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BACKGROUND: Drug injection is a major health-related problem worldwide. Injection cessation and relapse to injection could significantly alter the risk of HIV and hepatitis C virus (HCV) among people who inject drugs (PWID). This study aimed to estimate the rate of injection cessation and relapse to injection among PWID in Iran. METHODS: This cohort study was conducted from 2018 to 2021 in the cities of Kerman and Tehran. Using a respondent-driven sampling (RDS) approach, 118 PWID with a history of injection in the last six months and negative HIV and HCV tests were recruited. Follow-up visits occurred every three months over a period of one year. Participants were interviewed and tested for HIV and HCV using rapid tests. Injection cessation was defined as the no injection of any type of drugs in the last three months. Relapse to injection was defined as re-initiating drug injection among those who had ceased injection. Two separate Cox regression models were applied, and an adjusted hazard ratio (aHR) with a 95% confidence interval (CI) were measured to assess the factors associated with each outcome. RESULTS: The rate of injection cessation was 26.1 (95% CI: 21.3, 32.0) per 100 person-years, and the rate of relapse to injection was 32.7 (95% CI: 24.7, 43.2) per 100 person-years. At the baseline interview, 39.8% (n = 47) of participants reported injection cessation in the past three months before the interview. In the multivariable Cox regression analysis, the rate of relapse to injection was greater among women (aHR = 1.58; 95% CI: 1.01, 2.52), and those with higher monthly income (aHR = 1.63; 95% CI: 1.03, 2.59). However, there was no significant variable that predicted injection cessation. CONCLUSION: Injection cessation was common among PWID in Iran, however, one-third relapsed to injection shortly after cessation. Harm reduction programs should include comprehensive strategies to reduce the probability of relapse among PWID who achieve injection cessation.

BACKGROUND: People who inject drugs (PWID) continue to experience the highest burden of hepatitis C virus (HCV). We aimed to characterize HCV antibody prevalence, determinants of infection, and the cascade of engagement in HCV care among PWID in Iran. METHODS: Participants were recruited in 11 cities of Iran using respondent-driven sampling. PWID underwent a structured interview capturing measures on socio-demographics, behaviors, and the HCV cascade of care. HCV and HIV were tested using antibody rapid tests. Multivariable logistic regression models identified characteristics associated with HCV seropositivity. RESULTS: HCV antibody prevalence was 26.0% among 2684 PWID enrolled. Of 699 participants who were HCV antibody positive, 88 (12.6%) were aware of past infections. HCV antibody prevalence was associated with older age (adjusted odds ratio [aOR] 2.09; 95% CI 1.18, 3.71), lower education (aOR 1.31; 95% CI 1.02, 1.69), >10 years of injecting (aOR 6.03; 95% CI 4.10, 8.85), methamphetamine injection (aOR 1.46; 95% CI 1.07, 1.99), daily injection drug use (aOR 1.26; 95% CI 1.01, 1.58), needle/syringe sharing (aOR 2.04; 95% CI 1.24, 3.34), recent incarceration (aOR 1.74; 95% CI 1.30, 2.32), and HIV seropositivity (aOR 7.93; 95% CI 4.12, 15.24). Additionally, 12.0% had ever tested for HCV, 4.0% had previously tested reactive for HCV antibody, and 3.7% had received an HCV diagnosis. Of diagnosed cases, 44.4% were linked to care, 15.2% initiated treatment, and 3.0% achieved sustained virologic response. CONCLUSION: Our data show a high prevalence of HCV antibody and low engagement in HCV care, underscoring an unmet need for HCV prevention, screening, and treatment among PWID in Iran. HCV prevention and treatment programs tailored for PWID are needed to enhance harm reduction efforts and access to HCV care in Iran.

