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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.)

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:  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 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.)

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: 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.

Background and Aims: During the past decades, people who inject drugs (PWID) have been impacted by the development of combination antiretroviral therapy (cART) to combat HIV/AIDS, the prescription opioid crisis and increased use of lethal synthetic opioids. We measured how these dynamics have impacted mortality among PWID in an urban US city., Design: Prospective cohort study using data from the AIDS Linked to the Intravenous Experience (ALIVE)., Setting: Baltimore, MD, USA from 1988 to 2018., Participants: A total of 5506 adult PWIDs (median age at baseline 37 years)., Measurements: Mortality was identified by linkage to National Death Index-Plus (NDI-Plus) and categorized into HIV/infectious disease (HIV/ID) deaths, overdose and violence-related (drug-related) deaths and chronic disease deaths. Person-time at risk accrued from baseline and ended at the earliest of death or study period. All-cause and cause-specific mortality were calculated annually. The Fine & Gray method was used to estimate the subdistribution hazards of cause-specific deaths accounting for competing risks., Findings: Among 5506 participants with 84 226 person-years of follow-up, 43.9% were deceased by 2018. Among all deaths, 30.5% were HIV/ID deaths, 24.4% drug-related deaths and 33.3% chronic disease deaths. Age-standardized all-cause mortality increased from 23 to 45 per 1000 person-years from 1988 to 1996, declined from 1996 to 2014, then trended upward to 2018. HIV/ID deaths peaked in 1996 coincident with the availability of cART, then continuously declined. Chronic disease deaths increased continuously as the cohort aged. Drug-related deaths declined until 2011, but increased more than fourfold by 2018. HIV/HCV infection and active injecting were independently associated with HIV/ID and drug-related deaths. Female and black participants had a higher risk of dying from HIV/ID deaths and a lower risk of dying from drug-related deaths than male and non-black participants., Conclusions: Deaths in Baltimore, MD, USA attributable to HIV/ID appear to have declined following the widespread use of combination antiretroviral therapy. Increases in the rates of drug-related deaths in Baltimore were observed prior to and continue in conjunction with national mortality rates associated with the opiate crisis., (© 2021 Society for the Study of Addiction.)

Objective: The objective of this study was to examine trends in fatal and nonfatal overdose in a community-based sample of current and former people who inject drugs (PWID)., Methods: Data from 4826 current and former PWID from the AIDS Linked to the IntraVenous Experience (ALIVE) observational cohort study in Baltimore, Maryland, were used to characterize fatal and nonfatal overdose rates from 1998 to 2019. Poisson regression was used to examine factors associated with nonfatal overdose and differences by race among 1052 PWID between 2014 and 2019., Results: Fatal overdose rates reached a high of 13 per 1000 person-years in 2018. Among 1052 current and former PWID, of whom 75% were Black and one-third were female, the nonfatal overdose rate of 529 per 1000 person-years in 2019 was 8 times higher than 2014 (incidence rate ratio [IRR]=7.76, 95% CI: 3.35, 18.0). The annual adjusted increase in nonfatal overdose rate was 53% among Black PWID (IRR=1.53, 95% CI: 1.34, 1.75), compared to 14% among White PWID (IRR=1.14, 95% CI: 0.88, 1.46). Urban residence, opioid use, depressive symptoms, and hepatitis C infection were positively associated with nonfatal overdose among Black PWID. Recent injection drug use and tranquilizer use was associated with increased overdose among Black and White PWID., Conclusions: Rates of fatal and nonfatal overdose were high and increased from 2014 to 2019 among current and former PWID, with the most dramatic increases in nonfatal overdose observed among Black PWID. These findings highlight the urgent need for additional resources to reduce the differential harms associated with opioids by race., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: There is limited data on the health and social consequences of the COVID-19 pandemic among people who inject drugs (PWID)., Methods: We conducted a rapid telephone survey from April-June 2020 among participants of the community-based AIDS Linked to the IntraVenous Experience (ALIVE) cohort study in Baltimore, Maryland. This interviewer-administered survey collected information on COVID-19 knowledge, symptoms, testing, diagnosis, and prevention behaviors, recent substance use, housing conditions, interruptions to healthcare, access to harm reduction and drug treatment, mental health, and social support., Results: Of 443 current and former PWID who participated in the survey, 36 % were female, 85 % were Black, 33 % were living with HIV and 50 % reported any substance use in the prior six months. COVID-19 awareness was high, but knowledge of symptoms and routes of transmission were lower. PWID reporting recent substance use were less likely to always socially distance (63 % vs. 74 % among those without recent use, p = 0.02), and Black PWID were more likely than non-Black to socially distance (73 % vs. 48 %, p < 0.0001) and use when alone (68 % vs.35 %, p < 0.01). Only 6% reported difficulty accessing healthcare, yet only 48 % of those on opioid-agonist treatment had a four-week supply available. While 34 % reported increased depressive symptoms, participants reported high levels of social support., Conclusions: This rapid assessment highlighted that PWID currently using drugs may be less able to practice social distancing and increased SARS-CoV-2 transmission may occur. Ongoing monitoring of substance use and mental health, as well as overdose prevention is necessary as the pandemic and public health responses continue., (Copyright © 2021. Published by Elsevier B.V.)

Background: The availability of effective, oral direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment has put elimination of HCV as a public health challenge within reach. However, little is known about the characteristics of transmission networks of people who inject drugs (PWID)., Methods: Sequencing of a segment of the HCV genome was performed on samples collected from a community-based cohort of PWID between August 2005 and December 2016. Phylogenetic trees were inferred, and clusters were identified (70% bootstrap threshold; 0.04 maximum genetic distance threshold). We describe sex, race, age difference, and HIV infection status of potential transmission partners. Logistic regression was used to assess factors associated with being in an HCV cluster., Results: Of 508 HCV genotype 1 viremic PWID, 8% (n = 41) were grouped into 20 clusters, consisting of 19 pairs and 1 triad. In adjusted analyses, female sex (odds ratio [OR] 2.3 [95% confidence interval (CI) 1.2-4.5]) and HIV infection (OR 5.7 [CI 2.7-11.9]) remained independently associated with being in an HCV infection cluster., Conclusions: Molecular epidemiological analysis reveals that, in this cohort of PWID in Baltimore, HIV infection and female sex were associated with HCV clustering. Combination HCV prevention interventions targeting HIV infected PWID and addressing HCV infection prevention needs of women have potential to advance HCV elimination efforts.

