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BackgroundParticipant attrition in HIV longitudinal studies may introduce bias and diminish research quality. The identification of participant characteristics that are predictive of attrition might inform retention strategies.ObjectiveThe study aimed to identify factors associated with attrition among HIV-infected Russian risky drinkers from the secondary HIV prevention HERMITAGE trial. We examined whether current injection drug use (IDU), binge drinking, depressive symptoms, HIV status nondisclosure, stigma, and lifetime history of incarceration were predictors of study attrition. We also explored effect modification due to gender.MethodsComplete loss to follow-up (LTFU), defined as no follow-up visits after baseline, was the primary outcome, and time to first missed visit was the secondary outcome. We used multiple logistic regression models for the primary analysis, and Cox proportional hazards models for the secondary analysis.ResultsOf 660 participants, 101 (15.3%) did not return after baseline. No significant associations between independent variables and complete LTFU were observed. Current IDU and HIV status nondisclosure were significantly associated with time to first missed visit (adjusted hazard ratio [AHR], 1.39; 95% CI, 1.03-1.87; AHR, 1.38; 95% CI, 1.03-1.86, respectively). Gender stratified analyses suggested a larger impact of binge drinking among men and history of incarceration among women with time to first missed visit.ConclusionsAlthough no factors were significantly associated with complete LTFU, current IDU and HIV status nondisclosure were significantly associated with time to first missed visit in HIV-infected Russian risky drinkers. An understanding of these predictors may inform retention efforts in longitudinal studies.

OBJECTIVE: To examine the effect of smoking regulations in local restaurants on anti-smoking attitudes and quitting behaviours among adult smokers. DESIGN: Hierarchical linear modelling (HLM) was used to assess the relationship between baseline strength of town-level restaurant smoking regulation and follow-up (1) perceptions of the social acceptability of smoking and (2) quitting behaviours. SETTING: Each of the 351 Massachusetts towns was classified as having strong (complete smoking ban) or weak (all other and no smoking restrictions) restaurant smoking regulations. SUBJECTS: 1712 adult smokers of Massachusetts aged > or = 18 years at baseline who were interviewed via random-digit-dial telephone survey in 2001-2 and followed up 2 years later. MAIN OUTCOME MEASURES: Perceived social acceptability of smoking in restaurants and bars, and making a quit attempt and quitting smoking. RESULTS: Among adult smokers who had made a quit attempt at baseline, living in a town with a strong regulation was associated with a threefold increase in the odds of making a quit attempt at follow-up (OR = 3.12; 95% CI 1.51 to 6.44). Regulation was found to have no effect on cessation at follow-up. A notable, although marginal, effect of regulation was observed for perceiving smoking in bars as socially unacceptable only among smokers who reported at baseline that smoking in bars was socially unacceptable. CONCLUSIONS: Although local restaurant smoking regulations did not increase smoking cessation rates, they did increase the likelihood of making a quit attempt among smokers who had previously tried to quit, and seem to reinforce anti-social smoking norms among smokers who already viewed smoking in bars as socially unacceptable. [ABSTRACT FROM AUTHOR]

Background: The efficacy of brief intervention in reducing alcohol consumption is well established for selected outpatients but not for medical inpatients.Objective: To determine whether brief intervention improves alcohol outcomes in medical inpatients who were identified by screening as having unhealthy alcohol use.Design: Randomized, controlled trial.Setting: Medical service of an urban hospital.Patients: 341 medical inpatients who were drinking risky amounts of alcohol (defined for eligibility as >14 drinks/wk or > or =5 drinks/occasion for men and >11 drinks/wk or > or =4 drinks/occasion for women and persons > or =66 y); 77% had alcohol dependence as determined by the Composite International Diagnostic Interview Alcohol Module.Intervention: A 30-minute session of motivational counseling given by trained counselors during a patient's hospitalization (n = 172) versus usual care (n = 169).Measurements: Self-reported primary outcomes were receipt of alcohol assistance (for example, alcohol disorders specialty treatment) by 3 months in dependent drinkers and change in the mean number of drinks per day from enrollment to 12 months in all patients.Results: The intervention was not significantly associated with receipt of alcohol assistance by 3 months among alcohol-dependent patients (adjusted proportions receiving assistance, 49% for the intervention group and 44% for the control group; intervention-control difference, 5% [95% CI, -8% to 19%]) or with drinks per day at 12 months among all patients (adjusted mean decreases, 1.5 for patients who received the intervention and 3.1 for patients who received usual care; adjusted mean group difference, -1.5 [CI, -3.7 to 0.6]). There was no significant interaction between the intervention and alcohol dependence in statistical models predicting drinks per day (P = 0.24).Limitations: Baseline imbalances existed between randomized groups. Patients who received usual care were assessed and advised that they could discuss their drinking with their physicians.Conclusions: Brief intervention is insufficient for linking medical inpatients with treatment for alcohol dependence and for changing alcohol consumption. Medical inpatients with unhealthy alcohol use require more extensive, tailored alcohol interventions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Research on addiction treatment utilization in indigent samples mainly has been retrospective, without measures of addictive consequences, social network influences, and motivation. Prospective assessment of factors influencing utilization could inform policy and clinical care. OBJECTIVE: We sought to identify factors associated with utilization of addiction treatment and mutual help groups among substance-dependent persons with high rates of homelessness. RESEARCH AND METHODS: This was a prospective cohort of patients detoxified from alcohol or drugs at baseline who were followed for 2 years in a randomized clinical trial of linkage to primary care (n = 274). Outcomes included utilization of Inpatient/Residential, Outpatient, Any Treatment, and Mutual Help Groups. Predictor variables in longitudinal regression analyses came from the literature and clinical experience, organized according to theoretical categories of Need, and non-Need (eg, Predisposing and Enabling). RESULTS: Many subjects used Inpatient/Residential (72%), Outpatient (62%), Any Treatment (88%) or Mutual Help Groups (93%) at least once. In multivariable analyses, addictive consequences (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.12-1.71), motivation (OR 1.32, 95% CI 1.09-1.60), and female gender (OR 1.80, 95% CI 1.13-2.86) were associated with most treatment types (ORs are for Any Treatment). Homelessness was associated with Residential/Inpatient (for Chronically Homeless vs. Housed, OR 1.75, 95% CI 1.04-2.94). Living with one's children (OR 0.51, 95% CI 0.31-0.84) and substance-abusing social environment (OR 0.65, 95% CI 0.43-0.98) were negatively associated with Any Treatment. CONCLUSIONS: In this cohort of substance-dependent persons, addictive consequences, social network variables, and motivation were associated with treatment utilization. Non-need factors, including living with one's children and gender, also were significant. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess compliance with Boston's 100% smoke-free bar regulation within the first 3 months of implementation. An observational survey was conducted of a random sample of 102 bars in Boston before and after the smoking ban went into effect. Forty bars were observed both pre- and postban, serving as a true comparison group; 62 additional bars were observed postban only. From preban to postban, highly significant decreases were found in the mean proportion of patrons smoking inside (22.5% to 0.19%, p < 0.0001), in the proportion of bars with smoking patrons (100% to 2.5%, p < 0.0001), and in the average number of ashtrays present in each bar (24 to 0, p < 0.0001). A highly significant increase was found in the average number of 'no smoking' signs posted in each bar (0 to 3.3, p < 0.0001). Within the 3 months immediately following the 100% smoke-free bar regulation in Boston, bars were highly compliant with the ban, including not allowing patrons and employees to smoke, removing ashtrays, and posting signs indicating that smoking is prohibited. Therefore, with proper time and preparation, public health practitioners can change social norms before a ban goes into effect and can implement smoke-free policies smoothly and with immediate compliance. [ABSTRACT FROM AUTHOR]

Objectives. To determine whether the Communities That HEAL (CTH) intervention is effective in increasing naloxone distribution compared with usual care. Methods. The HEALing (Helping to End Addiction Long-Term) Communities Study (HCS) is a cluster-randomized, parallel-arm, wait-list controlled implementation science trial testing the impact of the CTH intervention on increasing the use of evidence-based practices to lower opioid-related overdose deaths. Communities (n = 67) highly impacted by opioid overdose in Kentucky, Massachusetts, New York, and Ohio were allocated to CTH intervention (n = 34) or wait-list comparison (usual care; n = 33) arms. The primary outcome for this study was the number of naloxone units distributed in HCS communities during the comparison period (July 1, 2021‒June 30, 2022), examined using an intent-to-treat negative binomial regression model. Results. Naloxone distribution was 79% higher in the CTH intervention versus usual care arm (adjusted relative rate = 1.79; 95% confidence interval = 1.28, 2.51; P  = .001; adjusted rates of naloxone distribution 3378 vs 1884 naloxone units per 100 000 residents), when controlling for urban‒rural status, state, baseline opioid-related overdose death rate, and baseline naloxone distribution rate. Conclusions. The CTH intervention increased naloxone distribution compared with usual care in communities highly impacted by the opioid crisis. Trial Registration. ClinicalTrials.gov identifier: NCT04111939. ( Am J Public Health . 2025;115(1):83-94. https://doi.org/10.2105/AJPH.2024.307845).

