Characterizing multimorbidity in ALIVE: Comparing single and ensemble clustering methods.

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.

Baltimore oral epidemiology, disease effects, and HIV evaluation study (BEEHIVE) study protocol: a prospective cohort study.

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.

Drug Use-Related Discrimination in Healthcare Settings and Subsequent Emergency Department Utilization in a Prospective Cohort Study of People With a History of Injection Drug Use.

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.

Designing and Validating a Novel Method for Assessing Delay Discounting Associated With Health Behaviors: Ecological Momentary Assessment Study.

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.

Proteomic Signature of HIV-Associated Subclinical Left Atrial Remodeling and Incident Heart Failure.

Background: People living with HIV (PLWH) are at higher risk of heart failure (HF) and preceding subclinical cardiac abnormalities, including left atrial dilation, compared to people without HIV (PWOH). Hypothesized mechanisms include premature aging linked to chronic immune activation. We leveraged plasma proteomics to identify potential novel contributors to HIV-associated differences in indexed left atrial volume (LAVi) among PLWH and PWOH and externally validated identified proteomic signatures with incident HF among a cohort of older PWOH. Methods: We performed proteomics (Olink Explore 3072) on plasma obtained concurrently with cardiac magnetic resonance imaging among PLWH and PWOH in the United States. Proteins were analyzed individually and as agnostically defined clusters. Cross-sectional associations with HIV and LAVi were estimated using multivariable regression with robust variance. Among an independent general population cohort, we estimated associations between identified signatures and LAVi using linear regression and incident HF using Cox regression. Results: Among 352 participants (age 55±6 years; 25% female), 61% were PLWH (88% on ART; 73% with undetectable HIV RNA) and mean LAVi was 29±9 mL/m 2 . Of 2594 analyzed proteins, 439 were associated with HIV serostatus, independent of demographics, hepatitis C virus infection, renal function, and substance use (FDR<0.05). We identified 73 of these proteins as candidate contributors to the independent association between positive HIV serostatus and higher LAVi, enriched in tumor necrosis factor (TNF) signaling and immune checkpoint proteins regulating T cell, B cell, and NK cell activation. We identified one protein cluster associated with LAVi and HIV regardless of HIV viral suppression status, which comprised 42 proteins enriched in TNF signaling, ephrin signaling, and extracellular matrix (ECM) organization. This protein cluster and 30 of 73 individual proteins were associated with incident HF among 2273 older PWOH (age 68±9 years; 52% female; 8.5±1.4 years of follow-up). Conclusion: Proteomic signatures that may contribute to HIV-associated LA remodeling were enriched in immune checkpoint proteins, cytokine signaling, and ECM organization. These signatures were also associated with incident HF among older PWOH, suggesting specific markers of chronic immune activation, systemic inflammation, and fibrosis may identify shared pathways in HIV and aging that contribute to risk of HF.

Longitudinal patterns of use of stimulants and opioids in the AIDS linked to the IntraVenous experience cohort, 2005-2019.

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.

Effectiveness of mRNA Booster Vaccine Against Coronavirus Disease 2019 Infection and Severe Outcomes Among Persons With and Without Immune Dysfunction: A Retrospective Cohort Study of National Electronic Medical Record Data in the United States.

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.

Impact of HLA class I functional divergence on HIV control.

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.

Estimation of place-based vulnerability scores for HIV viral non-suppression: an application leveraging data from a cohort of people with histories of using drugs.

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.

The forecasted prevalence of comorbidities and multimorbidity in people with HIV in the United States through the year 2030: A modeling study.

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.

Evaluation of Calibration Approaches for Indoor Deployments of PurpleAir Monitors.

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/m3) and 330 µg/m3. 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/m3 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/m3 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/m3, likely because the majority of the data used to train these models were below this concentration.

Mitochondrial DNA copy number is associated with incident chronic kidney disease and proteinuria in the AIDS linked to the intravenous experience cohort.

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.

Time-to-completion of COVID-19 vaccination primary series varies by HIV viral load status among people who inject drugs in Baltimore, Maryland.

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.

Hepatitis B care cascade among people with HIV/HBV coinfection in the North American AIDS Cohort Collaboration on Research and Design, 2012-2016.

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.

Trends in self-reported non-fatal overdose and patterns of substance use before and during the COVID-19 pandemic in a prospective cohort of adults who have injected drugs - Baltimore, Maryland, 2014-2022.

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.

Africa-specific human genetic variation near CHD1L associates with HIV-1 load.

HIV-1 remains a global health crisis1, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa2, 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 HIV3. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log10-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 repair4. 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.

Prevalence and correlates of SARS-CoV-2 seropositivity among people who inject drugs in Baltimore, Maryland.

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.

Substance use and other factors associated with COVID-19 vaccine uptake among people at risk for or living with HIV: Findings from the C3PNO consortium.

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.

Context and correlates of providing assistance with someone's first injection in the AIDS linked to the IntraVenous Experience cohort, Baltimore, MD.

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.