"Harm reduction approach for tuberculosis and substance use disorders: A review of approaches and implications in the Indian context".

There are limitations to traditional treatment approaches in addressing the needs of individuals with dual comorbidity of TB and SUD. The concept of harm reduction as a distinct approach to addressing substance use, focusing on minimising the negative consequences associated with it rather than advocating for complete abstinence. Different harm reduction strategies, such as opioid substitution therapy, needle and syringe programmes, testing for viral infections etc. have been effectively employed for SUDs in past. Similarly, TB risk minimization approaches like improving housing and nutrition and focused testing strategies are considered as harm reduction strategies for TB management. The relationship between tuberculosis (TB) and substance use disorders (SUDs) involves a complex interplay of biopsychosocial factors. It is crucial to prioritise integrated and closely monitored care in order to address the treatment challenges and potential drug interactions that may arise. In light of the acknowledged challenges like limited awareness, infrastructure, drug resistance, and stigma, it is imperative to explore potential avenues for the implementation of harm reduction strategies targeting individuals with comorbid TB and SUD in India. Potential strategies for addressing the issue includes a range of measures, such as augmenting investments in healthcare, integrating policies, tackling social determinants, and establishing shared platforms for psychosocial rehabilitation.

Injection network drivers of HIV prevention service utilization among people who inject drugs: results of a community-based sociometric network cohort in New Delhi, India.

INTRODUCTION: Injection drug networks may influence their network members' health-seeking behaviours. Using data from a sociometric injecting partner network of people who inject drugs (PWID) in New Delhi, India, we assessed the role of injecting partner (alter) behaviours on individual engagement in HIV prevention services. METHODS: We enumerated injecting partner linkages among 2512 PWID using coupon referrals and biometric data from November 2017 to March 2020. Participants completed interviewer-administered questionnaires and provided information on injection behaviours, injecting partners, HIV/hepatitis C (HCV) testing and service engagement. Multilevel multiple-membership models (MMMM) evaluated individual PWID HIV testing, medication for opioid use disorder (MOUD) and syringe service engagement as a function of alter attributes, accounting for membership across multiple ego-networks. Logistic regression models assessed parallel associations among socially proximal injecting peers, defined as PWID ≤3 path length from ego. RESULTS: Median age was 26 years; 99% were male. PWID had median 2 injecting partners and 8 socially proximal peers; 14% reported HIV testing, 33% accessed MOUD and 13% used syringe services 6 months prior. In MMMM analyses, PWID with ≥1 versus 0 injecting partners who received HIV testing were significantly more likely to report HIV testing (adjusted odds ratio [aOR]: 2.27, 95% confidence interval [CI]: 1.68-3.16), MOUD (aOR: 1.99, 95% CI: 1.60-2.53) and syringe service use (aOR: 1.66, 95% CI: 1.21-2.39). We observed similar findings for individual MOUD and syringe service use. Having ≥1 versus 0 HIV-positive partners was associated with decreased HIV testing and MOUD but increased syringe service use (aOR: 1.54, 95% CI: 1.09-2.17). PWID with ≥1 versus 0 socially proximal peers who used non-sterile injection equipment reported increased HIV testing (aOR: 1.39, 95% CI: 1.01-1.92), MOUD (aOR: 1.40, 95% CI: 1.10-1.77) and syringe service use (aOR: 1.82, 95% CI: 1.23-2.68). CONCLUSIONS: We found differential associative relationships between individual HIV prevention service engagement and the health or risk behaviours of direct and indirect alters. Characterizing network exposure beyond direct injecting partnerships provided important context on possible mechanisms of behavioural influence. Findings could be leveraged to design peer-based interventions that promote network diffusion of health-seeking behaviours.

Hospitalization is a missed opportunity for HIV screening, pre-exposure prophylaxis, and treatment.

