbia, a position established through arm’s length gifts to the university from Canopy Growth, a licensed producer of cannabis, and the Government of British Columbia’s Ministry of Mental Health and Addictions. He has no financial relationships with the cannabis industry., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Alcohol use during the COVID-19 pandemic increased. People living with HIV or at risk for HIV acquisition often have psycho-social and structural barriers or co-occurring substance use making them vulnerable to the adverse effects of alcohol. We describe factors associated with alcohol use during the COVID-19 pandemic in this group., Methods: From May 2020 to February 2021, 1984 people enrolled in 6 existing cohort studies completed surveys about alcohol and other drug use during the COVID-19 pandemic. We describe the past-month prevalence of no alcohol use, low-risk use, and hazardous use. We use multinomial regression to describe factors associated with low-risk or hazardous alcohol use relative to no alcohol use., Results: Forty-five percent of participants reported no alcohol use, 33% low-risk use, and 22% hazardous use in the past 30 days. Cannabis and stimulant use were associated with a higher prevalence of low-risk use relative to no use. Tobacco, stimulant, cannabis use and recent overdose were associated with a higher prevalence of hazardous use relative to no use. Substance use treatment and living with HIV were associated with a lower prevalence of low-risk or hazardous use relative to no use., Conclusions: Stimulant use was strongly associated with a higher prevalence of hazardous alcohol use while engagement in substance use treatment or living with HIV was associated with a lower prevalence. Ascertaining hazardous alcohol and other drug use, particularly stimulants, in clinical care could identify people at higher risk for adverse outcome and harm reduction counseling., Competing Interests: Conflict of interest The study authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In 2020, the first year of the COVID-19 pandemic, overdose deaths increased. However, no studies have characterized changes in mortality during the pandemic in a well-characterized cohort of people who use drugs in active follow-up at the time of pandemic onset., Design: We compared all-cause and cause-specific mortality in the first year of the pandemic (Mar-Dec 2020) to the five years preceding (Jan 2015-Feb 2020), among participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study: a community-recruited cohort of adults from Baltimore who have injected drugs. 3510 participants contributed 17,498 person-years [py] of follow-up time. Cause and dates of death were ascertained through the National Death Index. Comparisons were made for the full cohort and within subgroups with potentially differential levels of vulnerability., Results: All-cause mortality in 2020 was 39.6 per 1000 py, as compared to 37.2 per 1000 py pre- pandemic (Adjusted Incidence Rate Ratio = 1.09, 95%: confidence interval: 0.84-1.41). Increases were mostly attributable to chronic disease deaths; injury/poisoning deaths did not increase. No pre-post differences were statistically significant., Conclusion: In this exploratory analysis of an older cohort of urban-dwelling adults who have injected drugs, mortality changes during the first year of the pandemic differed from national trends and varied across potentially vulnerable subgroups. More research is needed to understand determinants of increased risk of mortality during the pandemic among subgroups of people who use drugs., Competing Interests: Declarations of 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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: People who inject drugs are a population who are often unengaged with health care services. The objective of this study was to characterize COVID-19 vaccine hesitancy and uptake in a community-based sample of people who inject drugs in Baltimore, Maryland., Methods: The ALIVE study (AIDS Linked to the IntraVenous Experience) in Baltimore is a community-based cohort study of people with a history of injection drug use. From March 2 through June 28, 2021, 346 ALIVE participants completed a survey on substance use, structural determinants of health, and COVID-19 vaccine hesitancy. The exposure of interest was COVID-19 vaccine hesitancy, and the primary outcome was vaccination status as of June 30, 2021. We extracted data on the dates of vaccination from electronic medical records linked to study participants., Results: The median age of the sample was 60 years; most participants were male (66%) and non-Hispanic Black (87%). Most (55%) trusted the COVID-19 vaccine, and 68% had received ≥1 dose. After age standardization, survey participants were more likely than the Maryland general population to be unvaccinated (prevalence ratio = 1.20; 95% CI, 0.97-1.49; P = .10). Participants who somewhat trusted or did not trust the COVID-19 vaccine had 6-fold higher odds of being unvaccinated than participants who trusted the vaccine (odds ratio = 6.30; 95% CI, 3.74-10.60)., Conclusion: Uptake of COVID-19 vaccine among people with a history of injection drug use was high. Attitudes and knowledge about vaccination were important predictors of vaccine uptake. Education and outreach efforts could be effective in reducing hesitancy and increasing vaccination in substance-using populations.