Introduction: We performed a cross-sectional study of HIV-uninfected men and women who inject drugs from the ALIVE cohort to examine if black men and women who inject drugs have higher levels of CD4+ T cells expressing the integrin heterodimer α4β7 compared to white men and women., Materials and Methods: Flow cytometry was used to examine expression of α4β7 and other markers associated with different functional CD4+ T cell subsets in both men and women who inject drugs., Results: Higher levels of α4β7, CCR5, and CCR6 were observed on CD4+ T cells from black participants compared with white participants. In a multivariable model, α4β7 expression differed by race, but not sex, age, or other factors., Discussion: Black men and women express higher percentages of α4β7 expressing CD4+ T cells, which may play a role in HIV disease., Competing Interests: SM has received speaker fees from Gilead Sciences that was not related to this work. The authors have no other conflicts of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: Overdose is a leading cause of death in the United States, especially among people who inject drugs (PWID). Improving naloxone access and carrying among PWID may offset recent increases in overdose mortality associated with the influx of synthetic opioids in the drug market. This study characterized prevalence and correlates of several naloxone outcomes among PWID., Methods: During 2018, a survey to assess experience with naloxone was administered to 915 participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study, an ongoing community-based observational cohort of people who currently inject or formerly injected drugs in Baltimore, Maryland. We examined the associations of naloxone outcomes (training, supply, use, and regular possession) with socio-demographic, substance use and healthcare utilization factors among PWID in order to characterize gaps in naloxone implementation among this high-risk population., Results: Median age was 56 years, 34% were female, 85% were African American, and 31% recently injected. In the past six months, 46% (n = 421) reported receiving training in overdose prevention, 38% (n = 346) had received a supply of naloxone, 9% (n = 85) had administered naloxone, and 9% (n = 82) reported usually carrying a supply of naloxone. Recent non-fatal overdose was not associated with any naloxone outcomes in adjusted analysis. Active opioid use (aOR = 2.10, 95% CI: 1.03, 4.28) and recent treatment of alcohol or substance use disorder (aOR = 2.01, 95% CI: 1.13, 3.56) were associated with regularly carrying naloxone., Conclusion: Further work is needed to encourage PWID to carry and effectively use naloxone to decrease rates of fatal opioid overdose. While accessing treatment for substance use disorder was positively associated with carrying naloxone, EMS response to 911 calls for overdose, the emergency department, and syringe services programs may be settings in which naloxone access and carrying could be encouraged among PWID., Competing Interests: The authors have declared that no competing interests exist.

Background: Multiple factors influence the human immunodeficiency virus (HIV) antibody response produced during natural infection, leading to responses that can vary in specificity, strength, and breadth., Methods: People who inject drugs identified as recently infected with HIV (n = 23) were analyzed for clustering of their viral sequences (genetic distance, <2%). Longitudinal antibody responses were identified for neutralizing antibody (Nab) potential, and differences in antibody subclass, specificity, and Fc receptor ligation using pseudovirus entry and multiplexed Fc array assays, respectively. Responses were analyzed for differences between subject groups, defined by similarity in the sequence of the infecting virus., Results: Viral sequences from infected individuals were grouped into 3 distinct clusters with 7 unclustered individuals. Subjects in cluster 1 generally had lower antibody response magnitudes, except for antibodies targeting the V1/V2 region. Subjects in clusters 2 and 3 typically had higher antibody response magnitudes, with the Fv specificity of cluster 2 favoring gp140 recognition. NAb responses differed significantly between clusters for 3 of 18 pseudoviruses examined (P < .05), but there were no differences in overall NAb breadth (P = .62)., Discussion: These data demonstrate that individuals infected with similar viral strains can generate partially similar antibody responses, but these do not drastically differ from those in individuals infected with relatively unrelated strains., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

This study examines correlates of hepatitis C virus (HCV) genetic clustering among community-recruited people who inject drugs enrolled in the AIDS Linked to the IntraVenous Experience cohort in Baltimore between 1988 and 1989. HCV RNA was extracted and the core/envelope-1 region was sequenced. Clusters were identified from maximum likelihood trees with 1000 bootstrap replicates using a 70% aLRT and a 4% genetic-distance threshold in Cluster Picker. Overall, 46% of participants were in a cluster, including 122 genotype-1a and 36 genotype-1b clusters with an average of 2-3 genetically linked HCV infections. The largest cluster consists of 9 participants. In univariable analysis, black race (PR = 1.66 [95% CI: 1.12-2.45]), age <35 years (PR = 1.18 [95% CI: 1.02-1.37]), and injection drug use of cocaine alone (PR = 1.30 [95% CI: 1.02-1.65]) were significantly associated with being in a cluster. Conversely, a history of medication-associated treatment (MAT) was negatively associated with being in a cluster (PR = 0.82 [95% CI: 0.71-0.95]). In multivariable analysis, black race (APR = 1.62 [95% CI: 1.11-2.38]) remained independently associated being in a cluster while MAT (APR = 0.85 [95% CI: 0.74-0.99]) remained negatively associated with clustering. Our findings suggest strong locally-propagated transmission networks during the early epidemic that was driven by younger PWID. In light of the current opioid epidemic in the US, these findings suggest an urgent need for preventive interventions to mitigate the growth of large HCV transmission networks., (Published by Elsevier B.V.)

People who inject drugs (PWID) face disparities in human immunodeficiency virus (HIV) treatment outcomes and may be less likely to achieve durable viral suppression. We characterized transitions into and out of viral suppression from 1997 to 2017 in a long-standing community-based cohort study of PWID, the AIDS Link to Intravenous Experience (ALIVE) Study, analyzing HIV-positive participants who had made a study visit in or after 1997. We defined the probabilities of transitioning between 4 states: 1) suppressed, 2) detectable, 3) lost to follow-up, and 4) deceased. We used multinomial logistic regression analysis to examine factors associated with transition probabilities, with a focus on transitions from suppression to other states. Among 1,061 participants, the median age was 44 years, 32% were female, 93% were African-American, 59% had recently injected drugs, and 28% were virologically suppressed at baseline. Significant improvements in durable viral suppression were observed over time; however, death rates remained relatively stable. In adjusted analysis, injection drug use and homelessness were associated with increased virological rebound in earlier time periods, while only age and race were associated with virological rebound in 2012-2017. Opioid use was associated with an increased risk of death following suppression in 2012-2017. Despite significant improvements in durable viral suppression, subgroups of PWID may need additional efforts to maintain viral suppression and prevent premature mortality., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019.)