BACKGROUND: Hospitalization is a "reachable moment" for people who inject drugs (PWID), but preventive care including HIV testing, prevention and treatment is rarely offered within inpatient settings. METHODS: We conducted a multisite, retrospective cohort study of patients with opioid use disorder with infectious complications of injection drug use hospitalized between 1/1/2018-12/31/2018. We evaluated HIV care continuum outcomes using descriptive statistics and hypothesis tests for intergroup differences. RESULTS: 322 patients were included. Of 300 patients without known HIV, only 2 had a documented discussion of PrEP, while only 1 was prescribed PrEP on discharge. Among the 22 people with HIV (PWH), only 13 (59%) had a viral load collected during admission of whom all were viremic and 10 (45%) were successfully linked to care post-discharge. Rates of readmission, Medicaid or uninsured status, and unstable housing were high in both groups. DISCUSSION: We observed poor provision of HIV testing, PrEP and other HIV services for hospitalized PWID across multiple U.S. medical centers. Future initiatives should focus on providing this group with comprehensive HIV testing and treatment services through a status neutral approach.

HTLV in Sweden.

Sweden is a country with a low prevalence of human lymphotropic T-cell virus (HTLV) infection, estimated at < 0.005%, but the infection rate is notably higher in specific risk groups such as HTLV-2 among intravenous drug users (IVDU) and people originating from HTLV-1 highly endemic areas. Thus, in the most recent study from 2012, the prevalence of HTLV-2 among IVDU in Stockholm was 3.2%. However, much of the epidemiological data on HTLV in Sweden stems from studies conducted primarily between the 1990s and 2007, and the impact of migration to Sweden during the past 15 years has not been evaluated. Despite Sweden's status as a country with generally low prevalence of HTLV, it is prudent to anticipate and prepare for several potential challenges associated with HTLV infection in the future. Proactive measures to enhance awareness, alongside strategies to curtail transmission and mitigate complications, are crucial for addressing this relatively rare, but significant health issue. In this work, we review the current epidemiological knowledge about HTLV in Sweden and discuss future Swedish perspectives.

Integration of Hepatitis C and Addiction Treatment in People Who Inject Drugs: The San Patrignano HCV-Free and Drug-Free Experience.

Injection drug use represents an important contributor to hepatitis C virus (HCV) transmission, hence therapeutic communities (TCs) are promising points of care for the identification and treatment of HCV-infected persons who inject drugs (PWIDs). We evaluated the effectiveness and efficacy of an HCV micro-elimination program targeting PWIDs in the context of a drug-free TC; we applied the cascade of care (CoC) evaluation by calculating frequencies of infection diagnosis, confirmation, treatment and achievement of a sustained virological response (SVR). We also evaluated the risk of reinfection of PWIDs achieving HCV eradication by collecting follow-up virologic information of previously recovered individuals and eventual relapse in drug use, assuming the latter as a potential source of reinfection. We considered 811 PWIDs (aged 18+ years) residing in San Patrignano TC at the beginning of the observation period (January 2018-March 2022) or admitted thereafter, assessing for HCV and HIV serology and viral load by standard laboratory procedures. Ongoing infections were treated with direct-acting antivirals (DAA), according to the current national guidelines. Out of the 792 individuals tested on admission, 503 (63.5%) were found to be seropositive for antibodies against HCV. A total of 481 of these 503 individuals (95.6%) underwent HCV RNA testing. Out of the 331 participants positive for HCV RNA, 225 were ultimately prescribed a DAA treatment with a sustained viral response (SVR), which was achieved by 222 PWIDs (98.7%). Of the 222 PWIDs, 186 (83.8%) with SVR remained HCV-free on follow-up (with a median follow-up of 2.73 years after SVR ascertainment). The CoC model in our TC proved efficient in implementing HCV micro-elimination, as well as in preventing reinfection and promoting retention in the care of individuals, which aligns with the therapeutic goals of addiction treatment.

Project CHARIOT: study protocol for a hybrid type 1 effectiveness-implementation study of comprehensive tele-harm reduction for engagement of people who inject drugs in HIV prevention services.