Water stress, a significant abiotic stressor, significantly hampers crop growth and yield, posing threat to food security. Despite the promising potential of nanoparticles (NPs) in enhancing plant stress tolerance, the precise mechanisms underlying the alleviation of water stress using O-Carboxymethyl chitosan nanoparticles (O-CMC-NPs) in maize remain elusive. In this study, we synthesized O-CMC-NPs and delved into their capacity to mitigate water stress (waterlogging and drought) in maize seedlings. Structural characterization revealed spherical O-CMC-NPs with a size of approximately 200 nm. These NPs accumulated near the seed embryo and root tip, resulting in a substantial increase in fresh and dry weights. The application of O-CMC-NPs to water-stressed maize seedlings remarkedly elevated the chlorophyll content and activity of various antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and polyphenol oxidase (PPO). The malondialdehyde (MDA) content was significantly reduced compared to the untreated control. Additionally, the expression of stress-responsive genes, such as ZmSOD, ZmCAT, ZmPOD, ZmTIFY, ZmACO, ZmPYL2, ZmNF-YC12, and ZmEREB180, were significantly upregulated in the O-CMC-NPs treated seedlings. These findings unveil the novel role of O-CMC-NPs in enhancing plant stress tolerance, suggesting their potential application in safeguarding maize seedlings under water stress conditions and facilitating the recovery from oxidative damage., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alcohol use is an important factor in achieving and maintaining viral suppression and optimal mental health among persons with HIV (PWH), however, the effect of age at first regular drinking on viral suppression and depression remains poorly understood. Here, using secondary data from the Alcohol Drinkers' Exposure to Preventive Therapy for Tuberculosis (ADEPT-T) study, we used logistic regression analyses to explore whether there is an association between age at first regular drinking and viral suppression (< 40 copies/ml), or presence of depressive symptoms (Center for Epidemiologic Studies Depression, CES-D ≥ 16) among 262 PWH. The median age at first regular drinking was 20.5 years (IQR: 10), with high proportions starting under age 12 (12.2%) and as teens (13.4%). The majority had an undetectable viral load (91.7%) and 11% had symptoms of probable depression. We found no significant association between age at first regular drinking and viral suppression (i.e., child (aOR = 0.76 95%CI: 0.18, 3.26), adolescent (aOR = 0.74 95%CI: 0.18, 2.97) and young adult (aOR = 1.27 95%CI: 0.40, 3.97)) nor with depressive symptoms (i.e., child (aOR = 0.72 95%CI: 0.19, 2.83), adolescent (aOR = 0.59 95%CI: 0.14, 2.50) and young adult (aOR = 0.57 95%CI: 0.22, 1.53)). Age at first regular drinking among PWH did not appear to be associated with either viral suppression or the presence of depressive symptoms, suggesting interventions may best be focused on the harmful effects of current alcohol use., (© 2023. The Author(s).)

Background: To estimate the effects on pain of two medications (low-dose naltrexone and gabapentin) compared to placebo among people with HIV (PWH) with heavy alcohol use and chronic pain., Methods: We conducted a pilot, randomized, double-blinded, 3-arm study of PWH with chronic pain and past-year heavy alcohol use in 2021. Participants were recruited in St. Petersburg, Russia, and randomized to receive daily low-dose naltrexone (4.5mg), gabapentin (up to 1800mg), or placebo. The two primary outcomes were change in self-reported pain severity and pain interference measured with the Brief Pain Inventory from baseline to 8 weeks., Results: Participants (N = 45, 15 in each arm) had the following baseline characteristics: 64% male; age 41 years (SD±7); mean 2 (SD±4) heavy drinking days in the past month and mean pain severity and interference were 3.2 (SD±1) and 3.0 (SD±2), respectively. Pain severity decreased for all three arms. Mean differences in change in pain severity for gabapentin vs. placebo, and naltrexone vs. placebo were -0.27 (95% confidence interval [CI] -1.76, 1.23; p = 0.73) and 0.88 (95% CI -0.7, 2.46; p = 0.55), respectively. Pain interference decreased for all three arms. Mean differences in change in pain interference for gabapentin vs. placebo, and naltrexone vs. placebo was 0.16 (95% CI -1.38, 1.71; p = 0.83) and 0.40 (95% CI -1.18, 1.99; p = 0.83), respectively., Conclusion: Neither gabapentin nor low-dose naltrexone appeared to improve pain more than placebo among PWH with chronic pain and past-year heavy alcohol use., Clinical Trial Registration: ClinicalTrials.gov (NCT4052139)., Competing Interests: Employees of the funder NIH (K. Bryant and M. Backonja) are co-authors on this manuscript and helped guide analysis, interpretation and presentation of data and participated in the decision to submit the manuscript for publication. The funder provided support in the form of salaries for authors [K. Bryant, M. Backonja], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. D. Cheng serves on Data Safety Monitoring Boards for Janssen Research & Development. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The remaining authors report no conflicts of interest., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Importance: Buprenorphine significantly reduces opioid-related overdose mortality. From 2002 to 2022, the Drug Addiction Treatment Act of 2000 (DATA 2000) required qualified practitioners to receive a waiver from the Drug Enforcement Agency to prescribe buprenorphine for treatment of opioid use disorder. During this period, waiver uptake among practitioners was modest; subsequent changes need to be examined., Objective: To determine whether the Communities That HEAL (CTH) intervention increased the rate of practitioners with DATA 2000 waivers and buprenorphine prescribing., Design, Setting, and Participants: This prespecified secondary analysis of the HEALing Communities Study, a multisite, 2-arm, parallel, community-level, cluster randomized, open, wait-list-controlled comparison clinical trial was designed to assess the effectiveness of the CTH intervention and was conducted between January 1, 2020, to December 31, 2023, in 67 communities in Kentucky, Massachusetts, New York, and Ohio, accounting for approximately 8.2 million adults. The participants in this trial were communities consisting of counties (n = 48) and municipalities (n = 19). Trial arm randomization was conducted using a covariate constrained randomization procedure stratified by state. Each state was balanced by community characteristics including urban/rural classification, fatal opioid overdose rate, and community population. Thirty-four communities were randomized to the intervention and 33 to wait-list control arms. Data analysis was conducted between March 20 and September 29, 2023, with a focus on the comparison period from July 1, 2021, to June 30, 2022., Intervention: Waiver trainings and other educational trainings were offered or supported by the HEALing Communities Study research sites in each state to help build practitioner capacity., Main Outcomes and Measures: The rate of practitioners with a DATA 2000 waiver (overall, and stratified by 30-, 100-, and 275-patient limits) per 100 000 adult residents aged 18 years or older during July 1, 2021, to June 30, 2022, were compared between the intervention and wait-list control communities. The rate of buprenorphine prescribing among those waivered practitioners was also compared between the intervention and wait-list control communities. Intention-to-treat and per-protocol analyses were performed., Results: A total of 8 166 963 individuals aged 18 years or older were residents of the 67 communities studied. There was no evidence of an effect of the CTH intervention on the adjusted rate of practitioners with a DATA 2000 waiver (adjusted relative rate [ARR], 1.04; 95% CI, 0.94-1.14) or the adjusted rate of practitioners with a DATA 2000 waiver who actively prescribed buprenorphine (ARR, 0.97; 95% CI, 0.86-1.10)., Conclusions and Relevance: In this randomized clinical trial, the CTH intervention was not associated with increases in the rate of practitioners with a DATA 2000 waiver or buprenorphine prescribing among those waivered practitioners. Supporting practitioners to prescribe buprenorphine remains a critical yet challenging step in the continuum of care to treat opioid use disorder., Trial Registration: ClinicalTrials.gov Identifier: NCT04111939.

Few studies have examined the association between healthcare utilization and heavy alcohol use in Russia among persons with HIV (PWH), a group with high healthcare needs. This study analyzed the association between unhealthy alcohol use (defined as AUDIT score ≥ 8) and healthcare utilization among PWH with heavy alcohol use and daily smoking in St. Petersburg, Russia. This secondary analysis used data from a randomized controlled trial addressing alcohol use. The primary outcome was seeing an infectionist for HIV care in the past year. Outcomes were measured at baseline, 6 months, and 12 months. We assessed the association between unhealthy alcohol use and healthcare utilization outcomes with a repeated measures logistic regression model, controlling for relevant covariates. Nearly all (96.0%) participants had unhealthy alcohol use at baseline, and 90.0% had seen an infectionist for HIV care in the past year. In adjusted analyses, unhealthy alcohol use was associated with a 36% decrease in seeing an infectionist for HIV care (aOR = 0.64, 95% CI 0.43-0.95). Participants reported low levels of emergency department visits and hospitalizations. Understanding how to engage this population in alcohol use disorder treatment and HIV care is an important next step for improving health outcomes for this population., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Stigma that people with HIV who inject drugs experience negatively impacts HIV and substance use care, but stigma's association with sharing injection equipment is not known. This is a cross-sectional analysis of data from two studies of people with HIV reporting drug injection ( N  = 319) in St. Petersburg, Russia (September 2018-December 2020). We used logistic regression to examine associations between HIV stigma and substance use stigma scores (categorised into quartiles) and past 30-day equipment sharing, adjusting for demographic and clinical characteristics. Secondary analyses examined associations of arrest history and social support with sharing equipment. Almost half (48.6%) of participants reported sharing injection equipment. Among groups who did and did not share, mean HIV stigma (2.3 vs 2.2) and substance use stigma (32 vs 31) scores were similar. Adjusted analyses detected no significant associations between HIV stigma quartiles (global p -value = 0.85) or substance use stigma quartiles (global p -value = 0.51) and sharing equipment. Neither arrest history nor social support were significantly associated with sharing equipment. In this cohort, sharing injection equipment was common and did not vary based on stigma, arrest history, or social support. To reduce equipment sharing, investments in sterile injection equipment access in Russia should be prioritised over interventions to address stigma.