BackgroundPeople who inject drugs (PWID) are at high risk for hepatitis C virus (HCV) infection and its complications in many countries, including Iran. This pilot study aimed to evaluate the effect of a community-based HCV model of care on HCV testing and treatment initiation among PWID in Kerman, Iran.MethodsThis study is part of the Rostam study and is a non-randomized trial evaluating the effect of on-site HCV- antibody rapid testing, venipuncture for HCV RNA testing, and treatment eligibility assessment on HCV testing and treatment initiation among PWID. Recruitment, interviews, and HCV screening, diagnosis, and treatment were all conducted at a community-based drop-in center (DIC) serving PWID clients.ResultsA total of 171 PWID (median age of 39 years and 89.5% male) were recruited between July 2018 and May 2019. Of 62 individuals who were HCV antibody positive, 47 (75.8%) were HCV RNA positive. Of RNA-positive individuals, 36 (76.6%) returned for treatment eligibility assessment. Of all the 36 participants eligible for treatment, 34 (94.4%) initiated HCV antiviral therapy. A sustained virologic response at 12 weeks post-treatment was 76.5% (26/34) in the intention-to-treat (ITT group) analysis and 100% (23/23) in the per-protocol (PP group) analysis.ConclusionOur integrated on-site community-based HCV care model within a DIC setting suggested that HCV care including HCV testing and treatment uptake can be successfully delivered outside of hospitals or specialized clinics; a model which is more likely to reach PWID and can provide significant progress towards HCV elimination among this population.

BackgroundUnderstanding the reasons for loss to follow-up (LTFU) in cohort studies, especially among marginalized groups such as people who inject drugs (PWID), is needed to strengthen the rigor of efficacy trials for prevention and treatment interventions. We assessed the proportion and reasons for loss to follow-up in a recent cohort of PWID enrolled in the southeast of Iran.MethodsUsing respondent-driven sampling, we recruited 98 PWID age 18 years or older who reported injecting drugs in the past 6 months, and were negative for HIV and HCV at initial screening. Participants were followed at 6 week intervals, alternating a short six-week visit and long 12-week or quarterly visit to measure incidence of HIV and HCV. Methods to enhance retention included incentives for completing each visit, tracking people who missed the scheduled visits through their peer referral networks, engaged outreach teams to explore hotspots and residences, and photos. LTFU was defined as participants who missed their quarterly visits for two or more weeks.ResultsMean (SD) age of participants was 39.7 years (SD 9.6). Of 98 enrolled, 50 participants (51.0%) were LTFU by missed their scheduled quarterly visits for 2 weeks or more. For those whose reasons for LTFU could be defined (46.0%, 23 of 50), main reasons were: forgetting the date of visit (43.5%, 10 of 23), being incarcerated (39.1%, 9 of 23), and moving out of the city (17.4%, 4 of 23).ConclusionThis study highlighted the difficulty in retaining PWID in longitudinal studies. Despite having several retention strategies in place, over half of PWID were LTFU. The LTFU might be reduced by setting up more effective reminder systems, working closely with security systems, and online means to reach those who move outside the study area.

Objectives: There is limited evidence on how opioid agonist treatment (OAT) may affect psychoactive non-opioid substance use in prescription-type opioid use disorder (POUD) and whether this effect might explain OAT outcomes. We aimed to assess the effect of methadone on non-opioid substance use compared to buprenorphine/naloxone (BUP/NX), to explore whether non-opioid substance use is associated with opioid use and retention in treatment, and to test non-opioid use as a moderator of associations between methadone with retention in OAT and opioid use compared to BUP/NX. Methods: This is a secondary analysis of data from the OPTIMA trial, an open-label, pragmatic, parallel, two-arm, pan-Canadian, multicentre, randomized-controlled trial to compare standard methadone model of care and flexible take-home dosing BUP/NX for POUD treatment. We studied the effect of methadone and BUP/NX on non-opioid substance use evaluated by urine drug screen (UDS) and by classes of non-opioid substances (i.e., tetrahydrocannabinol [THC], benzodiazepines, stimulants) (weeks 2–24) using adjusted generalized estimation equation (GEE). We studied the association between non-opioid substance-positive UDS and opioid-positive UDS and retention in treatment, using adjusted GEE and logistic regressions. Results: Overall, methadone was not associated with non-opioid substance-positive UDS compared to BUP/NX (OR: 0.78; 95%CI, 0.41 to 1.48). When non-opioid substances were studied separately, methadone was associated with lower odds of benzodiazepine-positive UDS (OR: 0.63; 95% CI: 0.40 to 0.98) and THC-positive UDS (OR: 0.47; 95% CI: 0.28 to 0.77), but not with different odds of stimulant-positive UDS (OR: 1.29; 95% CI: 0.78 to 2.16) compared to BUP/NX. Substance-positive UDS, overall and separate classes, were not associated with opioid-positive UDS or retention in treatment. Conclusion: Methadone did not show a significant effect on overall non-opioid substance use in POUD compared to BUP/NX treatment but was associated with lower odds of benzodiazepine and THC use in particular. Non-opioid substance use did not predict OAT outcomes. Further research is needed to ascertain whether specific patterns of polysubstance use (quantity and frequency) may affect treatment outcomes. [ABSTRACT FROM AUTHOR]