BACKGROUND: People who inject drugs (PWID) remain a high priority population under the federal Ending the HIV Epidemic initiative with 11% of new HIV infections attributable to injection drug use. There is a critical need for innovative, efficacious, scalable, and community-driven models of healthcare in non-stigmatizing settings for PWID. We seek to test a Comprehensive-TeleHarm Reduction (C-THR) intervention for HIV prevention services delivered via a syringe services program (SSP). METHODS: The CHARIOT trial is a hybrid type I effectiveness-implementation study using a parallel two-arm randomized controlled trial design. Participants (i.e., PWID; n = 350) will be recruited from a syringe services program (SSP) in Miami, Florida. Participants will be randomized to receive either C-THR or non-SSP clinic referral and patient navigation. The objectives are: (1) to determine if the C-THR intervention increases engagement in HIV prevention (i.e., HIV pre-exposure prophylaxis; PrEP or medications for opioid use disorder; MOUD) compared to non-SSP clinic referral and patient navigation, (2) to examine the long-term effectiveness and cost-effectiveness of the C-THR intervention, and (3) to assess the barriers and facilitators to implementation and sustainment of the C-THR intervention. The co-primary outcomes are PrEP or MOUD engagement across follow-up at 3, 6, 9 and 12 months. For PrEP, engagement is confirmed by tenofovir on dried blood spot or cabotegravir injection within the previous 8 weeks. For MOUD, engagement is defined as screening positive for norbuprenorphine or methadone on urine drug screen; or naltrexone or buprenorphine injection within the previous 4 weeks. Secondary outcomes include PrEP adherence, engagement in HCV treatment and sustained virologic response, and treatment of sexually transmitted infections. The short and long term cost-effectiveness analyses and mixed-methods implementation evaluation will provide compelling data on the sustainability and possible impact of C-THR on comprehensive HIV prevention delivered via SSPs. DISCUSSION: The CHARIOT trial will be the first to our knowledge to test the efficacy of an innovative, peer-led telehealth intervention with PWID at risk for HIV delivered via an SSP. This innovative healthcare model seeks to transform the way PWID access care by bypassing the traditional healthcare system, reducing multi-level barriers to care, and meeting PWID where they are. TRIAL REGISTRATION: ClinicalTrials.gov NCT05897099. Trial registry name: Comprehensive HIV and Harm Prevention Via Telehealth (CHARIOT). Registration date: 06/12/2023.

Unmet need for medication for opioid use disorder among persons who inject drugs in 23 U.S. cities.

BACKGROUND: Persons who inject drugs (PWID) are at increased risk of HIV and hepatitis C virus (HCV) infections and premature mortality due to drug overdose. Medication for opioid use disorder (MOUD), such as methadone or buprenorphine, reduces injecting behaviors, HIV and HCV transmission, and mortality from opioid overdose. Using data from National HIV Behavioral Surveillance, we evaluated the unmet need for MOUD among PWID in 23 U.S. cities. METHODS: PWID were recruited by respondent-driven sampling, interviewed, and tested for HIV. This analysis includes PWID who were ≥18 years old and reported injecting drugs and opioid use in the past 12 months. We used Poisson regression to examine factors associated with self-reported unmet need for MOUD and reported adjusted prevalence ratios (aPR) with 95% confidence intervals. RESULTS: Of 10,879 PWID reporting using opioids, 68.8% were male, 48.2% were ≥45 years of age, 38.8% were non-Hispanic White, 49.6% experienced homelessness, and 28.0% reported an unmet need for MOUD in the past 12 months. PWID who were more likely to report unmet need for MOUD experienced homelessness (aPR 1.26; 95% CI: 1.19-1.34), were incarcerated in the past 12 months (aPR 1.15; 95% CI: 1.08-1.23), injected ≥once a day (aPR 1.42; 95% CI: 1.31-1.55), reported overdose (aPR 1.33; 95% CI: 1.24-1.42), and sharing of syringes (aPR 1.14; 95% CI: 1.06-1.23). CONCLUSIONS: The expansion of MOUD provision for PWID is critical. Integrating syringe service programs and MOUD provision and linking PWID who experience overdose, incarceration or homelessness to treatment with MOUD could improve its utilization among PWID.

The burden of skin and soft tissue, bone and joint infections in an Australian cohort of people who inject drugs.

