Prescription psychostimulants for the treatment of amphetamine-type stimulant use disorder: A systematic review and meta-analysis of randomized placebo-controlled trials.

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.

Injection cessation and relapse to injection and the associated factors among people who inject drugs in Iran: The Rostam study.

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.

Bupropion for treatment of amphetamine-type stimulant use disorder: A systematic review and meta-analysis of placebo-controlled randomized clinical trials.

BACKGROUND: This meta-analysis (PROSPERO-ID: CRD42022362962), pooled effect estimates of outcomes, from placebo-controlled randomized clinical trials (RCTs) examining bupropion efficacy and safety for amphetamine-type stimulant use disorder (ATSUD) treatment. METHOD: Electronic databases were searched for records published to October 31st, 2022, including MEDLINE, CINAHL, PsycINFO, EBM Reviews, EMBASE, PubMed, Web of Science, trial registries. Inclusion criteria were RCTs comparing bupropion to placebo in ATSUD. Cochrane RoB2 tool and GRADE evidence certainty assessment were employed. Outcomes included amphetamine-type stimulant (ATS) use by urinalysis, retention in treatment, treatment adherence, ATS craving, addiction severity, depressive symptom severity, drop-out following adverse events (AEs), and serious AEs. Random-effect meta-analysis was conducted presenting standardized mean difference (SMD), risk ratio (RR), and risk difference (RD). RESULTS: Eight RCTs (total N=1239 participants) were included. Bupropion compared to placebo was associated with reduced ATS use (RR: 0.90; 95% CI: 0.84, 0.96), end-of-treatment ATS craving (SMD: -0.38; 95%CI: -0.63, -0.13), and adherence (RR: 0.91; 95%CI: 0.84, 0.99). Subgroup analysis showed greater reduction in ATS use with longer trial duration (12 weeks) (RR: 0.85; 95%CI: 0.78, 0.93) and greater reduction in end-of-treatment ATS craving in studies with mixed ATS use frequency (SMD: -0.46; 95%CI: -0.70, -0.22) and male-only samples (SMD: -1.26; 95%CI: -1.87, -0.65). CONCLUSION: Bupropion showed a significant modest reduction in ATS use and ATS craving (both rated as very low-quality evidence), larger in males (craving), and with longer treatment (ATS use). These results may inform future studies. More research is warranted on who might benefit from bupropion as ATSUD treatment.

Associations Between Buprenorphine\Naloxone and Methadone Treatment and non-Opioid Substance Use in Prescription-Type Opioid Use Disorder: Secondary Analyses From the OPTIMA Study: Associations entre le traitement avec la buprénorphine/naloxone et avec la méthadone et l'utilisation de substances non opioïdes dans le trouble lié à l'usage d'opioïdes de type sur ordonnance : analyses secondaires de l'étude OPTIMA.

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.

Trends in the Prevalence of Hepatitis B Virus, Hepatitis C Virus, and HIV Infections in Iranian Patients with Hereditary Bleeding Disorders.

BACKGROUND: Patients with hereditary bleeding disorders (HBDs) have always been vulnerable to transfusion-transmitted infections (TTIs) such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections due to being regular recipients of blood and blood products. This study aimed to detect the trends in the prevalence of HBV, HCV, and HIV infections by birthyear in Iranian patients with HBDs to show the efficacy of national interventions implemented to administrate control and to prevent these infections, i.e., blood safety, newborn HBV vaccination, and safe replacement treatments. METHODS: In this retrospective study, the trends in the prevalence of hepatitis B core antibody (HBcAb), HCV antibody (HCV-Ab), and HIV antibody (HIV-Ab) in Iranian patients with HBDs born before 2012 were assessed using patients' clinical archives. The determinants of HBV, HCV, and HIV infections were investigated in bivariable and multivariable logistic regression analyses. RESULTS: Out of 1475 patients with HBDs, most were male (87.7%) and diagnosed with hemophilia A (52.1%) and severe bleeding disorder (63.7%). The prevalence of HBcAb, HCV-Ab, and confirmed HIV-Ab was 22.9%, 59.8%, and 1.2%, respectively. The trends in HBcAb, HCV-Ab, and HIV-Ab were all decreasing by birthyear and reached a stable level of 0% for patients with birthyears in 1999, 2000, and 1984, respectively. In multivariable analysis, birthyear was significantly associated with HBcAb prevalence. In the multivariable analysis, type of HBD; birthyear; bleeding severity; histories of receiving packed cells, fresh frozen plasma, and cryoprecipitate before 1996; and history of receiving factor concentrate before 1997 were highly associated with the prevalence of HCV-Ab. Moreover, in the bivariable analysis, birthyear and type of HBD were associated with HIV-Ab prevalence. CONCLUSION: This study demonstrated the decreasing trends in HBV, HCV, and HIV seroprevalence in Iranian patients with HBDs following preventive interventions such as HBV vaccination, blood safety measures, and the provision of safe replacement treatments.