Introduction: More than 70% of new HIV diagnoses in the United States were among men who have sex with men (MSM) in 2019. Pre-exposure prophylaxis (PrEP) is a transformative innovation for reducing human immunodeficiency virus (HIV) infections. Structural stigma against sexual minorities, including in the form of state-level policies, may affect PrEP implementation. We evaluated whether lower structural stigma reflected by earlier year of state same-sex marriage legalization was associated with increased male PrEP prescriptions and male PrEP-to-need ratio (PnR), a ratio of PrEP prescriptions to new HIV diagnoses., Methods: We used 2012-2019 AIDSVu data on male PrEP prescriptions and male PnR in each US state and year. We used generalized estimating equations to evaluate the relationship between the timing of implementing state same-sex marriage policies and the outcomes of male PrEP prescriptions per 100,000 people and the male PnR. We adjusted for calendar year, Medicaid expansion and the political party of the governor in each state., Results: State implementation of same-sex marriage policies in earlier, relative to later, periods was associated with increases in the rate of male PrEP prescriptions and in the male PnR. Specifically, implementing state same-sex marriage policies between 2004 and 2011 and between 2012 and 2013 were each associated with greater rates of male PrEP prescriptions relative to implementing same-sex marriage policies between 2014 and 2015. Implementing state same-sex marriage policies between 2004 and 2011 as well as between 2012 and 2013 were both significantly associated with a greater male PnR relative to implementing same-sex marriage policies between 2014 and 2015. By 2019, the difference in male PrEP prescriptions was 137.9 (97.3-175.5) per 100,000 in states that implemented same-sex marriage in 2004-2011 and 27.2 (23.3-30.5) per 100,000 in states that implemented same-sex marriage from 2012 to 2013, relative to states that implemented same-sex marriage in 2014-2015., Conclusions: Earlier implementation of state same-sex marriage policies was associated with greater rates of male PrEP prescriptions. Reducing state-level structural stigma may improve HIV prevention among MSM in the United States., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Providers' disrespect and abuse of patients is a recognized but understudied issue affecting quality of care and likely affecting healthcare utilization. Little research has examined this issue among people living with HIV (PWH) who inject drugs, despite high stigmatization of this population. No research has examined this issue in the context of Russia. This study assesses patients' reports of disrespect and abuse from providers as a barrier to healthcare and examines the association between these reports and HIV care outcomes.We conducted a cross-sectional analysis of the associations between disrespect/abuse from health providers as a barrier to care and the following HIV care outcomes: (i) anti-retroviral treatment (ART) uptake ever, (ii) past 6-month visit to HIV provider, and (iii) CD4 count. Participants (N = 221) were people living with HIV who injected drugs and were not on ART at enrollment.Two in five participants (42%) reported a history disrespect/abuse from a healthcare provider that they cited as a barrier to care. Those reporting this concern had lower odds of ever use of ART (adjusted odds ratio 0.46 [95% CI 0.22, 0.95]); we found no significant associations for the other HIV outcomes. We additionally found higher representation of women among those reporting prevalence of disrespect/abuse from provider as a barrier to care compared to those not reporting this barrier (58.1% versus 27.3%).Almost half of this sample of PWH who inject drugs report disrespect/abuse from a provider as a barrier to healthcare, and this is associated with lower odds of receipt of ART but not with other HIV outcomes studied. There is need for improved focus on quality of respectful and dignified care from providers for PWH who inject drugs, and such focus may improve ART uptake in Russia., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Antiretroviral therapy (ART) coverage in Russia is low for people with HIV who inject drugs. HIV and addiction treatment in Russia are not well integrated. We aimed to evaluate an intervention to link people with HIV in addiction treatment to HIV care to achieve HIV viral load suppression., Methods: LINC-II was a two-arm, open-label, randomised controlled trial at the City Addiction Hospital, Saint Petersburg, Russia. Eligible participants were aged 18 years or older, had a positive HIV status, were not currently on ART, were admitted to a narcology hospital, and had a current diagnosis of opioid use disorder. Participants were randomly assigned (1:1) to a multicomponent intervention (ie, rapid access to ART, naltrexone for opioid use disorder, and strengths-based case management) or standard of care. Blocked randomisation was stratified by history of ART use. The primary outcome was undetectable HIV viral load at 12 months, defined as less than 40 copies per mL. The trial was conducted and analysed according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, NCT03290391., Findings: Between Sept 19, 2018, and Dec 25, 2020, 953 individuals were screened for eligibility, 225 of whom were randomly assigned to the intervention (n=111) or standard of care (n=114). 136 (60%) participants were male and 89 (40%) were female. Participants in the intervention group had higher odds of HIV viral load suppression at 12 months compared with participants in the standard-of-care group (52 [47%] vs 26 [23%]; adjusted odds ratio 3·0 [95% CI 1·4-6·4]; p=0·0039). 21 adverse events (18 in the intervention group and three in the standard-of-care group)and 14 deaths (four in the intervention group and ten in the standard-of-care group) were reported in the study., Interpretation: Given the effectiveness of the LINC-II intervention, scaling up this model could be one strategy to advance the UNAIDS goal of ending the HIV epidemic., Funding: National Institute on Drug Abuse and Providence/Boston Center for AIDS Research., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03278886.

Objective: Isoniazid (INH) preventive therapy is recommended to prevent tuberculosis (TB) disease for persons with HIV (PWH), except for those with regular and heavy alcohol consumption, due to hepatotoxicity concerns. We aimed to quantify the incidence of severe INH-related toxicity among PWH with and without recent alcohol consumption., Design: A prospective study of PWH receiving INH., Methods: We included PWH in southwest Uganda with recent (prior 3 months) ( n  = 200) or no (prior year) self-reported alcohol consumption ( n  = 101), on antiretroviral therapy, TB infected (≥5 mm on tuberculin skin test), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 2× or less the upper limit of normal (ULN). Grade 3+ INH-related toxicity was ALT or AST at least 5× the ULN or severe symptoms; we stopped IPT upon detection. Grade 2 INH-related toxicity was ALT or AST 2-5× the ULN or moderate symptoms., Results: The cumulative incidence of Grade 3+ INH-related toxicity was 8.3% [95% confidence interval (95% CI) 5.4-12.0]; all resolved after INH cessation. Incidence was 6.0% (95% CI 3.1-10.2) among those reporting recent alcohol use and 12.9% (95% CI 7.0-21.0) among those reporting no prior year alcohol use. We found no differences by baseline phosphatidylethanol-confirmed alcohol severity. The cumulative incidence of Grade 2 toxicities (without Grade 3+) was 21.7% (95% CI 17.0-27.1); 25.0% (95% CI 19.0-31.8) among those with recent alcohol use and 14.8% (95% CI 8.1-23.9) among those with no prior year alcohol use., Conclusion: Alcohol use does not appear to increase risk for serious INH-related toxicity among PWH without significant liver enzyme elevations at baseline (≤2x ULN)., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Food insecurity (FI) impacts people with HIV (PWH) and those who use substances (i.e. drugs and alcohol). We evaluated the longitudinal association between FI and HIV transmission risks (unprotected sexual contacts and shared needles/syringes). Among 351 PWH who use substances in Russia, 51.6% reported FI and 37.0% past month injection drug use. The mean number of unprotected sexual contacts in the past 90 days was 13.4 (SD 30.1); 9.7% reported sharing needles/syringes in the past month. We did not find a significant association between mild/moderate FI (adjusted IRR = 0.87, 95% CI 0.47, 1.61) or severe FI (aIRR = 0.84, 95% CI 0.46, 1.54; global p = 0.85) and unprotected sexual contacts. We observed a significant association between severe FI and sharing needles/syringes in the past month (adjusted OR = 3.27, 95% CI 1.45, 7.39; p = 0.004), but not between mild/moderate FI and sharing needles/syringes in the past month (aOR = 1.40,95% CI 0.58, 3.38; p = 0.45). These findings suggest that severe FI could be a potential target for interventions to lower HIV transmission., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alcohol use is especially problematic for people living with HIV (PLWH) and was likely to be impacted by the coronavirus disease (COVID-19) pandemic and its restrictions. In a study of PLWH with latent tuberculosis infection, we measured unhealthy alcohol use with the Alcohol Use Disorders Identification Test (AUDIT-C), phosphatidylethanol (PEth) and bar attendance. We analyzed data collected before and after COVID-19 restrictions, and used Generalized Estimating Equations (GEE) logistic regression models to evaluate changes in unhealthy alcohol use. While bar attendance declined from 57.0% before to 38.3% after the restrictions started, multivariable analysis controlling for bar use showed a significant increase in unhealthy alcohol use; the adjusted odds ratio for unhealthy drinking before versus after the restrictions started was 1.37 (95% CI: 0.89-2.12) which increased to 1.64 (95% CI: 1.08-2.50) when bar attendance was added to the model. Decline in bar attendance did not decrease unhealthy alcohol use., (© 2022. The Author(s).)