INTRODUCTION: There are currently limited data regarding the clinical and economic significance of skin and soft tissue infections (SSTI) and bone and joint infections in Australian people who inject drugs (PWID). METHODS: Retrospective cohort study in adult PWID admitted to Monash Health, a large heath care network with six hospitals in Victoria, Australia. Inpatients were identified using administrative datasets and International Classification of Disease (ICD-10) coding for specific infection-related conditions. Cost analysis was based on mean ward, intensive care and hospital-in-the-home (HITH) lengths of stay. Spinal infections and endocarditis were excluded as part of previous studies. RESULTS: A total of 185 PWID (61 female, 124 male, median age 37) meeting the study criteria were admitted to Monash Health between January 2010 and January 2021. Admitting diagnoses included 78 skin abscesses, 80 cellulitis, 17 septic arthritis, 4 osteomyelitis, 3 thrombophlebitis and 1 each of necrotising fasciitis, vasculitis and myositis. Pain (87.5%) and swelling (75.1%) were the most common presenting complaints. Opioids (67.4%) and methamphetamine (37.5%) were the most common primary drugs injected. Almost half (46.5%) of patients had concurrent active hepatitis C (HCV) infection on admission. Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) were uncommon. The most significant causative organism was methicillin-susceptible Staphylococcus aureus (24.9%). In 40.0% (74/185) no organism was identified. Patients required a median acute hospital stay of 5 days (2-51 days). There were 15 patients admitted to the intensive care unit (ICU) with median duration 2 days. PICC line insertion for antibiotics was required in 16.8% of patients, while 51.4% required surgical intervention. Median duration of both oral and IV antibiotic therapy was 11 days. Almost half (48.6%) of patients were enrolled in an opioid maintenance program on discharge. Average estimated expenditure was AUD $16, 528 per admission. CONCLUSION: Skin and soft tissue and joint infections are a major cause of morbidity for PWID. Admission to hospital provides opportunistic involvement of addiction specialty services.

Integrating methadone into primary care settings in Ukraine: effects on provider stigma and knowledge.

INTRODUCTION: Stigma has undermined the scale-up of evidence-based HIV prevention and treatment. Negative beliefs influence clinicians' discriminatory behaviour and ultimately have wide-ranging effects across the HIV prevention and treatment continuum. Stigma among clinicians can be mitigated in several ways, including through interpersonal contact. In this study, we test whether interactions with people who inject drugs (PWID) influence attitudes of both direct and indirect providers of opioid agonist therapies (OATs) within the same primary care clinics (PCCs) where OAT is newly introduced. METHODS: In a cluster randomized controlled trial integrating OAT and HIV care into PCCs in Ukraine, clinicians at 24 integrated care sites (two sites in 12 regions) from January 2018 to August 2022 completed a structured survey at baseline, 12 and 24 months. The survey included feeling thermometers and standardized scales related to clinician attitudes towards patients and evidence-based care. Nested linear mixed-effects models were used to examine changes in mean scores over three timepoints for both direct and indirect clinicians. RESULTS: There were fewer significant changes in any of the scales for direct providers (n = 87) than for indirect providers (n = 155). Direct providers became less tough-minded about substance use disorders (p = 0.002), had less negative opinions about PWID (p = 0.006) and improved their beliefs regarding OAT maintenance (p<0.001) and medical information (p = 0.004). Indirect providers reported improvements in most stigma constructs, including a significant decrease in prejudice (p<0.001), discrimination (p = 0.001), shame (p = 0.007) and fear (p = 0.001) towards PWID. CONCLUSIONS: Integrating OAT services within primary settings was associated with significantly reduced stigma constructs and improved attitudes towards PWID, possibly through increased intergroup contact between PWID and general clinical staff. Unlike most stigma reduction interventions, re-engineering clinical processes so that PWID receive their care in PCCs emerges as a multilevel stigma reduction intervention through the integration of specialized services in PCCs. Integration influences different types of stigma, and has positive effects not only on health outcomes, but also improves clinician attitudes and efficiently reduces clinician stigma.

Overreporting of adherence to hepatitis C direct-acting antiviral therapy and sustained virologic response among people who inject drugs in the HERO study.

