Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity.

Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61+ tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies.

Long-Acting Injectable ART in Practice: A Mixed Methods Implementation Study Assessing the Feasibility of Using LAI ART in High Risk Populations and At Alternative Low Barrier Care Sites.

Long-acting injectable (LAI) antiretroviral therapy (ART) has the potential to change the lives of people living with HIV (PLWH). To ensure equitable access to new treatment modalities, we examined the feasibility and acceptability of administering Cabotegravir Rilpivirine Long Acting (CAB/RPV LA) to individuals who experience challenging social determinants of health (SDoH) and struggle with adherence to traditional oral ART. Quantitative and qualitative data were used to assess feasibility of utilizing ART at alternative clinic. Data were collected on individuals eligible to receive CAB/RPV LA at an alternative street-based clinic and on individuals receiving CAB/RPV LA at a traditional HIV clinic. After 6 months, participants were interviewed about their experience. Providers involved in the implementation were also interviewed about their experiences. Only one participant (out of 5) who received CAB/RPV LA at the alternative clinic received consistent treatment, whereas 17 out of 18 participants receiving CAB/RPV LA at the traditional clinic site were adherent. Participants and providers believed that LAI had potential for making treatment adherence easier, but identified several barriers, including discrepancies between patients' desires and their lifestyles, impact of LAI on interactions with the medical system, risk of resistance accompanying sub-optimal adherence, and need for a very high level of resources. While LAI has major potential benefits for high-risk patients, these benefits must be balanced with the complexities of implementation. Despite challenges that impacted study outcomes, improving treatment outcomes for PLWH requires addressing SDoH and substance use.

Socioeconomic Status and CD4 Count Among People with HIV Who Inject Drugs in St. Petersburg, Russia.

Lack of access to resources is a "fundamental cause" of poor HIV outcomes across the care cascade globally and may have the greatest impact on groups with co-existing marginalized identities. In a sample of people living with HIV (PWH) who inject drugs and were not on antiretroviral therapy (ART), we explored associations between access to resources and HIV severity. Fundamental Cause Theory (FCT) sees socioeconomic status/access to resources as a root cause of disease and emphasizes that individuals with limited resources have fewer means to mitigate health risks and implement protective behaviors, which ultimately generates disparities in health outcomes. Guided by the FCT, we hypothesized that resource depletion (primary aim) and lower income (secondary aim) were associated with increased HIV severity. Using baseline data from the Linking Infectious and Narcology Care (LINC-II) trial of ART-naive PWH who inject drugs in St. Petersburg, Russia (n = 225), we examined the association between "past year resource runout" (yes vs. no) and "low-income (< 300 USD a month)" and the outcome HIV severity (CD4 count, continuous). We fit two separate linear regression models adjusted for gender, age, time since HIV diagnosis, and prior ART use. Participants had a mean age of 37.5 years and were 60% male. Two thirds (66%) reported resource depletion, and 30% had income below 300 USD a month. Average CD4 count was 416 cells/mm3 (SD 285). No significant association was identified between either resource depletion or low-income and HIV severity (adjusted mean difference in CD4 count for resource depletion: - 4.16, 95% CI - 82.93, 74.62; adjusted mean difference in CD4 count for low-income: 68.13, 95% CI - 15.78, 152.04). Below-average income and running out of resources were common among PWH who inject drugs and are not on ART in St. Petersburg, Russia. Resource depletion and low-income were not significantly associated with HIV disease severity as captured by CD4 count. The nuanced relationship between socioeconomic status and HIV severity among people with HIV who inject drugs and not on ART merits further examination in a larger sample.

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.

Targeted Mass Spectrometry Reveals Interferon-Dependent Eicosanoid and Fatty Acid Alterations in Chronic Myeloid Leukaemia.

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, the detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography-dynamic multiple reaction monitoring-targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of chronic myeloid leukaemia (CML), we found that the levels of intra- and extracellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), extracellular Prostaglandin F2α (PGF2α), extracellular 5-Hydroxyeicosatetraenoic acid (5-HETE), extracellular Palmitic acid (PA, C16:0) and extracellular Stearic acid (SA, C18:0), were altered in response to immunomodulation by type I interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism, with potential relevance in the context of cancer inflammation and CML.