Background: The HIV epidemic is intertwined with substance use and incarceration in Russia. The relationships between incarceration history, HIV treatment history, and stigma experiences among people with HIV (PWH) who inject drugs in Russia have not been well described., Methods: We conducted a cross-sectional study of a cohort of PWH with opioid use disorder who inject drugs (n=201) recruited at a narcology (substance use treatment) hospital in St. Petersburg, Russia from September 2018 to December 2020. The primary analysis evaluated the association between self-reported prior incarceration and prior antiretroviral therapy (ART) initiation using multivariable logistic regression to adjust for demographic, social, and clinical covariates. We used multivariable linear regression models to analyze associations between prior incarceration and two secondary outcomes: HIV stigma score (11-item abbreviated Berger scale) and substance use stigma score (21-item combination of Substance Abuse Self-Stigma Scale and Stigma-related Rejection Scale)., Results: Mean age was 37 (SD 5) years; 58.7% were male. Participants had been living with HIV for a mean of 13 (SD 6) years. Over two thirds (69.2%) of participants reported prior incarceration. One third (35.3%) of participants reported prior ART initiation. Prior incarceration was not significantly associated with prior ART initiation (AOR 1.76; 95% CI: 0.81, 3.83). Prior incarceration was associated with a lower HIV stigma score (adjusted mean difference in z-score: -0.50; 95%CI: -0.81, -0.19) but was not significantly associated with substance use stigma score (adjusted mean difference in z-score: -0.10; 95%CI: -0.42, 0.21)., Conclusion: Prior incarceration was common, and rates of prior ART initiation were low even though most participants had been living with HIV for at least a decade. We did not find an association between prior incarceration and prior ART initiation, which suggests a need to explore whether opportunities to initiate ART during or after incarceration are missed., Clinical Trial Number: NCT03290391., Competing Interests: Declarations of Interests The authors have no potential conflicts of interest to report., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Unhealthy alcohol use is associated with increased progression to tuberculosis (TB) disease, but its effect on adherence to isoniazid (INH) preventive therapy is not known., Methods: This was a prospective study of persons with HIV with latent TB in southwestern Uganda reporting any current (previous 3 months) alcohol use or no alcohol consumption in the previous year (2:1 ratio). All received INH. We defined suboptimal adherence as <90% of days with at least 1 Medication Event Monitoring System cap opening, over the previous 90 days. Alcohol use was categorized as follows: none: no self-report and phosphatidylethanol (PEth) <8 ng/mL; moderate: Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) 1-2 (women) or 1-3 (men) and/or PEth 8 ≥ 50 ng/mL; and unhealthy: AUDIT-C ≥3 (women) or ≥4 (men) and/or PEth ≥50 ng/mL. We used generalized estimating equation logistic regression analyses to assess the association between the level of alcohol use and suboptimal INH adherence., Results: Three hundred two persons were enrolled; 279 were on INH for 3 or more months. The prevalence of suboptimal INH adherence was 31.3% at 3 months and 43.9% at 6 months. The odds of suboptimal INH adherence were higher for unhealthy (adjusted odds ratio, 2.78; 95% confidence interval: 1.62 to 4.76) and moderate (adjusted odds ratio, 1.59; 95% confidence interval: 0.94 to 2.71) compared with no alcohol consumption., Conclusions: Suboptimal adherence to INH at 3 and 6 months was high among prospective study of persons with HIV and associated with unhealthy alcohol use. Adherence support and alcohol reduction strategies are needed for this group at high risk for active TB., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

This study evaluated the association between impulsivity and linkage to HIV care among Russians living with HIV recruited from an inpatient narcology hospital. Linking Infectious and Narcology Care (LINC) study participants who completed the Barratt Impulsiveness Scale (BIS) were included in these analyses. The primary independent variable was impulsivity score which was categorized as high impulsivity (BIS score > 71) vs. low impulsivity (BIS score < = 71). The primary outcome, linkage to care post recruitment, was defined as one or more HIV medical care visits at 12-month follow-up. Multiple logistic regression models were used to evaluate the association between high impulsivity and linkage to HIV care controlling for potential confounders. Participants (N = 227) were adults with a mean age of 34 years (SD = 5), and the majority were male (74%). We did not detect a significant association between impulsivity and linkage to HIV care after adjusting for respondents' age, gender, CD4 cell count, and depression score. We also found that substance use and hazardous drinking did not appear to confound the relationship. Although our study was unable to detect an association between impulsivity and linkage to HIV care, it may provide direction for future research exploring the associations between impulsivity and HIV care., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The HEALing (Helping to End Addiction Long-term SM ) Communities Study (HCS) is a multi-site parallel group cluster randomized wait-list comparison trial designed to evaluate the effect of the Communities That Heal (CTH) intervention compared to usual care on opioid overdose deaths. Covariate-constrained randomization (CCR) was applied to balance the community-level baseline covariates in the HCS. The purpose of this paper is to evaluate the performance of model-based tests and permutation tests in the HCS setting. We conducted a simulation study to evaluate type I error rates and power for model-based and permutation tests for the multi-site HCS as well as for a subgroup analysis of a single state (Massachusetts). We also investigated whether the maximum degree of imbalance in the CCR design has an impact on the performance of the tests., Methods: The primary outcome, the number of opioid overdose deaths, is count data assessed at the community level that will be analyzed using a negative binomial regression model. We conducted a simulation study to evaluate the type I error rates and power for 3 tests: (1) Wald-type t-test with small-sample corrected empirical standard error estimates, (2) Wald-type z-test with model-based standard error estimates, and (3) permutation test with test statistics calculated by the difference in average residuals for the two groups., Results: Our simulation results demonstrated that Wald-type t-tests with small-sample corrected empirical standard error estimates from the negative binomial regression model maintained proper type I error. Wald-type z-tests with model-based standard error estimates were anti-conservative. Permutation tests preserved type I error rates if the constrained space was not too small. For all tests, the power was high to detect the hypothesized 40% reduction in opioid overdose deaths for the intervention vs. comparison group both for the overall HCS and the subgroup analysis of Massachusetts (MA)., Conclusions: Based on the results of our simulation study, the Wald-type t-test with small-sample corrected empirical standard error estimates from a negative binomial regression model is a valid and appropriate approach for analyzing cluster-level count data from the HEALing Communities Study., Trial Registration: ClinicalTrials.gov http://www., Clinicaltrials: gov ; Identifier: NCT04111939., (© 2022. The Author(s).)