BACKGROUND: Self-reported adherence to direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) among persons who inject drugs (PWID) is often an overreport of objectively measured adherence. The association of such overreporting with sustained virologic response (SVR) is understudied. This study among PWID aimed to determine a threshold of overreporting adherence that optimally predicts lower SVR rates, and to explore correlates of the optimal overreporting threshold. METHODS: This study analyzed per-protocol data of participants with adherence data (N = 493) from the HERO (Hepatitis C Real Options) study. Self-reported and objective adherence to a 12-week DAA regimen were measured using visual analogue scales and electronic blister packs, respectively. The difference (Δ) between self-reported and objectively measured adherence was calculated. We used the Youden index based on receiver operating characteristic (ROC) curve analysis to identify an optimal threshold of overreporting for predicting lower SVR rates. Factors associated with the optimal threshold of overreporting were identified by comparing baseline characteristics between participants at/above versus those below the threshold. RESULTS: The self-reported, objective, and Δ adherence averages were 95.1% (SD = 8.9), 75.9% (SD = 16.3), and 19.2% (SD = 15.2), respectively. The ≥ 25% overreporting threshold was determined to be optimal. The SVR rate was lower for ≥ 25% vs. < 25% overreporting (86.7% vs. 95.8%, p <.001). The factors associated with ≥ 25% Δ adherence were unemployment; higher number of days and times/day of injecting drugs; higher proportion of positive urine drug screening for amphetamine, methamphetamine, and oxycodone, and negative urine screening for THC (tetrahydrocannabinol)/cannabis. CONCLUSIONS: Self-reported DAA adherence was significantly greater than objectively measured adherence among PWID by 19.2%. Having ≥ 25% overreported adherence was associated with optimal prediction of lower SVR rates. PWID with risk factors for high overreporting may need to be more intensively managed to promote actual adherence.

Real-world hepatitis C prevalence and treatment uptake at opioid agonist therapy clinics in Ontario, Canada.

Widespread screening for hepatitis C virus (HCV) is necessary for Canada to meet its HCV elimination goals by 2030. People who currently or previously injected drugs are at high risk for HCV. Opioid agonist therapy (OAT, such as methadone and buprenorphine) has been shown to help stabilize the lives of people who are opioid-dependent. The distribution of OAT in North America typically requires daily, weekly, or monthly clinic visits and presents an opportunity for engagement, screening and treatment for those at high-risk of HCV. In this study, HCV screening was conducted by staff at OAT clinics in Ontario from 2016 to 2020 and those with chronic infections were treated on-site with direct-acting antivirals. Point-of-care or dried blood spot (DBS) testing was used for antibodies, DBS or serum for HCV RNA and serum for HCV RNA at SVR12 (sustained virological response). Clinics screened 1954 people (mean age 40 years ±12, 63% male). Forty-five percent were antibody positive, of whom 64% were HCV RNA+. Eighty percent of those RNA+ set an appointment in which 99% attended. Ninety-six percent started treatment with 87% completing treatment. Sixty-eight percent of people who completed treatment submitted a sample for SVR12 testing of which 97% achieved a virological cure. Results suggest that HCV screening and treatment at OAT clinics is feasible, effective and warrants expansion. Data suggest strong treatment adherence due to high rates of SVR12 comparable with other OAT-based HCV treatment programs. The lack of SVR12 sampling could be addressed by either on-site phlebotomy or incentivizing SVR12 sampling.

Improving access to HIV care among people who inject drugs through tele-harm reduction: a qualitative analysis of perceived discrimination and stigma.

BACKGROUND: Tele-harm reduction (THR) is a telehealth-enhanced, peer-led, harm reduction intervention delivered within a trusted syringe services program (SSP) venue. The primary goal of THR is to facilitate linkage to care and rapid, enduring virologic suppression among people who inject drugs (PWID) with HIV. An SSP in Miami, Florida, developed THR to circumvent pervasive stigma within the traditional healthcare system. METHODS: During intervention development, we conducted in-depth interviews with PWID with HIV (n = 25) to identify barriers and facilitators to care via THR. We employed a general inductive approach to transcripts guided by iterative readings of the raw data to derive the concepts, themes, and interpretations of the THR intervention. RESULTS: Of the 25 PWID interviewed, 15 were in HIV care and adherent to medication; 4 were in HIV care but non-adherent; and 6 were not in care. Themes that emerged from the qualitative analysis included the trust and confidence PWID have with SSP clinicians as opposed to professionals within the traditional healthcare system. Several barriers to treatment were reported among PWID, including perceived and actual discrimination by friends and family, negative internalized behaviors, denial of HIV status, and fear of engaging in care. Facilitators to HIV care included empathy and respect by SSP staff, flexibility of telehealth location, and an overall destigmatizing approach. CONCLUSION: PWID identified barriers and facilitators to receipt of HIV care through the THR intervention. Interviews helped inform THR intervention development, centered on PWID in the destigmatizing environment of an SSP.