Controlled Electrochemical Barrier Calculations without Potential Control.

The knowledge of electrochemical activation energies under applied potential conditions is a prerequisite for understanding catalytic activity at electrochemical interfaces. Here, we present a new set of methods that can compute electrochemical barriers with accuracy comparable to that of constant potential grand canonical approaches, without the explicit need for a potentiostat. Instead, we Legendre transform a set of constant charge, canonical reaction paths. Additional straightforward approximations offer the possibility to compute electrochemical barriers at a fraction of computational cost and complexity, and the analytical inclusion of geometric response highlights the importance of incorporating electronic as well as the geometric degrees of freedom when evaluating electrochemical barriers.

Characteristics of post-overdose outreach programs and municipal-level opioid overdose in Massachusetts.

BACKGROUND: Post-overdose outreach programs have proliferated in response to opioid overdose. Implementing these programs is associated with reductions in overdose rates, but the role of specific program characteristics in overdose trends has not been evaluated. METHODS: Among 58 Massachusetts municipalities with post-overdose outreach programs, we examined associations between five domains of post-overdose outreach program characteristics (outreach contact rate, naloxone distribution, coercive practices, harm reduction activities, and social service provision or referral) and rates of fatal opioid overdoses and opioid-related emergency medical system responses (i.e., ambulance activations) per calendar quarter from 2013 to 2019 using segmented regression analyses with adjustment for municipal covariates and fixed effects. For both outcomes, each domain was modeled: a) individually, b) with other characteristics, and c) with other characteristics and municipal-level fixed effects. RESULTS: There were no significant associations (p < 0.05) between outreach contact rate, naloxone distribution, coercive practices, or harm reduction activities with municipal fatal overdose trends. Municipalities with programs providing or referring to more social services experienced 21% fewer fatal overdoses compared to programs providing or referring to more social services (Rate Ratio (RR) 0.79, 95% Confidence Interval (CI) 0.66-0.93, p = 0.01). Compared to municipalities in quarters when programs had no outreach contacts, municipalities with some, but less than the median outreach contacts, experienced 14% lower opioid-related emergency responses (RR 0.86, 95% CI 0.78-0.96, p = 0.01). Associations between naloxone distribution, coercive practices, harm reduction practices, or social services and opioid-related emergency responses were not consistently significant across modeling approaches. CONCLUSION: Municipalities with post-overdose outreach programs providing or referring to more social services had lower fatal opioid overdose rates. Municipalities in quarters when programs outreached to overdose survivors had fewer opioid-related emergency responses, but only among programs with below the median number of outreach contacts. Social service linkage should be core to post-overdose programs. Evaluations should assess program characteristics to optimize program design.

Changes to opioid overdose deaths and community naloxone access among Black, Hispanic and White people from 2016 to 2021 with the onset of the COVID-19 pandemic: An interrupted time-series analysis in Massachusetts, USA.

BACKGROUND AND AIMS: The onset of the coronavirus disease 2019 (COVID-19) pandemic was associated with a surge in opioid overdose deaths in Massachusetts, particularly affecting racial and ethnic minority communities. We aimed to compare the impact of the pandemic on opioid overdose fatalities and naloxone distribution from community-based programs across racial and ethnic groups in Massachusetts. DESIGN: Interrupted time-series. SETTING AND CASES: Opioid overdose deaths (OODs) among non-Hispanic White, non-Hispanic Black, Hispanic and non-Hispanic other race people in Massachusetts, USA (January 2016 to June 2021). MEASUREMENTS: Rate of OODs per 100 000 people, rate of naloxone kits distributed per 100 000 people and ratio of naloxone kits per opioid overdose death as a measure of naloxone availability. We applied five imputation strategies using complete data in different periods to account for missingness of race and ethnicity for naloxone data. FINDINGS: Before COVID-19 (January 2016 to February 2020), the rate of OODs declined among non-Hispanic White people [0.2% monthly reduction (95% confidence interval = 0.0-0.4%)], yet was relatively constant among all other population groups. The rate of naloxone kits increased across all groups (0.8-1.2% monthly increase) and the ratio of naloxone kits per OOD death among non-Hispanic White was 1.1% (0.8-1.4%) and among Hispanic people was 1.0% (0.2-1.8%). After the onset of the pandemic (March 2020+), non-Hispanic Black people experienced an immediate increase in the rate of OODs [63.6% (16.4-130%)], whereas rates among other groups remained similar. Trends in naloxone rescue kit distribution did not substantively change among any groups, and the ratio of naloxone kits per OOD death for non-Hispanic Black people did not compensate for the surge in OODs deaths in this group. CONCLUSIONS: With the onset of the COVID-19 pandemic, there was a surge in opioid overdose deaths among non-Hispanic Black people in Massachusetts, USA with no compensatory increase in naloxone rescue kit distribution. For non-Hispanic White and Hispanic people, opioid overdose deaths remained stable and naloxone kit distribution continued to increase.