Background: Fentanyl-related mortality continues to increase in the US, but knowledge of the drivers of fentanyl use (both intentional and unintentional) remains limited. We conducted a rapid assessment to characterize knowledge, attitudes and practices related to fentanyl use in a community-based cohort of current and former people who inject drugs (PWID) in Baltimore, Maryland., Methods: Between November 2017 and June 2018, participants of the AIDS Linked to the IntraVenous Experience (ALIVE) cohort completed a survey related to fentanyl use. Correlates of recent (past 6 months) fentanyl use and preference for fentanyl-contaminated and -substituted heroin (FASH) were examined using logistic regression among persons who reported using drugs in the prior six months., Results: Of 994 participants, 28% reported ever having used fentanyl, with 58% of those reporting recent use. Independent correlates of recent fentanyl use among the subset of participants reporting recent (past 6 month) drug use were younger age, male sex, homelessness, opioid use, cocaine use, and daily injection (p < 0.05 for all). 18% of those who recently used fentanyl reported preference for FASH, which was associated with younger age, homelessness and daily injection (p < 0.05 for all)., Conclusions: Recent fentanyl use was commonly reported. Interventions to reduce the harms associated with fentanyl use should target young, homeless PWID who may be more likely to seek out fentanyl., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Mental health care may mitigate negative consequences related to substance use and bolster engagement in care for drug dependence. Despite the increased risk of depression among people who inject drugs (PWID), the longitudinal relationship of depression symptoms with depression and drug treatment utilization in this population remains uncharacterized., Methods: Data on depressive symptoms and depression treatment from current and former PWID in the ALIVE (AIDS Linked to the IntraVenous Experience) community-based cohort who had ≥3 study visits from July 2005 to June 2016 were included. We used logistic regression analysis with generalized estimating equations to examine factors associated with depression treatment in the 12 months following reported major depressive symptoms (CES-D ≥ 23) in the absence of treatment. We further examined the association between depression, depression treatment, and subsequent engagement in drug treatment among those with active substance use or alcohol dependence., Results: Of the 1544 participants, 34% were female, the median age was 51 years, and 91% were African-American. PWID reported major depressive symptoms at 22% of study visits. In adjusted analysis, acute emergency care, suicidal ideation, and recent alcohol or drug treatment were positively associated with initiating depression treatment. Depression was positively associated with subsequent treatment for substance dependence among those actively using (aOR = 1.30, 95% CI: 1.10-1.53)., Conclusions: PWID experience a high burden of depressive symptoms with significant unmet need of treatment for depression. Our findings suggest that mental health providers should bolster connections to chronic disease and alcohol and drug treatment providers., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Increasing overdose mortality and new HIV outbreaks in the U.S. highlight the need to identify risk behavior profiles among people who inject drugs (PWID). We characterized latent classes of drug use among a community-based sample of 671 PWID in Baltimore during 2017 and evaluated associations of these classes with sharing syringes, obtaining syringes from pharmacies or syringe services programs (SSPs), and nonfatal overdose in the past 6 months. We identified three classes of current drug use: infrequent use (76% of participants), prescription drug use (12%), and heroin and/or cocaine injection (12%). PWID in the heroin and/or cocaine injection and prescription drug use classes had higher odds of both overdose and sharing syringes (relative to infrequent use). PWID in the prescription drug use class were 64% less likely to obtain syringes through SSPs/pharmacies relative to heroin and/or cocaine injection. Harm reduction programs need to engage people who obtain prescription drugs illicitly.

Introduction: Prescription drug abuse is a major public health problem in rural and suburban areas of the United States, however its emergence in large urban settings with endemic injection drug use remains understudied. We examined temporal trends in injection drug use initiation and mortality among people who inject drugs (PWID) in Baltimore, Maryland., Methods: Data were derived from the baseline assessment of PWID enrolled in a community-based cohort study with longitudinal follow-up for mortality assessment. PWID were recruited from 2005-2008 (N = 1,008) and 2015-2018 (N = 737). We compared characteristics by birth cohort (before/after 1980) and type of drug initiated (prescription opioids, prescription non-opioids, non-injection illicit drugs, or injection drugs). We calculated standardized mortality ratios (SMR) using the US general population as the reference., Results: PWID born after 1980 were more likely to initiate drug use with prescription opioids and non-opioids and had higher levels of polysubstance prior to injection initiation, compared to individuals born before 1980. Overall mortality was high: 2.59 per 100 person-years (95% CI: 2.27-2.95 per 100 person-years). Compared to the US population, the highest SMRs were observed among participants between 40-44 years of age, with especially high mortality among women in this age group (SMR:29.89, 95% CI: 15.24-44.54)., Conclusions: Mirroring national trends, the profile of PWID in Baltimore has changed with increased prescription drug abuse and high levels of polysubstance use among younger PWID. Interventions need to reach those using prescription drugs early after initiation of use in order to reduce transition to injecting. Urgent attention is warranted to address premature mortality, particularly among middle-aged and female PWID., Competing Interests: The authors have declared that no competing interests exist.

Background: Prescription drug misuse and its consequences (e.g., overdose) are a major public health concern. While national focus has been on opioids, misuse of sedatives/tranquilizers also occurs. Here we describe the use, correlates, and sources of prescription drugs in a community-based cohort of people who inject drugs (PWID)., Methods: We included participants of the AIDS Linked to the IntraVenous Experience (ALIVE) study in follow-up in 2014. We defined prescription drug use as use of opioids or sedatives/tranquilizers considering both medical "prescribed by a doctor" and non-medical sources "obtained from the street/friend/relative." Correlates were evaluated separately for opioids and sedatives/tranquilizers using logistic regression and included socioeconomic factors, health conditions, substance use, and health care access., Results: 823 predominantly African-American (90.6%) and male (66.3%) ALIVE participants with a median age of 55 were included. Prevalence of prescription opioid and sedative/tranquilizer use was 25.3% and 16.3% respectively. While the majority (70%) obtained prescription drugs exclusively through medical sources, the 30% who reported any non-medical source were also more likely to use other substances by injection and non-injection routes. PWID reporting prescription drug use (from medical and non-medical sources) were significantly more likely to report other substance use, mental health disorder, and recent contact with health care providers or detoxification facilities., Conclusions: Prescription drug use was highly prevalent among PWID. While it is difficult to distinguish medically indicated from non-medical use, high levels of prescription drug use in conjunction with other drugs and alcohol heightens the risk for drug overdose and other adverse consequences., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Chronic inflammation marked by elevated interleukin (IL)-6, soluble tumor necrosis factor (TNF)-α receptor (sTNFR)-1, and sTNFR-2 levels may play a detrimental role in aging and HIV infection. This study aimed to evaluate the relationships of circulating IL-6 with sTNFR-1 and sTNFR-2 levels in an aging cohort of injection drug users (IDUs) with or at high risk for HIV infection. The AIDS Linked to the Intravenous Experience (ALIVE) study is a community-recruited, prospective observational study of former and current IDUs in Baltimore, Maryland. Serum IL-6, sTNFR-1, and sTNFR-2 levels were measured using standard ELISA. Multivariate linear regression analysis was employed, adjusting for age, sex, HIV status, injection drug use, comorbidities, as well as HIV viral load, CD4 T cell counts, and antiretroviral therapy where appropriate. The analysis included 1,178 participants (316 HIV positive and 862 HIV negative). In the adjusted model, sTNFR-1 and sTNFR-2 were individually associated with IL-6 (regression coefficient: 0.877 and 0.556, respectively, for all participants; 0.607 and 0.407 for HIV positives; and 0.999 and 0.628 for HIV negatives, all p < 0.0001). In the model combining sTNFR-1 and sTNFR-2, the associations for sTNFR-1 remained significant (0.693 for all participants, p < 0.0001; 0.417 for HIV positives, p < 0.05; and 0.840 for HIV negatives), while those for sTNFR-2 were no longer significant. sTNFR-1 and sTNFR-2 were positively associated with IL-6 in ALIVE participants. These findings provide initial insight into the in vivo relationship between TNF-α activation and IL-6 and a basis for further investigations into potential mechanisms underlying chronic inflammation in aging and HIV infection.