Perspectives of patients who inject drugs on a needle and syringe program at a large acute care hospital.

BACKGROUND: People who inject drugs in North America often continue to inject while hospitalized, and are at increased risk of premature hospital discharge, unplanned readmission, and death. In-hospital access to sterile injection supplies may reduce some harms associated with ongoing injection drug use. However, access to needle and syringe programs in acute care settings is limited. We explored the implementation of a needle and syringe program integrated into a large urban tertiary hospital in Western Canada. The needle and syringe program was administered by an addiction medicine consult team that offers patients access to specialized clinical care and connection to community services. METHODS: We utilized a focused ethnographic design and semi-structured interviews to elicit experiences and potential improvements from 25 hospitalized people who inject drugs who were offered supplies from the needle and syringe program. RESULTS: Participants were motivated to accept supplies to prevent injection-related harms and access to supplies was facilitated by trust in consult team staff. However, fears of negative repercussions from non-consult team staff, including premature discharge or undesired changes to medication regimes, caused some participants to hesitate or refuse to accept supplies. Participants described modifications to hospital policies regarding inpatient drug use or access to an inpatient supervised consumption service as potential ways to mitigate patients' fears. CONCLUSIONS: Acute care needle and syringe programs may aid hospital providers in reducing harms and improving hospital outcomes for people who inject drugs. However, modifications to hospital policies and settings may be necessary.

Delivering integrated strategies from a mobile unit to address the intertwining epidemics of HIV and addiction in people who inject drugs: the HPTN 094 randomized controlled trial protocol (the INTEGRA Study).

BACKGROUND: Persons with opioid use disorders who inject drugs (PWID) in the United States (US) face multiple and intertwining health risks. These include interference with consistent access, linkage, and retention to health care including medication for opioid use disorder (MOUD), HIV prevention using pre-exposure prophylaxis (PrEP), and testing and treatment for sexually transmitted infections (STIs). Most services, when available, including those that address substance misuse, HIV prevention, and STIs, are often provided in multiple locations that may be difficult to access, which further challenges sustained health for PWID. HPTN 094 (INTEGRA) is a study designed to test the efficacy of an integrated, "whole-person" strategy that provides integrated HIV prevention including antiretroviral therapy (ART), PrEP, MOUD, and STI testing and treatment from a mobile health delivery unit ("mobile unit") with peer navigation compared to peer navigation alone to access these services at brick and mortar locations. METHODS: HPTN 094 (INTEGRA) is a two-arm, randomized controlled trial in 5 US cities where approximately 400 PWID without HIV are assigned either to an experimental condition that delivers 26 weeks of "one-stop" integrated health services combined with peer navigation and delivered in a mobile unit or to an active control condition using peer navigation only for 26 weeks to the same set of services delivered in community settings. The primary outcomes include being alive and retained in MOUD and PrEP at 26 weeks post-randomization. Secondary outcomes measure the durability of intervention effects at 52 weeks following randomization. DISCUSSION: This trial responds to a need for evidence on using a "whole-person" strategy for delivering integrated HIV prevention and substance use treatment, while testing the use of a mobile unit that meets out-of-treatment PWID wherever they might be and links them to care systems and/or harm reduction services. Findings will be important in guiding policy for engaging PWID in HIV prevention or care, substance use treatment, and STI testing and treatment by addressing the intertwined epidemics of addiction and HIV among those who have many physical and geographic barriers to access care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04804072 . Registered on 18 March 2021.

Injecting drug use and hepatitis C virus infection independently increase biomarkers of inflammatory disease risk which are incompletely restored by curative direct-acting antiviral therapy.