Importance: Cigarette smoking and risky alcohol consumption co-occur and are undertreated. Nicotine receptor partial agonists and nicotine replacement therapy (NRT) treat smoking but are unproven for alcohol, and clinical trials rarely include individuals with HIV, substance use, and mental health conditions., Objective: To compare the effects on drinking and smoking of nicotinic acetylcholine receptor partial agonists varenicline and cytisine with those of NRT., Design, Setting, and Participants: This 4-group randomized, double-blinded, placebo-controlled clinical trial was conducted from July 2017 to December 2020 in St Petersburg, Russia. Included participants were 400 individuals with HIV who engaged in risky drinking (≥5 prior-month heavy-drinking days [HDDs]) and daily smoking; they were followed up for 12 months after enrollment. Data were analyzed from May 2021 through June 2022., Interventions: Participants received alcohol and tobacco counseling, 1 active medication, and 1 placebo in 1 of 4 groups: active varenicline and placebo NRT (group 1), placebo varenicline and active NRT (group 2), active cytisine and placebo NRT (group 3), or placebo cytisine and active NRT (group 4)., Main Outcomes and Measures: The primary outcome was number of prior-month HDDs at 3 months. Secondary outcomes included biochemically validated abstinence from alcohol at 3 months and smoking at 6 months., Results: Among 400 participants (263 [65.8%] men; mean [SD] age, 39 [6] years), 97 individuals (24.3%) used opioids and 156 individuals (39.1%) had depressive symptoms. These individuals had a mean (SD) CD4 count of 391 (257) cells/mm3, smoked a mean (SD) of 21 [8] cigarettes/d, and reported a mean (SD) of 9.3 (5.8) HDDs in the prior 30 days. At 3 months, the mean (SD) number of HDDs was decreased vs baseline across all groups (group 1: 2.0 [3.8] HDDs vs. 9.5 [6.1] HDDs; group 2: 2.1 [4.3] HDDs vs 9.3 [5.7] HDDs; group 3: 1.5 [3.3] HDDs vs 8.9 [5.0] HDDs; group 4: 2.4 [5.2] HDDs vs 9.6 [6.3] HDDs). There were no significant differences at 3 months between groups in mean (SD) HDDs, including group 1 vs 2 (incident rate ratio [IRR], 0.94; 95% CI, 0.49-1.79), 3 vs 4 (IRR, 0.60; 95% CI, 0.30-1.18), and 1 vs 3 (IRR, 1.29; 95% CI, 0.65-2.55). There were no significant differences at 6 months between groups in smoking abstinence, including group 1 vs 2 (15 of 100 individuals [15.0%] vs 17 of 99 individuals [17.2%]; odds ratio [OR],0.89; 95% CI, 0.38-2.08), 3 vs 4 (19 of 100 individuals [19.0%] vs 19 of 101 individuals [18.8%]; OR, 1.00; 95% CI, 0.46-2.17), and 1 vs 3 (OR, 0.79; 95% CI, 0.35-1.78). Post hoc analyses suggested lower mean (SD) HDDs (eg, at 3 months: 0.7 [1.8] HDDs vs 2.3 [4.6] HDDs) and higher alcohol abstinence (eg, at 3 months: 30 of 85 individuals [35.3%] vs 54 of 315 individuals [17.1%]) among those who quit vs continued smoking., Conclusions and Relevance: This study found that among individuals with HIV who engaged in risky drinking and smoking, varenicline and cytisine were not more efficacious than NRT to treat risky drinking and smoking but that behavior change rates were high in all groups., Trial Registration: ClinicalTrials.gov Identifier: NCT02797587.

Hazardous alcohol use and psychological distress are common among persons living with HIV (PLWH). In Uganda, HIV prevalence is 6.2% with average pure alcohol consumption per capita of 9.8 L. Social support may mitigate hazardous alcohol use. In a cohort of 443 PLWH, we measured social support using the Duke-UNC functional social support scale and self-reported alcohol consumption using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), augmented by phosphatidylethanol (PEth). We examined the association between low social support and hazardous alcohol use using multiple logistic regression models. 30% had low social support and 44% had hazardous alcohol use (AUDIT-C ≥ 3 for women and ≥ 4 for men and/or PEth ≥ 50 ng/mL). We did not detect an association between low social support and hazardous alcohol use. Social support may play no role or a minimal role in preventing PLWH from hazardous alcohol use., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: This work is motivated by the HEALing Communities Study, which is a post-test only cluster randomized trial in which communities are randomized to two different trial arms. The primary interest is in reducing opioid overdose fatalities, which will be collected as a count outcome at the community level. Communities range in size from thousands to over one million residents, and fatalities are expected to be rare. Traditional marginal modeling approaches in the cluster randomized trial literature include the use of generalized estimating equations with an exchangeable correlation structure when utilizing subject-level data, or analogously quasi-likelihood based on an over-dispersed binomial variance when utilizing community-level data. These approaches account for and estimate the intra-cluster correlation coefficient, which should be provided in the results from a cluster randomized trial. Alternatively, the coefficient of variation or R coefficient could be reported. In this article, we show that negative binomial regression can also be utilized when communities are large and events are rare. The objectives of this article are (1) to show that the negative binomial regression approach targets the same marginal regression parameter(s) as an over-dispersed binomial model and to explain why the estimates may differ; (2) to derive formulas relating the negative binomial overdispersion parameter k with the intra-cluster correlation coefficient, coefficient of variation, and R coefficient; and (3) analyze pre-intervention data from the HEALing Communities Study to demonstrate and contrast models and to show how to report the intra-cluster correlation coefficient, coefficient of variation, and R coefficient when utilizing negative binomial regression., Methods: Negative binomial and over-dispersed binomial regression modeling are contrasted in terms of model setup, regression parameter estimation, and formulation of the overdispersion parameter. Three specific models are used to illustrate concepts and address the third objective., Results: The negative binomial regression approach targets the same marginal regression parameter(s) as an over-dispersed binomial model, although estimates may differ. Practical differences arise in regard to how overdispersion, and hence the intra-cluster correlation coefficient is modeled. The negative binomial overdispersion parameter is approximately equal to the ratio of the intra-cluster correlation coefficient and marginal probability, the square of the coefficient of variation, and the R coefficient minus 1. As a result, estimates corresponding to all four of these different types of overdispersion parameterizations can be reported when utilizing negative binomial regression., Conclusion: Negative binomial regression provides a valid, practical, alternative approach to the analysis of count data, and corresponding reporting of overdispersion parameters, from community randomized trials in which communities are large and events are rare.

Phosphatidylethanol (PEth) is a sensitive and specific biomarker of alcohol consumption in the prior 2-3 weeks. Standard, manual PEth testing using dried blood spots (DBS) is a multi-step time-consuming process. A novel, automated processing and testing method has been developed to decrease DBS processing and testing time. We conducted automated testing, using regioisomerically pure PEth reference material, on randomly selected DBS, which had previously been tested via manual methods and then stored for 3-6 years at -80 °C, to compare the results (PEth 16:0/18:1 homologue). We chose samples for re-testing using categories found in the literature as follows: 1) PEth <20 ng/mL; 2) PEth 20-200 ng/mL; 3) PEth >200-1000 ng/mL; 4) PEth >1000 ng/mL. We calculated agreement between the categories using the weighted kappa statistic (n = 49 DBS). We quantified agreement between continuous measures using the intraclass correlation coefficient (ICC), and further described the relationship between variables using Spearman correlation. The median PEth result was 155 ng/mL (interquartile range [IQR]: 1-1312 ng/mL) via automated methods and 98.8 ng/mL (IQR: 10.2-625.0 ng/mL) via manual methods. The weighted kappa comparing the automated to manual PEth results was 0.76 [95% Confidence Interval (CI): 0.66-0.86]. The ICC was 0.69 (95% CI: 0.54-0.79), and the Spearman correlation was 0.98 (95% CI: 0.95-0.99). While the new methods yielded somewhat higher PEth values, we found good to excellent agreement between clinically relevant PEth categories. Automated DBS processing and testing using new reference standards are promising methods for PEth testing., Competing Interests: Declaration of competing interest Dr. Marc Luginbühl and Dr. Stefan Gaugler are employees of the DBS research laboratory at CAMAG (Muttenz, Switzerland), and did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors for this work. CAMAG donated the materials needed to do the automated testing., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: HIV clinicians report low confidence and satisfaction prescribing chronic opioid therapy (COT). We hypothesized that the Targeting Effective Analgesia in Clinics for HIV (TEACH) intervention [a system-level improvement to increase guideline concordant care for COT] would improve satisfaction, confidence, and trust among PWH and their clinicians., Methods: We conducted a two-arm, unblinded cluster randomized controlled trial (RCT) to assess the TEACH intervention. Clinicians were randomized in a 1:1 ratio to receive either the TEACH intervention (an IT-enabled nurse care manager, opioid education, academic detailing, and access to addiction specialists) or usual care. Outcomes were the following: clinician satisfaction (primary); confidence prescribing COT; patient satisfaction with COT; and trust in clinician. Intention-to-treat analyses were conducted using linear and logistic regression models., Results: Clinicians (n = 41) were randomized and their 114 patients assessed. At 12 months, the adjusted mean difference in satisfaction with COT was 1.11 points for intervention vs control clinicians (Scale 1-10; 95% confidence interval [CI]: -0.04 to 2.26, p = 0.06). The adjusted mean confidence with prescribing COT was 1.01 points higher among intervention clinicians (Scale 1-10; 95% CI: 0.05-1.96, p = 0.04). There were no significant differences in patient satisfaction with COT (adjusted odds ratio (AOR) 1.17, 95% CI: 0.50-2.76, p = 0.72) or trust in provider (AOR 1.63, 95% CI: 0.65-4.09, p = 0.30)., Conclusions: TEACH did not significantly affect prescriber satisfaction, patient satisfaction with pain management or patient trust; however, it did improve prescriber confidence. TEACH is a promising strategy to improve provider prescribing of COT for PWH without adverse patient satisfaction or trust in provider., (Copyright © 2022. Published by Elsevier B.V.)