Background and Aims: There is currently no standard of care for pharmacological treatment of amphetamine‐type stimulant (ATS) use disorder (ATSUD). This systematic review with meta‐analysis (PROSPERO CRD42022354492) aimed to pool results from randomized placebo‐controlled trials (RCTs) to evaluate efficacy and safety of prescription psychostimulants (PPs) for ATSUD. Methods: Major indexing sources and trial registries were searched to include records published before 29 August 2022. Eligible studies were RCTs evaluating efficacy and safety of PPs for ATSUD. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. Risk ratio (RR) and risk difference were calculated for random‐effect meta‐analysis of dichotomous variables. Mean difference and standardized mean difference (SMD) were calculated for random‐effect meta‐analysis of continuous variables. Results: Ten RCTs (n = 561 participants) were included in the meta‐analysis. Trials studied methylphenidate (n = 7), with daily doses of 54–180 mg, and dextroamphetamine (n = 3), with daily doses of 60–110 mg, for 2–24 weeks. PPs significantly decreased end‐point craving [SMD −0.29; 95% confidence interval (CI) = −0.55, −0.03], while such a decrease did not reach statistical significance for ATS use, as evaluated by urine analysis (UA) (RR = 0.93; 95% CI = 0.85–1.01). No effect was observed for self‐reported ATS use, retention in treatment, dropout following adverse events, early‐stage craving, withdrawal and depressive symptoms. In a sensitivity analysis, treatment was associated with a significant reduction in UA positive for ATS (RR = 0.89; 95% CI = 0.79–0.99) after removing studies with a high risk of bias. In subgroup analyses, methylphenidate and high doses of PPs were negatively associated with ATS use by UA, while higher doses of PPs and treatment duration (≥ 20 weeks) were positively associated with longer retention. Conclusions: Among individuals with amphetamine‐type stimulant use disorder, treatment with prescription psychostimulants may decrease ATS use and craving. While effect size is limited, it may increase with a higher dosage of medications. [ABSTRACT FROM AUTHOR]

Amphetamine-type stimulants (ATSs) are related to significant harm worldwide, with limited effective pharmacological treatments for ATS use disorder (ATSUD). Modafinil has been explored as a potential treatment for ATSUD. This systematic review and meta-analysis (PROSPERO ID: CRD42023388487) aimed to evaluate the efficacy and safety of modafinil for the treatment of ATSUD.A comprehensive search of major indexing sources and trial registries, from inception to search date, was conducted on February 15, 2023, and updated on October 31, 2023. Eligible studies were randomized placebo-controlled trials (RCTs) of modafinil in individuals meeting the criteria for the Diagnostic and Statistical Manual of Mental Disorders, fourth and fifth editions, diagnoses of ATSUD. Eligible studies were assessed for risk of bias, using the Cochrane Risk of Bias tool. The primary outcome included the effect of modafinil on ATS use. Secondary outcomes included retention in treatment, ATS craving, treatment discontinuation due to adverse events (AEs), and serious AEs. Subgroup analysis by modafinil dose was conducted where appropriate. Risk ratio (RR) or Peto's odds ratio (OR) was calculated for the meta-analysis of dichotomous variables and standardized mean difference (SMD) was calculated for the random-effect meta-analysis of continuous variables.Five RCTs (N = 451 participants) were included. Modafinil did not significantly impact ATS use (RR = 0.99; 95% CI, 0.97 to 1.02; p = 0.655), retention in treatment (RR = 1.02; 95% CI, 0.91 to 1.14; p = 0.799), ATS craving (SMD = −0.36; 95% CI, −1.19 to 0.47; p = 0.398), or treatment discontinuation due to AEs (Peto's OR = 0.48; 95% CI, 0.20 to 1.14; p = 0.100). These results were consistent across subgroup analyses. More episodes of serious AEs were reported in the modafinil group than in the placebo group, at higher doses (Peto's OR = 4.80; 95% CI, 1.18 to 19.56, p = 0.029).There is currently no evidence suggesting that modafinil has a statistically significant effect on efficacy outcomes in populations with ATSUD. Continued research into effective treatments and harm reduction strategies for ATSUD is essential. [ABSTRACT FROM AUTHOR]