Background: Hepatitis C virus (HCV) infections are more prevalent in people who inject drugs (PWID) who often experience additional health risks. HCV induces inflammation and immune alterations that contribute to hepatic and non-hepatic morbidities. It remains unclear whether curative direct acting antiviral (DAA) therapy completely reverses immune alterations in PWID. Methods: Plasma biomarkers of immune activation associated with chronic disease risk were measured in HCV-seronegative (n=24) and HCV RNA+ (n=32) PWID at baseline and longitudinally after DAA therapy. Adjusted generalised estimating equations were used to assess longitudinal changes in biomarker levels. Comparisons between community controls (n=29) and HCV-seronegative PWID were made using adjusted multiple regression modelling. Results: HCV-seronegative PWID exhibited significantly increased levels of inflammatory biomarkers including soluble (s) TNF-RII, IL-6, sCD14 and sCD163 and the diabetes index HbA1c as compared to community controls. CXCL10, sTNF-RII, vascular cell adhesion molecule-1 and lipopolysaccharide binding protein (LBP) were additionally elevated in PWID with viremic HCV infection as compared to HCV- PWID. Whilst curative DAA therapy reversed some biomarkers, others including LBP and sTNF-RII remained elevated 48 weeks after HCV cure. Conclusion: Elevated levels of inflammatory and chronic disease biomarkers in PWID suggest an increased risk of chronic morbidities such as diabetes and cardiovascular disease. HCV infection in PWID poses an additional disease burden, amplified by the incomplete reversal of immune dysfunction following DAA therapy. These findings highlight the need for heightened clinical surveillance of PWID for chronic inflammatory diseases, particularly those with a history of HCV infection.

Impact of harm minimization interventions on reducing blood-borne infection transmission and some injecting behaviors among people who inject drugs: an overview and evidence gap mapping.

BACKGROUND: This study aimed to synthetize the evidence on the effectiveness of harm minimization interventions on reducing blood-borne infection transmission and injecting behaviors among people who inject drugs (PWID) through a comprehensive overview of systematic reviews and evidence gap mapping. METHODS: A systematic review was conducted with searches in PubMed and Scopus to identify systematic reviews assessing the impact of interventions aimed at reducing the harms associated with injectable drug use. The overall characteristics of the studies were extracted and their methodological quality was assessed using AMSTAR-2. An evidence gap map was constructed, highlighting the most frequently reported outcomes by intervention (CRD42023387713). RESULTS: Thirty-three systematic reviews were included. Of these, 14 (42.2%) assessed the impact of needle/syringe exchange programs (NSEP) and 11 (33.3%) examined opioid agonist therapy (OAT). These interventions are likely to be associated with reductions of HIV/HCV incidence (10-40% risk reduction for NSEP; 50-60% for OAT) and sharing injecting paraphernalia (50% for NSEP, 25-85% for OAT), particularly when combined (moderate evidence). Behavioral/educational interventions were assessed in 12 reviews (36.4%) with most authors in favor/partially in favor of the use of these approaches (moderate evidence). Take-home naloxone programs and supervised-injection facilities were each assessed in two studies (6.1%), which reported inconclusive results (limited/inconsistent evidence). Most authors reported high levels of heterogeneity and risk of bias. Other interventions and outcomes were inadequately reported. Most systematic reviews presented low or critically low quality. CONCLUSION: The evidence is sufficient to support the effectiveness of OAT, NSEP and their combination in reducing blood-borne infection transmission and certain injecting behaviors among PWID. However, evidence of other harm minimizations interventions in different settings and for some outcomes remain insufficient.

Loneliness and fearfulness are associated with non-fatal drug overdose among people who inject drugs.

BACKGROUND: People who inject drugs (PWID) experience high rates of drug overdose death with the risk of mortality increasing after each non-fatal event. Racial differences exist in drug overdose rates, with higher rates among Black people who use drugs. Psychological factors may predict drug overdose. METHODS: Cross-sectional data from a survey administered to PWID in Baltimore, MD enrolled in a social network-based intervention were analyzed. Linear regression methods with generalized estimating equations were used to analyze data from indexes and network members to assess for psychological factors significantly associated with self-reported number of lifetime drug overdoses. Factors associated with number of overdoses were assessed separately by race. RESULTS: Among 111 PWID enrolled between January 2018 and January 2019, 25.2% were female, 65.7% were Black, 98.2% reported use of substances in addition to opioids, and the mean age was 49.0 ± 8.3 years. Seventy-five individuals (67.6%) had a history of any overdose with a mean of 5.0 ± 9.7 lifetime overdoses reported. Reports of feeling fearful (ß = 9.74, P = 0.001) or feeling lonely all of the time (ß = 5.62, P = 0.033) were independently associated with number of drug overdoses. In analyses disaggregated by race, only the most severe degree of fearfulness or loneliness was associated with overdose among Black participants, whereas among White participants, any degree of fearfulness or loneliness was associated with overdose. CONCLUSIONS: In this study of PWID loneliness and fearfulness were significantly related to the number of reported overdose events. These factors could be targeted in future interventions.