Background: Chronic pain is prevalent among people living with human immunodeficiency virus (PLWH); managing pain with chronic opioid therapy (COT) is common. Human immunodeficiency virus (HIV) providers often diverge from prescribing guidelines., Methods: This 2-arm, unblinded, cluster-randomized clinical trial assessed whether the Targeting Effective Analgesia in Clinics for HIV (TEACH) intervention improves guideline-concordant care compared to usual care for PLWH on COT. The trial was implemented from 2015 to 2018 with 12-month follow-up at safety-net hospital-based HIV clinics in Boston and Atlanta. We enrolled 41 providers and their 187 patients on COT. Prescribers were randomized 1:1 to either a 12-month intervention consisting of a nurse care manager with an interactive electronic registry, opioid education, academic detailing, and access to addiction specialists or a control condition consisting of usual care. Two primary outcomes were assessed through electronic medical records: ≥2 urine drug tests and any early COT refills by 12 months. Other outcomes included possible adverse consequences., Results: At 12 months, the TEACH intervention arm had higher odds of ≥2 urine drug tests than the usual care arm (71% vs 20%; adjusted odds ratio [AOR], 13.38 [95% confidence interval {CI}, 5.85-30.60]; P < .0001). We did not detect a statistically significant difference in early refills (22% vs 30%; AOR, 0.55 [95% CI, .26-1.15]; P = .11), pain severity (6.30 vs 5.76; adjusted mean difference, 0.10 [95% CI, -1.56 to 1.75]; P = .91), or HIV viral load suppression (86.9% vs 82.1%; AOR, 1.21 [95% CI, .47-3.09]; P = .69)., Conclusions: TEACH is a promising intervention to improve adherence to COT guidelines without evident adverse consequences., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Little is known about the intersection of HIV stigma and substance use stigma. Using data from 188 HIV-positive people who inject drugs (PWID) in Russia, we examined the associations of these stigmas and their interaction with access and utilization of healthcare. While substance use stigma was significantly associated with poor access to care (AOR 2.31, 95%CI 1.50-3.57), HIV stigma was not. HIV stigma was associated with lower inpatient care utilization (AOR 0.32, 95%CI 0.14-0.65), while substance use stigma was not. We did not detect a significant interaction between the two forms of stigma for either of the primary outcomes. However, those with high levels of both substance use stigma and HIV stigma had higher odds of poor general access to healthcare (AOR 1.86, 95%CI 1.19-2.92), and lower odds of recent general outpatient (AOR 0.52, 95%CI 0.32-0.85) and any inpatient (AOR 0.48, 95%CI 0.22-0.99) care utilization compared to those with low levels of both types of stigma. Interventions addressing both substance use and HIV stigma in general healthcare settings might improve care in this HIV key population., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

This study describes the self-reported prevalence of hepatitis C virus (HCV) coinfection and the HCV care continuum among persons enrolled in the St PETER HIV Study, a randomized controlled trial of medications for smoking and alcohol cessation in HIV-positive heavy drinkers and smokers in St. Petersburg, Russia. Baseline health questionnaire data were used to calculate proportions and 95% confidence intervals for self-reported steps along the HCV continuum of care. The cohort included 399 HIV-positive persons, of whom 387 [97.0% (95% CI 95.3-98.7%)] reported a prior HCV test and 315 [78.9% (95% CI 74.9-82.9%)] reported a prior diagnosis of HCV. Among those reporting a diagnosis of HCV, 43 [13.7% (95% CI 9.9-17.4%)] had received treatment for HCV, and 31 [9.8% (95% CI 6.6-13.1%)] had been cured. Despite frequent HCV testing in this HIV-positive Russian cohort, the proportion reporting prior effective HCV treatment was strikingly low. Increased efforts are needed to scale-up HCV treatment among HIV-positive Russians in St. Petersburg.

Background: The risk of tuberculosis (TB) is high among people with HIV (PWH). Heavy alcohol drinking independently increases TB risk and approximately 25% of PWH globally engage in heavy drinking. While isoniazid (INH) preventive therapy decreases TB incidence and mortality among PWH, heavy drinking during INH is associated with liver toxicity and poor adherence. Interventions are, therefore, urgently needed to decrease alcohol use and improve adherence to INH in this population in settings with high prevalence of HIV and TB like Uganda., Methods: The Drinkers' Intervention to Prevent TB (DIPT) study is a 2×2 factorial randomized controlled trial among HIV/TB co-infected adults (≥18 years) who engage in heavy alcohol drinking and live in Uganda. The trial will allocate 680 participants with a 1:1:1:1 individual randomization to receive 6 months of INH and one of the following interventions: (1) no incentives (control), (2) financial incentives contingent on low alcohol use, (3) financial incentives contingent on high adherence to INH, and (4) escalating financial incentives for both decreasing alcohol use and increasing adherence to INH. Incentives will be in the form of escalating lottery-based monetary rewards. Participants will attend monthly visits to refill isoniazid medications, undergo liver toxicity monitoring, and, except for controls, determine eligibility for prizes. We will estimate (a) the effect of incentives contingent on low alcohol use on reduction in heavy drinking, measured via a long-term objective and self-reported metric of alcohol use, at 3- and 6-month study visits, and (b) the effect of incentives contingent on high adherence to INH, measured as >90% pill-taking days by medication event monitoring system cap opening. We will use qualitative methods to explore the mechanisms of any influence of financial incentives on HIV virologic suppression., Discussion: This study will provide new information on low-cost strategies to both reduce alcohol use and increase INH adherence among people with HIV and TB infection who engage in heavy drinking in low-income countries with high HIV and TB prevalence., Trial Registration: ClinicalTrials.gov NCT03492216 . Registered on April 10, 2018.

Background: The impact of Hepatitis C virus (HCV) RNA levels on the evolution of chronic HCV infection-related liver damage is controversial. Heavy alcohol use is believed to have a deleterious impact on the course of HCV disease, but current knowledge about the possible effect of alcohol use on HCV RNA levels in HIV/HCV coinfected patients is limited., Methods: We examined 107 HIV/HCV-infected individuals with current or past unhealthy alcohol use to assess the association between alcohol consumption (any drinking vs. abstinent) and HCV RNA levels., Results: Participants were 75% male, with a mean age of 43 years, and 63% were on antiretroviral therapy. Mean (SD) log HIV RNA was 3.1 (1.4) and mean (SD) log HCV RNA was 6.1 (0.8). Past-month alcohol use was present in 38% of participants. In a multivariable linear regression analysis we found no significant differences in mean log HCV RNA levels between those reporting alcohol use and those who were abstinent [β (95%CI): -0.04 (-0.34, 0.26), p = 0.79)]. There was no significant association between any heavy drinking day and HCV RNA level (0.07, 95% CI: (-0.24, 0.38), p = 0.66)., Conclusions: We did not detect significant associations between alcohol use and HCV RNA levels among HIV/HCV coinfected patients.

Background: The Zinc for INflammation and Chronic disease in HIV (ZINC) trial randomized person who live with HIV (PLWH) who engage in heavy drinking to either daily zinc supplementation or placebo. The primary outcome was change in the Veterans Aging Cohort Study (VACS) index, a predictor of mortality, between baseline and 18 months. Because adherence and follow-up were suboptimal, the intention-to-treat analysis, which was not statistically significant, may have underestimated the effect of the zinc supplementation., Objective: We estimated the per-protocol effect of zinc versus placebo in the ZINC trial (i.e., the effect that would have been observed if all participants had had high adherence and none was lost to follow-up)., Methods: Adherence was measured as the self-reported percentage of pills taken in the previous 6 weeks and assessed at all post-baseline visits. We used inverse probability weighting to estimate and compare the change in the VACS index at 18 months in the zinc and placebo groups, had all the trial participants had high adherence (i.e., cumulative adherence ≥80% at 18 months). To examine trends by level of adherence, we rerun the analyses using thresholds for high adherence of 70% and 90% of average self-reported pill coverage., Results: The estimated (95% confidence interval) change in the VACS index was - 2.16 (- 8.07, 3.59) and 5.84 (0.73, 11.80) under high adherence and no loss to follow-up in the zinc and placebo groups, respectively. The per-protocol effect estimate of the mean difference in the change between the zinc and placebo groups was - 8.01 (- 16.42, 0.01), somewhat larger than the intention-to-treat effect difference in change (- 4.68 (- 9.62, 0.25)), but it was still not statistically significant. The mean difference in the change between individuals in the zinc and placebo groups was - 4.07 (- 11.5, 2.75) and -12.34 (- 20.14, -4.14) for high adherence defined as 70% and 90% of pill coverage, respectively., Conclusions: Overall, high adherence to zinc was associated with a lower VACS score, but confidence intervals were wide and crossed 0. Further studies with a larger sample size are needed to quantify the benefits of zinc supplementation in this population., Trial Registration: ClinicalTrials.gov NCT01934803 . Registered on August 30, 2013.