Hepatitis C virus prevalence, determinants, and cascade of care among people who inject drugs in Iran.

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.

Economic evaluation of pan-genotypic generic direct-acting antiviral regimens for treatment of chronic hepatitis C in Iran: a cost-effectiveness study.

INTRODUCTION: Low-cost generic direct-acting antiviral (DAA) regimens for treatment of hepatitis C virus (HCV) are available in several low-income/middle-income countries, important for treatment scale-up. This study evaluated the cost-effectiveness of genotype-dependent and pan-genotypic DAA regimens in Iran as an example of a resource-limited setting. METHODS: A Markov model was developed to simulate HCV natural history. A decision tree was developed for HCV treatment, assuming four scenarios, including scenario 1: genotyping, sofosbuvir/ledipasvir (SOF/LDV) for genotype 1, and sofosbuvir/daclatasvir (SOF/DCV) for genotype 3; scenario 2: genotyping, SOF/LDV for genotype 1, and sofosbuvir/velpatasvir (SOF/VEL) for genotype 3; scenario 3: no genotyping and SOF/DCV for all; and scenario 4: no genotyping and SOF/VEL for all. A 1-year cycle length was used to calculate the cumulative cost and effectiveness over a lifetime time horizon. We calculated quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) using a health system perspective. Costs were converted to US dollars using purchasing power parity exchange rate ($PPP). All costs and outcomes were discounted at an annual rate of 3%. RESULTS: Among people with no cirrhosis, scenario 3 had the minimum cost, compared with which scenario 4 was cost-effective with an ICER of 4583 $PPP per QALY (willingness-to-pay threshold: 9,311 $PPP per QALY). Among both people with compensated or decompensated cirrhosis, scenario 4 was cost saving. In sensitivity analysis, scenario 4 would be also cost-saving among people with no cirrhosis provided a 39% reduction in the cost of 12 weeks SOF/VEL. CONCLUSION: Initiating all patients on pan-genotypic generic DAA regimens with no pretreatment genotyping was cost-effective compared with scenarios requiring pretreatment HCV genotype tests. Among generic pan-genotypic DAA regimens, SOF/VEL was cost-effective, for people with no cirrhosis and cost-saving for those with cirrhosis.

Association of single nucleotide polymorphisms in immune-related genes with spontaneous HBsAg seroconversion: A systematic review and meta-analysis.

BACKGROUND: Studies have reported that the immune system modulation genes are involved in the seroconversion during hepatitis B virus (HBV) infection. Here, a systematic review with meta-analysis is implemented on the association of polymorphisms in immune-related genes with the spontaneous hepatitis B surface antigen (HBsAg) seroconversion. METHODS: A systematic literature search was conducted in the main electronic databases of Scopus, PubMed, and Web of Science before May 2022. Pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were used to evaluate the strength of the association between genetic polymorphisms and the chance of spontaneous HBsAg seroconversion. RESULTS: A total of 40 studies finally included for meta-analysis of 2 HLA-DP SNPs, 2 HLA-DQ SNPs, 3 IFNL3/4 SNPs, 2 IL10 SNPs, and 5 TNF SNPs. Based on the overall pooled analysis, HLA-DP rs3077 A (OR = 1.47, 95%CI: 1.32-1.65), HLA-DP rs9277535 A (OR = 1.48, 95%CI: 1.32-1.66), HLA-DQ rs2856718 G (OR = 1.37, 95%CI: 1.18-1.59), HLA-DQ rs7453920 A (OR = 1.41, 95%CI: 1.04-1.93), IFNL3/4 rs12980275 G (OR = 1.26, 95%CI: 1.01-1.58), TNFA rs1799964 T (OR = 1.17, 95%CI: 1.02-1.35), and TNFA rs1800630 C (OR = 1.26, 95%CI: 1.03-1.55) increased significantly the chance of spontaneous HBsAg seroconversion. CONCLUSION: This meta-analysis showed that the HLA-DP gene rs3077 and rs9277535 SNPs, HLA-DQ gene rs2856718 and rs7453920 SNPs, IFNL3/4 gene rs12980275 SNP, TNFA gene rs1799964 and rs1800630 SNPs are involved in the spontaneous HBsAg seroconversion.

An on-site community-based model for hepatitis C screening, diagnosis, and treatment among people who inject drugs in Kerman, Iran: The Rostam study.

BACKGROUND: People 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. METHODS: This 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. RESULTS: A 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. CONCLUSION: Our 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.

First report on molecular docking analysis and drug resistance substitutions to approved HCV NS5A and NS5B inhibitors amongst Iranian patients.