Strokes in Patients With Injection Drug Use and Tricuspid Valve Endocarditis - A Case Series.

Research Design: In this study, we describe patients from a tertiary care safety-net hospital endocarditis registry with tricuspid valve infective endocarditis (TVIE), and concomitant acute or subacute ischemic stroke predominantly associated with injection drug use (IDU). We retrospectively obtained data pertinent to neurologic examinations, history of injection drug use (IDU), blood cultures, transthoracic/transesophageal echocardiography (TTE/TEE), neuroimaging, and Modified Rankin Scale (mRS) scores at discharge. Only those patients with bacteremia, tricuspid valve vegetations, and neuroimaging consistent with acute to subacute ischemic infarction and microhemorrhages in two cases were included in this series. Results: Of 188 patients in the registry, 66 patients had TVIE and 10 of these were complicated by ischemic stroke. Neurologic symptoms were largely non-specific, eight patients had altered mental status and only 3 had focal deficits. Nine cases were associated with IDU. Two patients had evidence of a patent foramen ovale on echocardiography. Blood cultures grew S. aureus species in 9 of the patients, all associated with IDU. Three patients died during hospitalization. The mRS score at discharge for survivors ranged 0-4. Conclusions: Patients with strokes from TVIE had heterogeneous presentations and putative mechanisms. We noted that robust neuroimaging is lacking for patients with TVIE from IDU and that such patients may benefit from neuroimaging as a screen for strokes to assist peri-operative management. Further inquiry is needed to elucidate stroke mechanisms in these patients.

Perspectives and recommendations of opioid overdose survivors experiencing unsheltered homelessness on housing, overdose, and substance use treatment in Boston, MA.

INTRODUCTION: Opioid overdose causes one in four deaths among people experiencing homelessness in Boston, MA. To reduce overdose risks, the experience and perspectives of people experiencing homelessness should be incorporated into housing, overdose prevention, and substance use treatment efforts. METHODS: In 2021, we conducted qualitative interviews with 59 opioid overdose survivors to inform equitable access to treatment services. In response to policy debate surrounding a public drug scene near a key recruitment site, we conducted a targeted thematic analysis of transcribed interview data from a subset of participants experiencing unsheltered homelessness (n=29) to explore their perspectives and recommendations on housing, overdose prevention, and substance use treatment. RESULTS: Among 29 participants who identified as non-Hispanic Black (n=10), Hispanic/Latinx (n=10), or as non-Hispanic White (n=9), the median number of self-reported opioid overdoses in the past three months was 2.0 (SD 3.7). Three themes emerged from this targeted analysis: (1) Participants described inadequate housing resources and unwelcoming shelter environments. (2) Participants near a large public drug scene explained how unsheltered homelessness was chaotic, dangerous, and disruptive to recovery goals. (3) Participants provided recommendations for improving housing and addiction treatment systems and including their perspectives in the development of solutions to the intersecting housing and opioid overdose crises. CONCLUSIONS: The overdose prevention, housing and substance use treatment systems must address the needs of opioid overdose survivors experiencing unsheltered homelessness. Overdose survivors experiencing unsheltered homelessness described a chaotic public drug scene but resorted to residing in nearby encampments because the existing shelter, housing, and addiction treatment systems were unwelcoming, difficult to navigate, or unaffordable. Despite efforts to provide low-threshold housing in Boston, additional low-barrier housing services (i.e., including harm reduction resources and without "sobriety" requirements) could promote the health and safety of people who use drugs and are experiencing homelessness.