Infective Endocarditis in Patients Addicted to Injected Opioid Drugs.

BACKGROUND: Persons who inject drugs and require surgery for infective endocarditis have 2 potentially lethal diseases. Current postoperative rehabilitation efforts seem ineffective in preventing loss to follow-up, injection drug use relapse (relapse), and death. OBJECTIVES: The purpose of this study was to characterize drug use, psychosocial issues, surgical outcome, and postoperative addiction management, as well as loss to follow-up, relapse, and mortality and their risk factors. METHODS: From January 2010 to June 2020, 227 persons who inject drugs, age 36 ± 9.9 years, underwent surgery for infective endocarditis at a quaternary hospital having special interest in developing addiction management programs. Postsurgery loss to follow-up, relapse, and death were assessed as competing risks and risk factors identified parametrically and by machine learning. CIs are 68% (±1 SE). RESULTS: Heroin was the most self-reported drug injected (n = 183 [81%]). Psychosocial issues included homelessness (n = 56 [25%]), justice system involvement (n = 150 [66%]), depression (n = 118 [52%]), anxiety (n = 104 [46%]), and post-traumatic stress disorder (n = 33 [15%]). Four (1.8%) died in-hospital. Medication for opioid use disorder prescribed at discharge increased from 0% in 2010 to 100% in 2020. At 1 and 5 years, conditional probabilities of loss to follow-up were 16% (68% CI: 13%-22%) and 59% (68% CI: 44%-65%), relapse 32% (68% CI: 28%-34%) and 79% (68% CI: 74%-83%), and mortality 21% (68% CI: 18%-23%) and 68% (68% CI: 62%-72%). Younger age, heroin use, and lower education level were predictors of relapse. CONCLUSIONS: Infective endocarditis surgery can be performed with low mortality in persons who inject drugs, but addiction is far more lethal. Risk of loss to follow-up and relapse require more effective addiction strategies without which this major loss to society will continue.

WaSH insecurity and anxiety among people who inject drugs in the Tijuana-San Diego border region.

BACKGROUND: Water, sanitation, and hygiene (WaSH) insecurity increases the risk of water-related diseases. However, limited research has been conducted on psychosocial distress as it relates to WaSH insecurity, especially among people who inject drugs (PWID). We examined the relationship between WaSH insecurity and related anxiety among PWID living in different housing conditions along the US-Mexico border region. METHODS: From 2020-2021, a cross-sectional study was conducted among 585 people who injected drugs within the last month in Tijuana (N = 202), San Diego (N = 182), and in both Tijuana and San Diego (N = 201). Participants underwent interviewer-administered surveys related to WaSH access, substance use, and generalized anxiety disorder (GAD-7). Quasi-Poisson regressions were used to assess associations between WaSH insecurity and anxiety in the prior 6-months. RESULTS: Participants were 75% male, 42% were unhoused and 91% experienced WaSH insecurity in the prior 6-months. After adjusting for housing status, gender, and age, lack of access to basic drinking water (Adj RR: 1.28; 95% CI: 1.02-1.58), sanitation (Adj RR:1.28; 95% CI: 1.07-1.55), and a daily bath/shower (Adj RR: 1.38; 95% CI: 1.15-1.66) were associated with mild-severe anxiety. The number of WaSH insecurities was independently associated with a 20% increased risk of experiencing anxiety per every additional insecurity experienced (Adj RR: 1.20; CI: 1.12-1.27). We also found a significant interaction between gender and housing status (p = 0.003), indicating that among people experiencing sheltered/unsheltered homelessness, women had a higher risk of mild-severe anxiety compared to men (Adj RR: 1.55; 95% CI: 1.27-1.89). At the same time, among women, those who are unhoused have 37% increased risk of anxiety than those who live in stable housing conditions (Adj RR: 1.37; 95% CI: 1.01-1.89). CONCLUSION: The lack of specific WaSH services, particularly lack of drinking water, toilets, and daily showers were associated with higher levels of anxiety among PWID in the Tijuana-San Diego border region. Women experiencing homelessness were especially vulnerable. WaSH interventions that provide safe, 24-h access may help to reduce anxiety and health risks associated with WaSH insecurity.