Aims: To understand the environmental and contextual influences of illicit cocaine and heroin use and craving using mobile health (mHealth) methods., Design: Interactive mHealth methods of ecological momentary assessment (EMA) were utilized in the Exposure Assessment in Current Time (EXACT) study to assess drug use and craving among urban drug users in real time. Participants were provided with mobile devices and asked to self-report every time they either craved (without using) or used heroin or cocaine for 30 days from November 2008 through May 2013., Setting: Baltimore, MD, USA., Participants: A total of 109 participants from the AIDS Linked to the IntraVenous Experience (ALIVE) study., Measurements: For each drug use or craving event, participants answered questions concerning their drug use, current mood and their social, physical and activity environments. Odds ratios (OR) of drug use versus craving were obtained from logistic regression models with generalized estimating equations of all reported events., Findings: Participants were a median of 48.5 years old, 90% African American, 52% male and 59% HIV-infected. Participants were significantly more likely to report use rather than craving drugs if they were with someone who was using drugs [adjusted odds ratio (aOR) = 1.45, 95% confidence interval (CI) = 1.13, 1.86), in an abandoned space (aOR = 6.65, 95% CI = 1.78, 24.84) or walking/wandering (aOR = 1.68, 95% CI = 1.11, 2.54). Craving drugs was associated with being with a child (aOR = 0.26, 95% CI = 0.12, 0.59), eating (aOR = 0.54, 95% CI = 0.34, 0.85) or being at the doctor's office (aOR = 0.31, 95% CI = 0.12, 0.80)., Conclusions: There are distinct drug using and craving environments among urban drug users, which may provide a framework for developing real-time context-sensitive interventions., (© 2014 Society for the Study of Addiction.)

Objective: To evaluate whether HIV infection was associated with reduced physical performance, and to examine if reduced physical performance predicted mortality in our aging cohort of HIV-infected and HIV-uninfected persons., Design: Prospective, observational cohort of current and former injection drug users in the AIDS Linked to the IntraVenous Experience study in Baltimore, Maryland, USA., Methods: The Short Physical Performance Battery (SPPB) was used as an objective measure of physical performance and measured semiannually along with behavioral and demographic data. Correlates of reduced physical performance (SPPB score ≤10) were identified and the relationship between reduced physical performance, HIV infection and mortality was analyzed by Cox regression., Results: Among 12 270 person-visits contributed by 1627 participants, the median age was 51, 30.3% were HIV-infected and 32.6% had an SPPB score 10 or less. In multivariable models, HIV infection was independently associated with 30% increased odds of reduced physical performance [odds ratio 1.30; 95% confidence interval (CI):1.12-1.52]. Reduced physical performance predicted mortality in a dose-response manner and within all HIV disease strata. Whereas reduced physical performance alone (hazard ratio 2.52, 95% CI: 1.59-4.00) and HIV infection alone (hazard ratio 2.78, 95% CI: 1.70-4.54) increased mortality, HIV-infected participants with reduced physical performance had a six-fold increased mortality risk (hazard ratio 6.03, 95% CI: 3.80-10.0) compared with HIV-uninfected participants with higher physical performance., Conclusion: HIV infection was independently associated with reduced physical performance. HIV and reduced physical performance have independent and joint effects on mortality. Physical performance measurement may be an important research and clinical tool to predict adverse outcomes among aging HIV-infected persons.

This study utilized multilevel cross-classified models to longitudinally assess the association between neighborhood residential rehabilitation and injection drug use. We also assessed whether relocating between neighborhoods of varying levels of residential rehabilitation was associated with injection drug use. Residential rehabilitation was categorized into three groups (e.g. low, moderate, high), and lagged one visit to ensure temporality. After adjusting for neighborhood and individual-level factors, residence in a neighborhood with moderate residential rehabilitation was associated with a 23% reduction in injection drug use [AOR=0.77; 95% CI (0.67,0.87)]; residence in a neighborhood with high residential rehabilitation was associated with a 26% reduction in injection drug use [AOR=0.74; 95% CI (0.61,0.91)]. Continuous residence within neighborhoods with moderate/high rehabilitation, and relocating to neighborhoods with moderate/high rehabilitation, were associated with a lower likelihood of injection drug use. Additional studies are needed to understand the mechanisms behind these relationships., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Several epidemiological studies have suggested that hepatitis C virus (HCV) infection is associated with the presence of obstructive lung disease (OLD). However, there is a strong link between HCV infection and tobacco abuse, a major risk factor for the development of OLD. In this study we analyzed clinical, laboratory and spirometric data from 1068 study participants to assess whether HCV infection, viremia, or HCV-associated end organ damage were associated with OLD. Demographics, risk behavior, serologic status for HCV and HIV, and spirometric measurements were collected from a cross-sectional analysis of the Acquired Immunodeficiency Syndrome (AIDS) Linked to the IntraVenous Experience (ALIVE) study, an observational cohort of IDUs followed in Baltimore, MD since 1988. Of 1,068 participants, 890 (83%) were HCV positive and 174 (16%) met spirometric criteria for OLD. Factors independently associated with OLD were age and BMI. HCV infection, viral load and HCV-associated end organ damage were similar in participants with and without OLD. In summary, there was no independent association between markers of HCV exposure, chronicity, viremia, or HCV-associated end-organ damage with OLD. Our findings support the strong correlation between HCV status, injection drug use, and smoking. These data suggest that HCV may not be a sole contributor to the increased prevalence of OLD described in previous studies of HCV-infected individuals.

Objectives: There are few systematic assessments of street-obtained buprenorphine use from community-based samples in the United States. The objective of this study was to characterize the prevalence, correlates, and reasons for street-obtained buprenorphine use among current and former injection drug users (IDUs) in Baltimore, Maryland., Methods: In 2008, participants of the ALIVE (AIDS Linked to the IntraVenous Experience) study, a community-based cohort of IDUs, were administered a survey on buprenorphine. Street-obtained buprenorphine represented self-reported use of buprenorphine obtained from the street or a friend in the prior three months., Results: Six hundred and two respondents were predominantly male (65%), African-American (91%), and 30% were HIV-positive. Overall, nine percent reported recent street-obtained buprenorphine use, and only 2% reported using to get high. Among active opiate users, 23% reported recent use of street-obtained buprenorphine. Use of buprenorphine prescribed by a physician, injection and non-injection drug use, use of street-obtained methadone and prescription opiates, homelessness, and opioid withdrawal symptoms were positively associated, while methadone treatment, health insurance, outpatient care, and HIV-infection were negatively associated with recent street-obtained buprenorphine use in univariate analysis. After adjustment, active injection and heroin use were positively associated with street-obtained buprenorphine use. Ninety-one percent reported using street-obtained buprenorphine to manage withdrawal symptoms., Conclusions: While 9% reported recent street-obtained buprenorphine use, only a small minority reported using buprenorphine to get high, with the majority reporting use to manage withdrawal symptoms. There is limited evidence of diversion of buprenorphine in this sample and efforts to expand buprenorphine treatment should continue with further monitoring., (© 2013.)

