Community-Based Cluster-Randomized Trial to Reduce Opioid Overdose Deaths.

BACKGROUND: Evidence-based practices for reducing opioid-related overdose deaths include overdose education and naloxone distribution, the use of medications for the treatment of opioid use disorder, and prescription opioid safety. Data are needed on the effectiveness of a community-engaged intervention to reduce opioid-related overdose deaths through enhanced uptake of these practices. METHODS: In this community-level, cluster-randomized trial, we randomly assigned 67 communities in Kentucky, Massachusetts, New York, and Ohio to receive the intervention (34 communities) or a wait-list control (33 communities), stratified according to state. The trial was conducted within the context of both the coronavirus disease 2019 (Covid-19) pandemic and a national surge in the number of fentanyl-related overdose deaths. The trial groups were balanced within states according to urban or rural classification, previous overdose rate, and community population. The primary outcome was the number of opioid-related overdose deaths among community adults. RESULTS: During the comparison period from July 2021 through June 2022, the population-averaged rates of opioid-related overdose deaths were similar in the intervention group and the control group (47.2 deaths per 100,000 population vs. 51.7 per 100,000 population), for an adjusted rate ratio of 0.91 (95% confidence interval, 0.76 to 1.09; P = 0.30). The effect of the intervention on the rate of opioid-related overdose deaths did not differ appreciably according to state, urban or rural category, age, sex, or race or ethnic group. Intervention communities implemented 615 evidence-based practice strategies from the 806 strategies selected by communities (254 involving overdose education and naloxone distribution, 256 involving the use of medications for opioid use disorder, and 105 involving prescription opioid safety). Of these evidence-based practice strategies, only 235 (38%) had been initiated by the start of the comparison year. CONCLUSIONS: In this 12-month multimodal intervention trial involving community coalitions in the deployment of evidence-based practices to reduce opioid overdose deaths, death rates were similar in the intervention group and the control group in the context of the Covid-19 pandemic and the fentanyl-related overdose epidemic. (Funded by the National Institutes of Health; HCS ClinicalTrials.gov number, NCT04111939.).

Pilot RCT comparing low-dose naltrexone, gabapentin and placebo to reduce pain among people with HIV with alcohol problems.

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).

Impact of the Communities That HEAL Intervention on Buprenorphine-Waivered Practitioners and Buprenorphine Prescribing: A Prespecified Secondary Analysis of the HCS Randomized Clinical Trial.

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.

Healthcare Utilization Among Persons with HIV and Unhealthy Alcohol Use in St. Petersburg, Russia.

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.

The Relationship between Age at Initiation of Regular Drinking of Alcohol and Viral Suppression Status, and Depression Symptoms Among People Living with HIV in South-Western Uganda.

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.

Stigma and other correlates of sharing injection equipment among people with HIV in St. Petersburg, Russia.

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.

State same-sex marriage policies and pre-exposure prophylaxis implementation among men who have sex with men in the United States.

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.

Rapid access to antiretroviral therapy, receipt of naltrexone, and strengths-based case management versus standard of care for HIV viral load suppression in people with HIV who inject drugs in Russia (LINC-II): an open-label, randomised controlled trial.

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.

Provider-patient experiences and HIV care utilization among people living with HIV who inject drugs in St. Petersburg, Russia.

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.

Safety and tolerability of isoniazid preventive therapy for tuberculosis for persons with HIV with and without alcohol use.

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).

Food Insecurity and Transmission Risks Among People with HIV Who Use Substances.

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.

RESUMEN: La inseguridad alimentaria (IF) afecta a las personas que viven con VIH (PVV y a personas con abuso desustancias (.ej. drogas y alcohol). Evaluamos la asociación longitudinal entre la IF y los riesgos de transmisión del VIH (relaciones sexuales sin protección y agujas/jeringas compartidas). Entre 351 PVVcon abuso de sustancias en Rusia, el 51,6% reportó FI y el 37,0% consumió drogas intravenosas en el último mes. El promedio de contactos sexuales sin protección en los últimos 90 días fue de 13,4 (DE 30,1); el 9,7% informó haber compartido agujas/jeringas en el último mes. No encontramos una asociación significativa entre IF leve/moderada (IRR ajustada = 0,87, IC 95% = 0,47, 1,61) o IF grave (IRRa = 0,84, IC 95% = 0,46, 1,54; p global = 0,85) y relaciones sexuales sin protección. Observamos una asociación significativa entre IF grave y compartir agujas/jeringas en el último mes (OR ajustado = 3,27, IC 95% = 1,45, 7,39; p = 0,004), pero no entre IF leve/moderada y compartir agujas/jeringas en el último mes (ORa = 1,40, IC 95% = 0,58, 3,38; p = 0,45). Estos hallazgos sugieren que la IF grave podría ser un enfoque para intervenciones que buscan reducir la transmisión del VIH.

Pilot study of tolerability and safety of opioid receptor antagonists as novel therapies for chronic pain among persons living with HIV with past year heavy drinking: a randomized controlled trial.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03278886.

Bar Attendance and Alcohol Use Before and After COVID-19 Related Restrictions Among HIV-infected Adults in South-Western Uganda.

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.

Incarceration history, antiretroviral therapy, and stigma: A cross-sectional study of people with HIV who inject drugs in St. Petersburg, Russia.

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.

Performance of model-based vs. permutation tests in the HEALing (Helping to End Addiction Long-termSM) Communities Study, a covariate-constrained cluster randomized trial.

BACKGROUND: The HEALing (Helping to End Addiction Long-termSM) 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.

Unhealthy Alcohol Use Is Associated With Suboptimal Adherence to Isoniazid Preventive Therapy in Persons With HIV in Southwestern Uganda.

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.

Effectiveness of Varenicline and Cytisine for Alcohol Use Reduction Among People With HIV and Substance Use: A Randomized Clinical Trial.

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.

Impulsivity and linkage to HIV Care among People living with HIV in St. Petersburg, Russia.

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.

A collaborative care intervention to improve opioid prescribing among providers caring for persons with HIV: Impact on satisfaction, confidence, and trust.

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.

Exploring the Association Between Social Support and Hazardous Alcohol Use Among Persons Living with HIV in South Western Uganda.

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.