Background: Alcohol use is common among persons living with HIV (PLWH), who often experience chronic pain, yet its impact on pain and opioid misuse is not fully characterized., Methods: We assessed associations between hazardous alcohol use and pain interference, defined as the self-reported impact of pain on daily living, pain severity, and risk for opioid misuse among PLWH who were on long-term opioid therapy (LTOT). A cohort was recruited as part of the "Targeting Effective Analgesia in Clinics for HIV" (TEACH) study, a randomized controlled trial to improve LTOT in HIV clinics. The Alcohol Use Disorders Test (AUDIT), Brief Pain Inventory (BPI) and the Current Opioid Misuse Measure (COMM) were administered at both baseline and 12-months. Linear mixed and generalized estimating equation models, incorporating data from both time points, evaluated associations between hazardous alcohol use (AUDIT ≥8) and: pain interference (0-10), pain severity (0-10), and opioid misuse risk (COMM ≥13), adjusting for age, gender, depressive symptoms, use of non-alcohol substances, time-point, and study-arm., Results: The sample was comprised of 166 participants, of which 31 (19%) reported hazardous alcohol use. The majority were male (65%), black (72%), and the mean age was 54 (range: 29-77). Hazardous alcohol use was significantly associated with higher pain interference (adjusted mean difference [AMD]: 1.02; 95% CI: 0.08, 1.96) and higher odds of opioid misuse risk (AOR: 3.73, 95% CI: 1.88-7.39), but not pain severity (AMD: 0.47, 95% CI: - 0.35, 1.29)., Conclusions: Hazardous alcohol use was associated with greater functional impairment in daily living from their pain and higher odds for prescription opioid misuse in this study of PLWH on LTOT. Providers should be attentive to alcohol use among PLWH who are prescribed opioids given associations with pain and opioid misuse., Trial Registration: ClinicalTrials.gov NCT02564341 (Intervention, September 30, 2015) and NCT02525731 (Patient Cohort, August 17, 2015). Both prospectively registered.

Background and Objectives: Previous findings on the association between hazardous drinking and HIV-risk behavior have been equivocal, varying by population and individual difference factors. This study examined associations between hazardous drinking, impulsivity, and HIV-risk behaviors among HIV-positive Russian patients with a history of injection drug use (IDU), not on antiretroviral therapy., Methods: Negative binomial regression analyses of data from a randomized controlled trial were performed (N = 241). Main independent variables were the Alcohol Use Disorders Identification Test and the Barratt Impulsiveness Scale. Outcomes were number of condomless sexual episodes (CSE; primary), number of sexual partners, and needle-sharing frequency (secondary)., Results: Hazardous drinking was positively associated with the frequency of CSE (adjusted incidence rate ratio [aIRR] = 2.16, 95% confidence interval [CI], 1.98-2.36). Moderate (aIRR = 0.51, 95% CI, 0.46-0.56) and high (aIRR = 0.66, 95% CI, 0.60-0.73) impulsivity were associated with fewer CSE compared with low impulsivity. Hazardous drinking (aIRR = 0.64, 95% CI, 0.52-0.79) and impulsivity (aIRR = 0.95, 95% CI, 0.94-0.96) were both associated with fewer sexual partners. Hazardous drinking and impulsivity were each associated with increased needle sharing. The association between hazardous drinking and number of needle-shares was strongest at higher impulsivity levels., Conclusion and Scientific Significance: Hazardous drinking may be a risk factor for CSE among HIV-positive Russian patients and may influence needle sharing. Findings contribute to our understanding of the interactive associations between hazardous drinking and impulsivity with sexual risk behaviors and needle sharing among HIV-positive Russian patients with a history of IDU. (Am J Addict 2020;00:00-00)., (© 2020 American Academy of Addiction Psychiatry.)

Background: Statistical methods for modeling longitudinal and time-to-event data has received much attention in medical research and is becoming increasingly useful. In clinical studies, such as cancer and AIDS, longitudinal biomarkers are used to monitor disease progression and to predict survival. These longitudinal measures are often missing at failure times and may be prone to measurement errors. More importantly, time-dependent survival models that include the raw longitudinal measurements may lead to biased results. In previous studies these two types of data are frequently analyzed separately where a mixed effects model is used for the longitudinal data and a survival model is applied to the event outcome., Methods: In this paper we compare joint maximum likelihood methods, a two-step approach and a time dependent covariate method that link longitudinal data to survival data with emphasis on using longitudinal measures to predict survival. We apply a Bayesian semi-parametric joint method and maximum likelihood joint method that maximizes the joint likelihood of the time-to-event and longitudinal measures. We also implement the Two-Step approach, which estimates random effects separately, and a classic Time Dependent Covariate Model. We use simulation studies to assess bias, accuracy, and coverage probabilities for the estimates of the link parameter that connects the longitudinal measures to survival times., Results: Simulation results demonstrate that the Two-Step approach performed best at estimating the link parameter when variability in the longitudinal measure is low but is somewhat biased downwards when the variability is high. Bayesian semi-parametric and maximum likelihood joint methods yield higher link parameter estimates with low and high variability in the longitudinal measure. The Time Dependent Covariate method resulted in consistent underestimation of the link parameter. We illustrate these methods using data from the Framingham Heart Study in which lipid measurements and Myocardial Infarction data were collected over a period of 26 years., Conclusions: Traditional methods for modeling longitudinal and survival data, such as the time dependent covariate method, that use the observed longitudinal data, tend to provide downwardly biased estimates. The two-step approach and joint models provide better estimates, although a comparison of these methods may depend on the underlying residual variance.

Aim: This study aimed to analyze the association between any past-month cannabis use and advanced liver fibrosis., Background: Cannabinoid receptors play a role in acute and chronic liver injury, but human studies addressing the impact of cannabis use on liver fibrosis have shown mixed results., Objective: The objective of this study was to explore and estimate the association between pastmonth cannabis use and advanced liver fibrosis (ALF) in a cohort of Russian HIV-positive individuals with heavy alcohol use and a high prevalence of hepatitis C virus (HCV) coinfection., Methods: Baseline data were analyzed from participants of the ZINC study, a trial that enrolled HIV-positive Russian patients without prior antiretroviral therapy. Cannabis use during the prior month was assessed at study entry. ALF was defined as FIB-4>3.25 and APRI>1.5. Transient elastography was used to detect advanced liver fibrosis among participants with FIB-4 values in the intermediate range (between 1.45 and 3.25)., Results: Participants (n=248) were mostly male (72.6%), young (median age of 33.9 years), infected with HCV (87.9%), and did not have advanced immunosuppression (median CD4 count 465). Cannabis use was uncommon (12.4%), and the prevalence of advanced liver disease was 21.7%. The prevalence of ALF was similar among those who used cannabis compared to those who did not (25.8% vs. 21.7%). We were unable to detect an association between cannabis use and ALF (adjusted odds ratio: 1.28, 95% confidence interval: 0.53-3.12, p=0.59) in logistic regression models adjusting for age, sex, heavy drinking, BMI, and CD4 cell count., Conclusion: In this exploratory study among HIV-positive heavy drinking Russians, we did not detect an association between recent cannabis use and ALF. Larger scale studies, including more participants with cannabis use, are needed to examine this relationship further., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Although there is evidence of individual associations between depressive symptoms and hazardous alcohol use with suboptimal antiretroviral therapy (ART) adherence among people living with HIV (PLWH), few studies have established how the two risk factors may interact to predict viral suppression. We conducted secondary data analyses with two cohorts of Ugandan PLWH ( N = 657) to investigate the hypothesized interaction between depressive symptoms (Center for Epidemiological Studies Depression Scale) and hazardous alcohol use (Alcohol Use Disorder Identification Test -Consumption and/or Phosphatidylethanol biomarker) prior to ART initiation with viral suppression (<550 copies/ml). We were unable to detect an interaction between depressive symptoms and hazardous alcohol use prior to ART initiation with viral suppression in the first two years ( M = 19.9 months) after ART initiation ( p = 0.75). There was also no evidence of a main effect association for depressive symptoms (Adjusted Odds Ratio [AOR] = 0.88, 95% Confidence Interval [CI]: 0.50, 1.55) or hazardous alcohol use (AOR = 1.37, 95% CI: 0.80, 2.33). PLWH with depressive symptoms and/or hazardous alcohol use appear to exhibit similar levels of viral suppression as others in care; further work is needed to determine effects on HIV testing and treatment engagement.