Background: While urban redevelopment is intended to ameliorate urban decay, some studies demonstrate that it can negatively impact some residents. Few studies have considered its impact on persons with a history of drug use., Methods: A convenience sample of 25 current or former injection drug users from Baltimore, Maryland, enrolled in the AIDS Linked to the Intravenous Experience study, and reporting residence in or bordering a redeveloping neighborhood participated in 1-2 semi-structured in-depth interviews from July, 2011 to February, 2012. Interviews explored personal experiences with redevelopment and perceptions of community-wide impact. Data were analyzed using the constant comparison method., Results: Respondents rarely described urban redevelopment as solely negative or positive. Revitalization and increased security in the redeveloping area were reported as positive consequences. Negative consequences included the lack of redevelopment-related employment opportunities, disruption of social ties, and housing instability among relocated residents. Respondents also said that urban redevelopment led to the displacement of drug markets to adjacent neighborhoods and outlying counties. Residential relocation and displacement of drug markets were reported as beneficial for persons in contemplative and later stages of recovery., Conclusion: These findings support a holistic approach to urban redevelopment that increases access to employment opportunities and affordable housing, and ensures equitable coverage of public services such as law enforcement., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Few studies have assessed the temporal association between homelessness and injection drug use, and injection-related risk behavior., Methods: Among a cohort of 1405 current and former injection drug users in follow-up from 2005 to 2009, we used random intercept models to assess the temporal association between homelessness and subsequent injection drug use, and to determine whether the association between homelessness and sustained injection drug use among active injectors differed from the association between homelessness and relapse among those who stopped injecting. We also assessed the association between homelessness and subsequent injection-related risk behavior among participants who injected drugs consecutively across two visits. Homelessness was categorized by duration: none, <1 month, and ≥1 month., Results: Homelessness was reported on at least one occasion by 532 (38%) participants. The relationship between homelessness and subsequent injection drug use was different for active injectors and those who stopped injecting. Among those who stopped injecting, homelessness was associated with relapse [<1 month: AOR=1.67, 95% CI (1.01, 2.74); ≥1 month: AOR=1.34 95% CI (0.77, 2.33)]. Among active injectors, homelessness was not associated with sustained injection drug use [<1 month: AOR=1.03, 95% CI (0.71, 1.49); ≥1 month: AOR=0.81 95% CI (0.56, 1.17)]. Among those injecting drugs across two consecutive visits, homelessness ≥1 month was associated with subsequent injection-related risk behavior [AOR=1.61, 95% CI (1.06, 2.45)]., Conclusion: Homelessness appears to be associated with relapse and injection-related risk behavior. Strengthening policies and interventions that prevent homelessness may reduce injection drug use and injection-related risk behaviors., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate whether HAART is associated with subsequent sexual and drug-related risk behavior compensation among injection drug users (IDUs)., Design: A community-based cohort study of 362 HIV-infected IDUs initiating HAART in Baltimore, Maryland., Methods: HAART use and risk behavior was assessed at 8316 biannual study visits (median 23). Using logistic regression with generalized estimating equations (GEE), we examined the effect of HAART initiation on changes in risk behavior while adjusting for sociodemographics, alcohol use, CD4 cell count, year of initiation and consistency of HAART use., Results: At HAART initiation, participants were a median of 44.4 years old, 71.3% men and 95.3% African-American. In multivariable analysis, HAART initiation was associated with a 75% reduction in the likelihood of unprotected sex [adjusted odds ratio (aOR) 0.25; 95% confidence interval (CI), 0.19-0.32] despite no change in overall sexual activity (aOR 0.95; 0.80-1.12). Odds of any injecting decreased by 38% (aOR 0.62; 0.51-0.75) after HAART initiation. Among the subset of persistent injectors, needle-sharing increased nearly two-fold (aOR 1.99; 1.57-2.52). Behavioral changes were sustained for more than 5 years after HAART initiation and did not differ by consistency of HAART use. Reporting specific high-risk behaviors in the year prior to initiation was a robust predictor of engaging in those behaviors subsequent to HAART., Conclusion: Overall, substantial declines in sexual risk-taking and active injecting argue against significant behavioral compensation among IDUs following HAART initiation. These data also provide evidence to support identifying persons with risky pre-HAART behavior for targeted behavioral intervention.

Despite reports of increasing non-medical prescription drug use, relatively few studies have systematically evaluated the prevalence and correlates of non-medical prescription drug use, particularly in populations that might be especially vulnerable (e.g., injection drug users [IDUs]). We examined factors associated with non-medical prescription drug use among a community-based cohort of current and former IDUs in Baltimore (The ALIVE Study). We conducted a cross-sectional analysis of data from cohort participants that responded to a survey that included questions on non-medical prescription drug use between 2005-06 (n=1320). Non-medical prescription drug use was considered to be use of any of the following: Opiates (Oxycontin, Percocet), Benzodiazepines or Clonidine, purchased on the street and taken orally within the last six months. Data on other covariates of interest (e.g., demographics, substance use, general health) was obtained through a standardized interview. The median age was 46 years; 66% were male, 85% were African-American. Twenty one percent reported any non-medical prescription drug use; 12% reported using more than one drug. Non-medical use of opiates was most common (17%). In multivariate analysis, non-medical prescription drug use was significantly associated with Caucasian race (prevalence ratio [PR]: 1.79), self-reported bodily pain (PR: 1.58), hazardous alcohol use (PR: 1.47), marijuana use (PR: 1.65), non-injection cocaine/heroin use (PR: 1.70), diverted use of buprenorphine (PR: 1.51) or methadone (PR: 2.51), and active injection drug use (PR: 3.50; p<0.05 for all). The association between bodily pain and non-medical prescription drug use was stronger among persons that were not using substances (marijuana, injecting drugs, snorting/smoking heroin, cocaine, using crack) as compared to those using these substances. The high prevalence of non-medical prescription drug use among this population warrants further research and action. Information on the risks of nonmedical prescription drug use especially overdose, should be incorporated into interventions targeted at IDUs., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Incarceration may lead to interruptions in antiretroviral therapy (ART) for persons receiving treatment for human immunodeficiency virus (HIV) infection. We assessed whether incarceration and subsequent release were associated with virologic failure for injection drug users (IDUs) who were previously successfully treated with ART., Methods: ALIVE is a prospective, community-based cohort study of IDUs in Baltimore, Maryland. IDUs receiving ART during 1998-2009 who successfully achieved an HIV RNA level below the limit of detection (<400 copies/mL) were followed up for development of virologic failure at the subsequent semiannual study visit. Logistic regression with generalized estimating equations was used to assess whether incarceration was independently associated with virologic failure., Results: Of 437 HIV-infected IDUs who achieved undetectable HIV RNA for at least one study visit, 69% were male, 95% were African-American, and 40% reported at least one incarceration during follow-up. Virologic failure occurred at 26.3% of visits after a median of 6 months since achieving undetectable HIV RNA. In multivariate analysis accounting for demographic characteristics, drug use, and HIV disease stage, brief incarceration was strongly associated with virologic failure (adjusted odds ratio, 7.7; 95% confidence interval, 3.0-19.7), although incarceration lasting >30 days was not (odds ratio, 1.4; 95% confidence interval, .8-2.6)., Conclusions: Among IDUs achieving viral suppression while receiving ART, virologic failure occurred with high frequency and was strongly associated with brief incarceration. Efforts should be made to ensure continuity of care both during and after incarceration to improve treatment outcomes and prevent viral resistance in this vulnerable population.