Estimated Clinical Outcomes and Cost-effectiveness Associated With Provision of Addiction Treatment in US Primary Care Clinics.

Importance: US primary care practitioners (PCPs) are the largest clinical workforce, but few provide addiction care. Primary care is a practical place to expand addiction services, including buprenorphine and harm reduction kits, yet the clinical outcomes and health care sector costs are unknown. Objective: To estimate the long-term clinical outcomes, costs, and cost-effectiveness of integrated buprenorphine and harm reduction kits in primary care for people who inject opioids. Design, Setting, and Participants: In this modeling study, the Reducing Infections Related to Drug Use Cost-Effectiveness (REDUCE) microsimulation model, which tracks serious injection-related infections, overdose, hospitalization, and death, was used to examine the following treatment strategies: (1) PCP services with external referral to addiction care (status quo), (2) PCP services plus onsite buprenorphine prescribing with referral to offsite harm reduction kits (BUP), and (3) PCP services plus onsite buprenorphine prescribing and harm reduction kits (BUP plus HR). Model inputs were derived from clinical trials and observational cohorts, and costs were discounted annually at 3%. The cost-effectiveness was evaluated over a lifetime from the modified health care sector perspective, and sensitivity analyses were performed to address uncertainty. Model simulation began January 1, 2021, and ran for the entire lifetime of the cohort. Main Outcomes and Measures: Life-years (LYs), hospitalizations, mortality from sequelae (overdose, severe skin and soft tissue infections, and endocarditis), costs, and incremental cost-effectiveness ratios (ICERs). Results: The simulated cohort included 2.25 million people and reflected the age and gender of US persons who inject opioids. Status quo resulted in 6.56 discounted LYs at a discounted cost of $203 500 per person (95% credible interval, $203 000-$222 000). Each strategy extended discounted life expectancy: BUP by 0.16 years and BUP plus HR by 0.17 years. Compared with status quo, BUP plus HR reduced sequelae-related mortality by 33%. The mean discounted lifetime cost per person of BUP and BUP plus HR were more than that of the status quo strategy. The dominating strategy was BUP plus HR. Compared with status quo, BUP plus HR was cost-effective (ICER, $34 400 per LY). During a 5-year time horizon, BUP plus HR cost an individual PCP practice approximately $13 000. Conclusions and Relevance: This modeling study of integrated addiction service in primary care found improved clinical outcomes and modestly increased costs. The integration of addiction service into primary care practices should be a health care system priority.

Association of Implementation of Postoverdose Outreach Programs With Subsequent Opioid Overdose Deaths Among Massachusetts Municipalities.

Importance: Nonfatal opioid overdose is the leading risk factor for subsequent fatal overdose and represents a critical opportunity to reduce future overdose and mortality. Postoverdose outreach programs emerged in Massachusetts beginning in 2013 with the main purpose of linking opioid overdose survivors to addiction treatment and harm reduction services. Objective: To evaluate whether the implementation of postoverdose outreach programs among Massachusetts municipalities was associated with lower opioid fatality rates compared with municipalities without postoverdose outreach programs. Design, Setting, and Participants: This retrospective interrupted time-series analysis was performed over 26 quarters (from January 1, 2013, through June 30, 2019) across 93 municipalities in Massachusetts. These 93 municipalities were selected based on a threshold of 30 or more opioid-related emergency medical services (EMS) responses in 2015. Data were analyzed from November 2021 to August 2022. Exposures: The main exposure was municipality postoverdose outreach programs. Municipalities had various program inceptions during the study period. Main Outcomes and Measures: The primary outcome was quarterly municipal opioid fatality rate per 100 000 population. The secondary outcome was quarterly municipal opioid-related EMS response (ambulance trips) rates per 100 000 population. Results: The mean (SD) population size across 93 municipalities was 47 622 (70 307), the mean (SD) proportion of female individuals was 51.5% (1.5%) and male individuals was 48.5% (1.5%), and the mean (SD) age proportions were 29.7% (4.0%) younger than 25 years, 26.0% (4.8%) aged 25 to 44 years, 14.8% (2.1%) aged 45 to 54 years, 13.4% (2.1%) aged 55 to 64 years, and 16.1% (4.4%) aged 65 years or older. Postoverdose programs were implemented in 58 municipalities (62%). Following implementation, there were no significant level changes in opioid fatality rate (adjusted rate ratio [aRR], 1.07; 95% CI, 0.96-1.19; P = .20). However, there was a significant slope decrease in opioid fatality rate (annualized aRR, 0.94; 95% CI, 0.90-0.98; P = .003) compared with the municipalities without the outreach programs. Similarly, there was a significant slope decrease in opioid-related EMS response rates (annualized aRR, 0.93; 95% CI, 0.89-0.98; P = .007). Several sensitivity analyses yielded similar findings. Conclusions and Relevance: In this study, among Massachusetts municipalities with high numbers of opioid-related EMS responses, implementation of postoverdose outreach programs was significantly associated with lower opioid fatality rates over time compared with municipalities that did not implement such programs. Program components, including cross-sectoral partnerships, operational best practices, involvement of law enforcement, and related program costs, warrant further evaluation to enhance effectiveness.