Aims: The efficacy of screening and brief intervention for lower-risk drug use is unknown. This pilot study tested the efficacy of two brief interventions (BIs) for drug use compared to no BI in primary care patients with lower-risk drug use identified by screening., Methods: We randomly assigned participants identified by screening with Alcohol Smoking and Substance Involvement Screening Test (ASSIST) drug specific scores of 2 or 3 to: no BI, a brief negotiated interview (BNI), or an adaptation of motivational interviewing (MOTIV). Primary outcome was number of days use of main drug in the past 30 as determined by validated calendar method at 6 months. Analyses were performed using negative binomial regression adjusted for baseline use and main drug., Results: Of 142 eligible adults, 61(43 %) consented and were randomized. Participant characteristics were: mean age 41; 54 % male; 77 % black. Main drug was cannabis 70 %, cocaine 15 %, prescription opioid 10 %; 7% reported injection drug use and mean days use of main drug (of 30) was 3.4. At 6 months, 93 % completed follow-up and adjusted mean days use of main drug were 6.4 (no BI) vs 2.1 (BNI) (incidence rate ratio, IRR 0.33[0.15-0.74]) and 2.3 (MOTIV) (IRR 0.36[0.15-0.85])., Conclusions: BI appears to have efficacy for preventing an increase in drug use in primary care patients with lower-risk use identified by screening. These findings raise the potential that less severe patterns of drug use in primary care may be uniquely amenable to brief intervention and warrant replication., Competing Interests: Declaration of Competing Interest Debbie Cheng serves on Data Safety Monitoring Boards for Janssen Research & Development. The other authors have no conflicts of interest to report., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Addiction Consult Services care for hospitalized patients with substance use disorders (SUD), who frequently utilize costly medical services. This study evaluates whether an addiction consult is associated with 30-day acute care utilization., Methods: This was a retrospective cohort study of 3905 inpatients with SUD. Acute care utilization was defined as any emergency department visit or re-hospitalization within 30 days of discharge. Inverse probability of treatment weighted generalized estimating equations logistic regression models were used to evaluate the relationship between receipt of an addiction consult and 30-day acute care utilization. Exploratory subgroup analyses were performed to describe whether this association differed by type of SUD and discharge on medication for addiction treatment., Results: The 30-day acute care utilization rate was 39.5 % among patients with a consult and 36.0 % among those without. Addiction consults were not significantly associated with care utilization (Adjusted Odds Ratio 1.02; 0.82, 1.28). No significant differences were detected in subgroup analyses; however, the decreased odds among patients with OUD given medication was clinically notable (AOR 0.69; 0.47, 1.02)., Discussion: Repeat acute care utilization is common among hospitalized patients with SUD, particularly those seen by the addiction consult services. While this study did not detect a significant association between addiction consults and 30-day acute care utilization, this relationship merits further evaluation using prospective studies, controlling for key confounders and with a focus on the impact of medications for opioid use disorder., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: HIV, heavy drinking, and smoking are all pro-inflammatory and increase risk for coronary heart disease (CHD). Interventions that reduce alcohol use, smoking, or both in HIV-positive people could lower inflammation, CHD and death risk. Varenicline and cytisine are proven therapies for smoking cessation and may also reduce alcohol consumption. The comparative efficacy of varenicline and cytisine to reduce alcohol consumption has not been tested, nor has their comparative effectiveness been reported for smoking., Objective: This paper describes the protocol of the Studying Partial agonists for Ethanol and Tobacco Elimination in Russians with HIV (St PETER HIV), a four-arm parallel-group randomized controlled trial comparing effects of varenicline, cytisine, and nicotine replacement therapy (NRT)., Methods: The study is recruiting four hundred HIV-positive heavy drinking smokers interested in cutting down on alcohol and/or tobacco in St. Petersburg, Russia. Participants are randomly assigned to receive either active varenicline + NRT placebo, varenicline placebo + active NRT, active cytisine + NRT placebo, cytisine placebo + active NRT. All participants receive evidence-based counseling for alcohol and tobacco use, one active medication, and one placebo. Outcomes are: 1) % heavy drinking days in the past month (primary study outcome at three months) and alcohol craving; 2) cigarettes per day (primary smoking outcome at 3 months) and 7-day point prevalence abstinence and; 3) inflammation, CHD risk, and mortality risk., Conclusion: St PETER HIV addresses the paucity of randomized controlled trial data to guide treatment of alcohol consumption and smoking in HIV-positive heavy drinking smokers., Competing Interests: Dr. Tindle has provided scientific input into the design of a phase III trial for cytisine to be considered for approval by the United States Food and Drug Administration to aid in smoking cessation. In this capacity she has served as an unpaid consultant to Achieve Life Sciences. She is also the principal investigator of an NIH-supported study that has received donated varenicline medication from the manufacturer (Pfizer) for smokers with cancer. The remaining authors report no declarations of interest., (© 2020 Published by Elsevier Inc.)

Background: Tuberculosis (TB) is the leading cause of death among people living with HIV (PLWH), and current evidence suggests that heavy alcohol users have an increased risk of developing TB disease compared to non-drinkers. Not known is whether the increased risk for TB disease among alcohol users may reflect higher rates of latent TB infection (LTBI) among this population. We assessed the latent TB infection prevalence based on tuberculin skin testing (TST) and examined association with current alcohol use among HIV-infected persons on antiretroviral therapy (ART) in south-western Uganda., Methods: We included PLWH at the Mbarara Regional Hospital HIV clinic, who were either current alcohol consumers (prior 3 months) or past year abstainers (2:1 enrolment ratio). Participants were recruited for a study of isoniazid preventive therapy for LTBI. TST was performed using 5 tuberculin units of purified protein derivative. The primary outcome was a positive TST reading (≥5mm induration), reflecting LTBI. We used logistic regression analyses to assess the cross-sectional association between self-reported current alcohol use and a positive TST., Results: Of the 295 of 312 (95%) who returned for TST reading, 63% were females and 63% were current alcohol drinkers. The TST positive prevalence was 27.5% (95% confidence interval [CI]: 22.6% - 32.9%). The odds of a positive TST for current alcohol users compared to abstainers was 0.76 (95% CI: 0.41, 1.41), controlling for gender, age, body mass index, history of smoking, and prior unhealthy alcohol use., Conclusions: The prevalence of LTBI among PLWH on ART in south-western Uganda was moderate and LTBI poses a risk for future infectious TB. Although alcohol use is common, we did not detect an association between current drinking or prior unhealthy alcohol use and LTBI. Further studies to evaluate the association between LTBI and different levels of current drinking (heavy versus not) are needed., Competing Interests: Author DC serves on Data Safety and Monitoring Board for Janssen. The other authors have no conflicts of interest to declare. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Importance: Zinc supplementation can reduce alcohol-related microbial translocation and inflammation., Objective: To assess whether zinc supplementation reduces markers of mortality and risk of cardiovascular disease, reduces levels of inflammation and microbial translocation, and slows HIV disease progression in people with heavy alcohol use who are living with HIV/AIDS., Design, Setting, and Participants: This study is a double-blinded placebo-controlled randomized clinical trial of zinc supplementation among participants recruited from 2013 to 2015. Participants were recruited from HIV and addiction clinical and nonclinical care sites in St Petersburg, Russia. Participants were adults (aged 18-70 years) with documented HIV infection who were antiretroviral therapy-naive at baseline and had past 30-day heavy alcohol consumption. Data analysis was performed from February 2017 to February 2020., Intervention: Pharmacy-grade zinc gluconate supplementation (15 mg for men and 12 mg for women, taken daily by mouth for 18 months) was compared with a placebo., Main Outcomes and Measures: The primary outcome was mortality risk measured as a change in Veterans Aging Cohort Study (VACS) Index score between baseline and 18 months. The VACS Index scores range from 0 to 164, with higher scores indicating higher mortality risk. Secondary outcomes were change in CD4 cell count between baseline and 18 months, the assessment of cardiovascular disease risk (Reynolds Risk Score, which ranges from 0% to 100%, with higher scores indicating higher risk), and changes in inflammatory or microbial translocation biomarkers at 18 months. Adjusted linear regression analyses were performed., Results: A total of 254 participants (184 men [72%]; mean [SD] age, 34 [6] years) were enrolled in the trial; 126 were randomized to receive zinc, and 128 were randomized to receive placebo. Participants had high CD4 cell counts (mean [SD], 521 [292] cells/mm3), and 188 (74%) reported heavy drinking in the past week. In the main analyses, zinc supplementation did not affect changes in the VACS Index score at 18 months (change for zinc, mean [SD], 0.49 [14.6]; median [interquartile range], 0.0 [-7.0 to 6.0]; change for placebo, mean [SD], 5.5 [17.2]; median [interquartile range], 6.0 [-6.0 to 14.0]; adjusted mean difference [AMD], -4.68; 95% CI, -9.62 to 0.25; P = .06) or any secondary outcomes, including change in CD4 cell count (AMD, 41.8 cells/mm3; 95% CI, -20.3 to 103.8 cells/mm3; P = .19), Reynolds Risk Score (AMD, -0.014; 95% CI, -0.167 to 0.139; P = .85), interleukin-6 level (AMD, -0.13 pg/mL; 95% CI, -0.38 to 0.11 pg/mL; P = .30), dimerized plasmin fragment D level (AMD, -0.21 μg/mL fibrinogen equivalent units; 95% CI, -0.48 to 0.07 μg/mL fibrinogen equivalent units; P = .14), soluble CD14 level (AMD, -38.01 ng/mL; 95% CI, -166.90 to 90.88 ng/mL; P = .56), intestinal fatty acid binding protein level (AMD, 0.08 pg/mL; 95% CI, -0.07 to 0.22 pg/mL; P = .32), and lipopolysaccharide binding protein level (AMD, -0.09 ng/mL; 95% CI, -0.23 to 0.06 ng/mL; P = .24). In the per-protocol analyses, zinc supplementation statistically significantly affected changes in the VACS Index score at 18 months (AMD, -7.49; 95% CI, -13.74 to -1.23; P = .02); however, the adherence rate to zinc supplementation was 51%., Conclusions and Relevance: Zinc supplementation did not reduce mortality risk, CD4 cell counts, cardiovascular disease risk, and levels of inflammation or microbial translocation in people with heavy alcohol use who are living with HIV/AIDS. Zinc supplementation did not change the VACS Index score but may have been limited by low adherence., Trial Registration: ClinicalTrials.gov Identifier: NCT01934803.