The objective of this study was to identify longitudinal patterns of injection drug use over 20 years in the AIDS Linked to the Intravenous Experience (ALIVE) Study, a community-based cohort of injection drug users (IDUs) in Baltimore, Maryland, with a focus on injection cessation. Starting in 1988, persons over 18 years of age with a history of injection drug use were recruited into the study. Participants provided information on their injection drug use semiannually through 2008. The analysis was restricted to 1,716 IDUs with at least 8 study visits. Finite mixture models were used to identify trajectories and predictors of injection patterns over time. The mean age of participants was 35 years; 75% were male, and 95% were African-American. Five distinct patterns were identified: 2 usage patterns (32% engaged in persistent injection and 16% had frequent relapse) and 3 cessation patterns (early cessation (19%), delayed cessation (16%), and late cessation (18%)). A history of drug treatment, no recent use of multiple substances, and less frequent injection distinguished the early cessation group from the other groups. This study demonstrated multiple trajectories of drug injection behaviors, with a substantial proportion of IDUs stopping injection over extended time frames. For maximum effectiveness, public health programs for IDUs should be long-term, comprehensive, and targeted toward individual patterns of use.

Background: Population-level hepatitis C virus (HCV) infection incidence is a surrogate for community drug-related risk., Methods: We characterized trends in human immunodeficiency virus (HIV) and HCV infection incidence and HCV infection prevalence among injection drug users (IDUs) recruited over 4 periods: 1988-1989, 1994-1995, 1998, and 2005-2008. We calculated HIV and HCV infection incidence within the first year of follow-up among IDUs whose test results were negative for these viruses at baseline (n = 2061 and n = 373, respectively). We used Poisson regression to compare trends across groups., Results: HIV infection incidence declined significantly from 5.5 cases/100 person-years (py) in the 1988-1989 group to 2.0 cases/100 py in the 1994-1995 group to 0 cases/100 py in the 1998 and 2005-2008 groups. Concurrently, HCV infection incidence declined but remained robust (22.0 cases/100 py in the 1988-1989 cohort to 17.2 cases/100 py in the 1994-1995 cohort, 17.9 cases/100 py in the 1998 cohort, and 7.8 cases/100 py in the 2005-2008 cohort; P = .07). Likewise, HCV infection prevalence declined, but chiefly in younger IDUs. For persons aged <39 years, relative to the 1988-1989 cohort, all groups exhibited significant declines (adjusted prevalence ratio [PR] for the 2005-08 cohort, .73; 95% confidence interval [CI], .65-.81). However, for persons aged ≥ 39 years, only the 2005-2008 cohort exhibited declining prevalence compared with the 1988-1989 cohort (adjusted PR, .87; 95% CI, .77-.99)., Conclusions: Although efforts to reduce blood-borne infection incidence have had impact, this work will need to be intensified for the most transmissible viruses, such as HCV.

Objective: to estimate the effect of alcohol consumption on HIV acquisition while appropriately accounting for confounding by time-varying risk factors., Design: african-American injection drug users in the AIDS Link to Intravenous Experience cohort study. Participants were recruited and followed with semiannual visits in Baltimore, Maryland between 1988 and 2008., Methods: marginal structural models were used to estimate the effect of alcohol consumption on HIV acquisition., Results: at entry, 28% of 1525 participants were women with a median (quartiles) age of 37 (32-42) years and 10 (10-12) years of formal education. During follow-up, 155 participants acquired HIV and alcohol consumption was 24, 24, 26, 17, and 9% for 0, 1-5, 6-20, 21-50, and 51-140 drinks per week over the prior 2 years, respectively. In analyses accounting for sociodemographic factors, drug use, and sexual activity, hazard ratios for participants reporting 1-5, 6-20, 21-50, and 51-140 drinks per week in the prior 2 years compared to participants who reported 0 drinks per week were 1.09 (0.60-1.98), 1.18 (0.66-2.09), 1.66 (0.94-2.93), and 2.12 (1.15-3.90), respectively. A trend test indicated a dose-response relationship between alcohol consumption and HIV acquisition (P value for trend = 9.7 × 10)., Conclusion: a dose-response relationship between alcohol consumption and subsequent HIV acquisition is indicated, independent of measured known risk factors., (2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.)