Association of Early Opioid Withdrawal Treatment Strategy and Patient-Directed Discharge Among Hospitalized Patients with Opioid Use Disorder.

BACKGROUND: Medical hospitalizations for people with opioid use disorder (OUD) frequently result in patient-directed discharges (PDD), often due to untreated pain and withdrawal. OBJECTIVE: To investigate the association between early opioid withdrawal management strategies and PDD. DESIGN: Retrospective cohort study using three datasets representing 362 US hospitals. PARTICIPANTS: Adult patients hospitalized between 2009 and 2015 with OUD (as identified using ICD-9-CM codes or inpatient buprenorphine administration) and no PDD on the day of admission. INTERVENTIONS: Opioid withdrawal management strategies were classified based on day-of-admission receipt of any of the following treatments: (1) medications for OUD (MOUD) including methadone or buprenorphine, (2) other opioid analgesics, (3) adjunctive symptomatic medications without opioids (e.g., clonidine), and (4) no withdrawal treatment. MAIN MEASURES: PDD was assessed as the main outcome and hospital length of stay as a secondary outcome. KEY RESULTS: Of 6,715,286 hospitalizations, 127,158 (1.9%) patients had OUD and no PDD on the day of admission, of whom 7166 (5.6%) had a later PDD and 91,051 (71.6%) patients received some early opioid withdrawal treatment (22.3% MOUD; 43.4% opioid analgesics; 5.9% adjunctive medications). Compared to no withdrawal treatment, MOUD was associated with a lower risk of PDD (adjusted odds ratio [aOR] = 0.73, 95%CI 0.68-0.8, p < .001), adjunctive treatment alone was associated with higher risk (aOR = 1.13, 95%CI: 1.01-1.26, p = .031), and treatment with opioid analgesics alone was associated with similar risk (aOR 0.95, 95%CI: 0.89-1.02, p = .148). Among those with PDD, both MOUD (adjusted incidence rate ratio [aIRR] = 1.24, 95%CI: 1.17-1.3, p < .001) and opioid analgesic treatments (aIRR = 1.39, 95%CI: 1.34-1.45, p < .001) were associated with longer hospital stays. CONCLUSIONS: MOUD was associated with decreased risk of PDD but was utilized in < 1 in 4 patients. Efforts are needed to ensure all patients with OUD have access to effective opioid withdrawal management to improve the likelihood they receive recommended hospital care.

Fluid Flow Templating of Polymeric Soft Matter with Diverse Morphologies.