Introduction: Urban U.S. populations are burdened by intersecting epidemics of HIV infection, injection drug use, and cigarette smoking. Given the substantial morbidity attributable to tobacco in these populations, we characterized smoking behaviors, nicotine addiction, and tobacco exposure among HIV-infected and HIV-uninfected injection drug users (IDUs) in Baltimore, Maryland., Methods: Smoking behaviors among participants in the ALIVE Study were assessed using interviewer-administered questionnaires. Smoking history and nicotine dependence (Fagerstrom Index scores) were compared by HIV and drug injecting status. Serum cotinine (a nicotine metabolite) was measured for a sample of participants by enzyme immunoassay., Results: Among 1052 participants (29.7% HIV-infected, 39.8% active injectors), 85.2% were current smokers and 9.3% were former smokers. Smoking prevalence, age at smoking initiation, and cumulative tobacco exposure were similar by HIV status. Median Fagerstrom scores of 4 for HIV-infected and HIV-uninfected smokers indicated moderate nicotine dependence. Daily cigarette consumption was identical by HIV status (median 10 cigarettes), although HIV-infected participants were less likely to smoke 1+ pack daily compared to HIV-uninfected participants (18.0% vs. 26.9%, p=0.001). Compared to former injectors, active injectors had higher smoking prevalence (90.5% vs. 81.7%, p=0.0001), greater daily cigarette consumption (30.7% vs. 19.6% smoked 1+ pack daily, p=0.0001), and slightly higher Fagerstrom scores (median 5 vs. 4). Cotinine levels paralleled self-reported cigarette consumption., Discussion: Tobacco use is extremely common among inner-city IDUs. Smoking behavior and nicotine dependence did not materially differ by HIV status but were associated with active drug injection. Cessation efforts should target the dual dependence of cigarettes and drugs experienced among this population., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Obstructive lung disease (OLD) is frequently unrecognized and undertreated. Urban drug users are at higher risk for OLD due to race, behavioral, and socioeconomic characteristics, yet little data exist on prevalence and risk factors associated with unrecognized OLD in this population., Objective: The objective of this study is to determine the prevalence of unrecognized OLD in an urban population and identify the characteristics associated with lack of physician-diagnosed OLD., Design: Cross-sectional analysis from the Acquired Immunodeficiency Syndrome Linked to the Intravenous Experience (ALIVE) study, an observational study of current and former injection drug users in Baltimore, Maryland, USA., Participants: All participants with spirometry-defined airflow obstruction were stratified by the presence or absence of physician diagnosis of OLD., Main Measures: Using cross-sectional demographic, clinical, and spirometric measurements, multivariable regression models were generated to identify factors independently associated with unrecognized OLD., Key Results: Of the 1083 participants evaluated in the ALIVE lung substudy, 176 (16.3%) met spirometric criteria for OLD. Of those, only 88 (50%) had a physician diagnosis of OLD. The prevalence of unrecognized OLD decreased as severity of airflow obstruction increased. Factors independently associated with unrecognized OLD were absence of respiratory symptoms (prevalence ratio [PR], 1.70; 95% confidence interval [CI]: 1.29-2.23; P < 0.01) and less severe dyspnea (PR, 0.83; 95% CI: 0.72-0.96, per point increase in dyspnea scale; P = 0.01). In the subset of human immunodeficiency virus (HIV)-infected participants, the use of antiretroviral therapy (ART) was independently associated with an increased prevalence of unrecognized OLD (PR, 1.93; 95% CI: 1.05-3.56; P = 0.03)., Conclusions: In a cohort of current and former urban drug users, OLD is substantially underrecognized and associated with lack of respiratory symptoms. Relying on the presence of respiratory symptoms as a trigger to perform spirometry may result in a substantial underdiagnosis of OLD in this population. HIV-infected individuals receiving ART are a population particularly vulnerable to unrecognized OLD.

Objectives: To examine the impact of HIV on lung cancer incidence and survival., Design: : Prospective study of 2495 HIV-infected and HIV-uninfected injection drug users in Baltimore, MD., Methods: Cancer data were obtained from the Maryland Cancer Registry. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer in 2 strata of packs of cigarettes smoked per day by HIV serostatus, and for mortality by HIV serostatus., Results: HIV-infected participants had twice the risk (HR = 2.3; 95% CI: 1.1 to 5.1) of lung cancer. There was no evidence of an interaction between HIV and packs of cigarettes smoked per day (P interaction = 0.18). Compared with participants who smoked <1.43 packs per day, among HIV-uninfected individuals lung cancer risk was 6 times greater (HR = 5.9; 95% CI: 2.1 to 17) and among HIV-infected individuals lung cancer risk was doubled (HR = 2.1; 95% CI: 0.63 to 6.8) in persons who smoked ≥1.43 per day. Additionally, HIV was associated with 4 times the risk of death (HR = 3.8; 95% CI: 0.92 to 15) in lung cancer cases., Conclusions: HIV was associated with increased risk of lung cancer, after adjusting for smoking. However, no evidence was observed for synergistic effects of HIV and smoking. Further, HIV was associated with poorer lung cancer survival after accounting for cancer stage.

Background and Objectives: Proteinuria is a major determinant of chronic kidney disease. We aimed to characterize the prevalence and correlates of proteinuria in a cohort of HIV-infected and uninfected injection drug users., Design, Setting, Participants, & Measurements: A cross-sectional analysis was performed among 902 injection drug users (273 HIV-infected) in the AIDS Linked to the Intravenous Experience cohort. The primary outcome was proteinuria defined as having a urine protein/creatinine concentration ratio >200 mg/g. Poisson regression with robust variance was used to determine prevalence ratios., Results: Overall, 24.8% of participants had proteinuria; the prevalence was 2.9 times higher among HIV-infected participants (45%) compared with HIV-uninfected participants (16%). In addition, age, health insurance, employment status, hepatitis B and C serostatus, diabetes, and high BP were associated with proteinuria. Neither antiretroviral therapy nor features of illicit drug use history were associated with proteinuria. In multivariate analysis, HIV infection, unemployment, increased age, diabetes, hepatitis C infection, and high BP were significantly associated with a higher prevalence of proteinuria., Conclusions: In an aging, predominantly African-American cohort of injection drug users, we found a striking burden of proteinuria that was strongly associated with HIV status. In addition to being a pathway to ESRD, proteinuria is a potent risk factor for cardiovascular morbidity and mortality. Evaluation of aggressive screening and disease-modification strategies in this high-risk population is warranted.

Background: Most hepatitis delta virus (HDV) prevalence estimates from the United States are >10 years old, and HDV has shown significant temporal variation in other populations. HDV-hepatitis B virus (HBV) dual infection progresses rapidly, has more complications, and has a different treatment regimen than HBV infection alone. Accurate estimates of prevalence and risk factors are important to help clinicians decide who to screen., Methods: Injection drug users in Baltimore, Maryland, who were positive for HBV serologic markers were tested for hepatitis delta antibody (HDAb) at 2 time periods: 1988-1989 (194 participants) and 2005-2006 (258 participants). Those who were HDAb positive in 2005-2006, plus a random sample of HDAb negative, HBV-positive participants were tested for HDV RNA, HBV DNA, and HCV RNA. Characteristics associated with HDV exposure and viremia were identified., Results: HDV prevalence declined from 15% in 1988-1989 to 11% in 2005-2006. Among those with chronic HBV infection, prevalence increased from 29% (14 of 48 participants) to 50% (19 of 38 participants) (P=.05). Visiting a "shooting gallery" (a location where people gather to inject illegal drugs) was a strong correlate of HDAb positivity (relative risk, 3.08; P=.01). Eight (32%) of those who were HDAb positive had HDV viremia. Viremic participants had elevated liver enzyme levels and more emergency room visits., Conclusions: The temporal increase in HDV prevalence among those with chronic HBV infection is troubling; understanding this change should be a priority to prevent the burden from increasing.