It is challenging to find a conventional nanofabrication technique that can consistently produce soft polymeric matter of high surface area and nanoscale morphology in a way that is scalable, versatile, and easily tunable. Here, the capabilities of a universal method for fabricating diverse nano- and micro-scale morphologies based on polymer precipitation templated by the fluid streamlines in multiphasic flow are explored. It is shown that while the procedure is operationally simple, various combinations of its intertwined mechanisms can controllably and reproducibly lead to the formation of an extraordinary wide range of colloidal morphologies. By systematically investigating the process conditions, 12 distinct classes of polymer micro- and nano-structures including particles, rods, ribbons, nanosheets, and soft dendritic colloids (dendricolloids) are identified. The outcomes are interpreted by delineating the physical processes into three stages: hydrodynamic shear, capillary and mechanical breakup, and polymer precipitation rate. The insights into the underlying fundamental mechanisms provide guidance toward developing a versatile and scalable nanofabrication platform. It is verified that the liquid shear-based technique is versatile and works well with many chemically diverse polymers and biopolymers, showing potential as a universal tool for simple and scalable nanofabrication of many morphologically distinct soft matter classes.

Perspectives on long-acting injectable HIV antiretroviral therapy at an alternative care site: a qualitative study of people with HIV experiencing substance use and/or housing instability.

INTRODUCTION: Adherence to daily oral antiretroviral therapy (ART) and regular clinic appointments can be challenging for individuals who experience adverse social determinants of health. Long-acting injectable ART administered outside of traditional clinic settings may be a promising solution to adherence barriers, but additional research is needed to assess patients' perspectives. This study assessed perspectives of people living with HIV (PLWH) who had difficulty with adherence to traditional HIV care models and evaluated feasibility and acceptability of receiving a long-acting ART injection at a location outside of a traditional HIV clinic to address barriers to HIV care. METHODS: Qualitative interviews (n = 26) were conducted with PLWH who had experienced barriers to adherence. Participants were referred to the study by staff from Project Trust, a drop in harm reduction and sexually transmitted infection/HIV clinic. The interviews were conducted between May and November 2021. Interviews were recorded, professionally transcribed, coded, and analyzed qualitatively using the integrated-Promoting Action on Research Implementation in Health Services framework. RESULTS: We identified 6 main themes regarding the acceptability of receiving a long-acting injection to treat HIV, and the acceptability and feasibility of receiving injections at an alternative care site. Participants specified that they: (1) have a general understanding about their HIV care and the importance of ART adherence, (2) prefer a long-acting injection over a daily pill regimen, (3) expressed concerns about injection safety and efficacy, (4) had specific logistical aspects around the delivery of long-acting injections, including location of injection administration, that they believed would improve their ability to adhere, (5) have confidence that they can become undetectable and then complete the oral lead-in required to begin receiving the injection, and (6) see potential barriers that remain a concern for successful adherence to long-acting injections. CONCLUSION: To better treat HIV among people who are living with challenging social determinants of health, interventions that include a long-acting injection in a non-traditional care setting may prove to be a promising treatment option.

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.

Effect of police action on low-barrier substance use disorder service utilization.

BACKGROUND: Police action can increase risky substance use patterns by people who use drugs (PWUD), but it is not known how increased police presence affects utilization of low-barrier substance use disorder bridge clinics. Increased police presence may increase or decrease treatment-seeking behavior. We examined the association between Operation Clean Sweep (OCS), a 2-week police action in Boston, MA, and visit volume in BMC's low-barrier buprenorphine bridge clinic. METHODS: In this retrospective cohort, we used segmented regression to investigate whether the increased police presence during OCS was associated with changes in bridge clinic visits. We used General Internal Medicine (GIM) clinic visit volume as a negative control. We examined visits during the 6 weeks prior, 2 weeks during, and 4 weeks after OCS (June 18-September 11, 2019). RESULTS: Bridge clinic visits were 2.8 per provider session before, 2.0 during, and 3.0 after OCS. The mean number of GIM clinic visits per provider session before OCS was 7.0, 6.8 during, and 7.0 after OCS. In adjusted segmented regression models for bridge clinic visits per provider session, there was a nonsignificant level increase (0.643 P = 0.171) and significant decrease in slope (0.100, P = 0.045) during OCS. After OCS completed, there was a significant level increase (1.442, P = 0.003) and slope increase in visits per provider session (0.141, P = 0.007). There was no significant change in GIM clinic volume during the study period. CONCLUSIONS: The increased policing during OCS was associated with a significant decrease in bridge clinic visits. Following the completion of OCS, there was a significant increase in clinic visits, suggesting pent-up demand for medications for opioid use disorder, a life-saving treatment.