Background: We characterized temporal trends in highly active antiretroviral therapy (HAART) initiation (1996-2008) among treatment-eligible persons in a community-based cohort of current and former injection drug users (IDUs) in Baltimore, Maryland., Methods: The AIDS Linked to the IntraVenous Experience (ALIVE) cohort has been observing human immunodeficiency virus (HIV)-positive IDUs since 1988. HAART eligibility was defined as the first visit after 1 January 1996 at which the patient's CD4(+) cell count was <350 cells/microL. Temporal trends and predictors of HAART initiation were examined using chi(2) tests for trend and lognormal survival models., Results: The median age of 582 HAART-eligible IDUs was 41 years; 75% of the subjects were male, 97% were African American, and 60% were active IDUs. Of these 582 individuals, 345 initiated HAART over 1803 person-years (19.2 subjects per 100 person-years; 95% confidence interval, 17.2-21.3 subjects per 100 person-years); there was no statistically significant temporal trend in HAART initiation. Independent predictors of delayed initiation included heavy injection drug use; having a prior AIDS diagnosis, having a lower CD4(+) cell count, having a usual source of care, and having health insurance were predictors of more-rapid initiation. The delay between eligibility and initiation decreased among those who became eligible most recently (2003-2007), compared with those in earlier periods (1996-2002); however, a substantial number of patients who became eligible in recent years either initiated HAART after a substantial delay or did not initiate HAART at all., Conclusions: We failed to observe substantial improvement in HAART initiation among current and former IDUs over a 12-year period; heavy use of injection drugs remains the major barrier to HAART initiation and to consistent HIV care. The fact that many IDUs initiate HAART after a significant delay or do not initiate it at all raises concern that disparities in HIV care for IDUs remain at a time of simplified antiretroviral regimens and increasing adoption of earlier treatment.

Background: Injection drug use is associated with an increased risk of human immunodeficiency virus (HIV) infection and with obstructive lung diseases (OLD). Understanding how HIV and OLD may impact respiratory symptoms among injection drug users (IDUs) is important to adequately care for this high-risk population. We characterized the independent and joint effects of HIV and OLD on respiratory symptoms of a cohort of inner-city IDUs., Methods: Demographics, risk behavior and spirometric measurements were collected from a cross-sectional analysis of the Acquired Immunodeficiency Syndrome Link to the IntraVenous Experience study, an observational cohort of IDUs followed in Baltimore, MD since 1988. Participants completed a modified American Thoracic Society respiratory questionnaire and the Medical Research Council (MRC) dyspnea score to assess respiratory symptoms of cough, phlegm, wheezing and dyspnea., Results: Of 974 participants, 835 (86%) were current smokers and 288 (29.6%) were HIV-infected. The prevalence of OLD (FEV1/FVC < or = 0.70) was 15.5%, and did not differ by HIV status. OLD, but not HIV, was associated with increased frequency of reported respiratory symptoms. There was a combined effect of OLD and HIV on worsening of MRC scores. OLD and HIV were independently associated with an increased odds of reporting an MRC > or = 2 (OR 1.83 [95%CI 1.23-2.73] and 1.50 [95%CI 1.08-2.09], respectively). COPD, but not HIV, was independently associated with reporting an MRC >/= 3 (OR 2.25 [95%CI 1.43-3.54] and 1.29 [95%CI 0.87-1.91], respectively)., Conclusions: While HIV does not worsen cough, phlegm or wheezing, HIV significantly increases moderate but not severe dyspnea in individuals of similar OLD status. Incorporating the MRC score into routine evaluation of IDUs at risk for OLD and HIV provides better assessment than cough, phlegm and wheezing alone.

Background: We sought to identify factors associated with newly detected human papillomavirus (HPV) infection in a high-risk cohort of injection drug using women in Baltimore, MD., Methods: We studied 146 HIV-infected and 73 HIV-uninfected female participants in a 5-year prospective HIV natural history study. We examined the association of sexual and nonsexual risk factors and newly detected type-specific HPV infection as determined by consensus PCR between consecutive visits., Results: Newly detected HPV was more common among HIV-infected versus HIV-uninfected women (30% and 6%, respectively; P <0.01). Among the entire cohort, recent crack use (OR, 1.7; 95% CI, 1.1-2.6) and HIV infection/CD4 cell count were independent predictors for new HPV detection (HIV-uninfected as reference, OR, 4.6; 95% CI, 2.3-8.9, OR, 5.4; 95% CI, 2.8-10.3, and OR, 10.9; 95% CI, 5.5-21.7 for HIV-infected CD4 >500, 200-500, and <200, respectively). Among HIV-uninfected women, recent marijuana use was an independent predictor of newly detected HPV infection (OR, 3.5; 95% CI, 1.3-9.5)., Conclusions: Newly detected HPV clearly increased with greater immunosuppression in HIV-infected injection drug users. Larger studies of HIV-uninfected and infected high-risk individuals are needed to clarify the independent associations of crack and marijuana use with new (or reactivated) HPV infection.

We characterized hepatitis C virus (HCV) treatment knowledge, experience and barriers in a cohort of community-based injection drug users (IDUs) in Baltimore, MD. In 2005, a questionnaire on HCV treatment knowledge, experience and barriers was administered to HCV-infected IDUs. Self-reported treatment was confirmed from medical records. Of 597 participants, 71% were male, 95% African-American, 31% HIV co-infected and 94% were infected with HCV genotype 1; 70% were aware that treatment was available, but only 22% understood that HCV could be cured. Of 418 who had heard of treatment, 86 (21%) reported an evaluation by a provider that included a discussion of treatment of whom 30 refused treatment, 20 deferred and 36 reported initiating treatment (6% overall). The most common reasons for refusal were related to treatment-related perceptions and a low perceived need of treatment. Compared to those who had discussed treatment with their provider, those who had not were more likely to be injecting drugs, less likely to have health insurance, and less knowledgeable about treatment. Low HCV treatment effectiveness was observed in this IDU population. Comprehensive integrated care strategies that incorporate education, case-management and peer support are needed to improve care and treatment of HCV-infected IDUs.

Background: African Americans with human immunodeficiency virus type 1 (HIV-1) infection and kidney disease are at increased risk of end-stage renal disease requiring renal replacement therapy (RRT), particularly in urban areas with high rates of poverty and injection drug use. It is unknown how the widespread use of highly active antiretroviral therapy (HAART) has affected survival during RRT in this vulnerable population., Methods: African American patients infected with HIV-1 who required RRT were identified from 2 cohorts that included 4509 Africans Americans infected with HIV-1 who were recruited during the period 1988-2004 in Baltimore, Maryland. Survival after initiation of RRT was compared for those who initiated treatment in the pre-HAART and the HAART eras using Kaplan-Meier curves. Cox proportional hazards regression analysis was used to adjust for potential confounders., Results: RRT was initiated in 162 patients (3.6%) during 10.6 years of follow-up (119 during the HAART era). Compared with patients who started RRT in the pre-HAART era, those in the HAART era were older (P<.001) and more likely to have CD4 cell counts of

Adherence and retention of female injection drug users (IDUs) in clinical trials are not well known and were evaluated among 458 female IDUs in a clinical trial in Baltimore. Of all, 62.9% were adherent to visits (attended > or = 80% of visits). Of women with > or = 1 visit after enrollment, 76% were adherent to treatment (took > or = 80% of pills); 27.7% were lost to follow-up (missed > or = 3 consecutive visits). Women nonadherent to visits were younger and less likely to be on methadone. Women lost to follow-up were younger, more often white, not on methadone, and injecting drugs daily. Fair-moderate adherence to visits and treatment occurs among female IDUs in a clinical trial.