BACKGROUND: NS5A and NS5B proteins of hepatitis C virus (HCV) are the main targets of compounds that directly inhibit HCV infections. However, the emergence of resistance-associated substitutions (RASs) may cause substantial reductions in susceptibility to inhibitors. METHODS: Viral load and genotyping were determined in eighty-seven naïve HCV-infected patients, and the amplified NS5A and NS5B regions were sequenced by Sanger sequencing. In addition, physicochemical properties, structural features, immune epitopes, and inhibitors-protein interactions of sequences were analyzed using several bioinformatics tools. RESULTS: Several amino acid residue changes were found in NS5A and NS5B proteins; however, we did not find any mutations related to resistance to the treatment in NS5B. Different phosphorylation and few glycosylation sites were assessed. Disulfide bonds were identified in both proteins that had a significant effect on the function and structure of HCV proteins. Applying reliable software to predict B-cell epitopes, 3 and 5 regions were found for NS5A and NS5B, respectively, representing a considerable potential to induce the humoral immune system. Docking analysis determined amino acids involved in the interaction of inhibitors and mentioned proteins may not decrease the drug efficiency. CONCLUSIONS: Strong interactions between inhibitors, NS5A and NS5B proteins and the lack of efficient drug resistance mutations in the analyzed sequences may confirm the remarkable ability of NS5A and NS5B inhibitors to control HCV infection amongst Iranian patients. The results of bioinformatics analysis could unveil all features of both proteins, which can be beneficial for further investigations on HCV drug resistance and designing novel vaccines.

Prevalence of Hepatitis B and Hepatitis C Infections among Incarcerated Individuals in Iran: A Cross-Sectional National Bio-behavioral Study in 2019.

Introduction: To realize the global goals of eliminating hepatitis B virus (HBV) and hepatitis C virus (HCV) by 2030, it is necessary to monitor the status of disease among target populations and undertake the required interventions. This study is the third round of surveys to determine the prevalence of hepatitis B and C infections among incarcerated individuals in different provinces of Iran. Methods: This study was conducted in five provinces of Iran (including Kurdistan, Ardabil, West Azerbaijan, Markazi, and Semnan) in 2019. The subjects of the study were selected from incarcerated people in prisons of all provinces that had not been studied in the previous two rounds of the surveys (in 2015 and 2016) in Iran. In this study, 15 prisons were selected and 2475 incarcerated individuals were enrolled into the study based on the multistage sampling method; the selected subjects were surveyed and their dried blood spot (DBS) samples were collected to test HBsAg and HCV-Ab. In cases with a reactive result for HCV-Ab, an HCV-RNA test was also performed on their serum samples. The relationships between independent variables and outcomes were evaluated via logistic regression. Results: Of all participants (2475 subjects) enrolled in the study, 54.18% were selected from northern provinces and 45.82% from the central provinces. The prevalence of HCV-Ab and HBsAg among incarcerated individuals was 5.66% (95% CI: 4.81% to 6.64%) and 2.42% (95% CI: 1.89% to 3.11%), respectively. Among HCV-seropositive individuals, 73.68% (95% CI: 64.70% to 81.01%) had current HCV infection (detectable HCV-RNA). The results showed that histories of imprisonment, drug use, unprotected sexual contact, drug injection, tattooing, and younger age in the first-time drug use in incarcerated individuals significantly increased the risk of HCV transmission. Among these behaviors, drug injection was more likely than other behaviors to result in contracting HCV in incarcerated individuals (OR: 22.91; 95% CI: 14.92-35.18; p < 0.001). Conclusion: To achieve international and national strategies targeted to eliminate HCV and HBV by 2030, it is necessary to pay special attention to prisons in Iran. It is recommended to continue HBV vaccination of eligible people in prisons. Developing screening and treatment protocols for individuals with HCV infection in prisons can help the country to achieve HCV elimination goals.

Treatment of hepatitis C virus infection with direct-acting antiviral agent-based regimens in Iranian patients with hereditary bleeding disorders.

BACKGROUND: Chronic hepatitis C (CHC) is one of the most important comorbidities in patients with hereditary bleeding disorders (HBD). The present study aimed at evaluating the effectiveness of direct-acting antiviral agent (DAA)-based interferon-free HCV antiviral regimens in patients with HBD. PATIENTS AND METHODS: The present study was performed on the patients with HBD and CHC between 2015 and 2019. Sofosbuvir-based interferon-free regimens with or without ribavirin were prescribed to treat HCV infection. The main endpoint of the study was to determine the sustained virologic response (SVR), assessed 12 weeks after the completion of treatment. RESULTS: A total of 147 patients with a mean age of 41.1 years were enrolled in the study; 4.1% of them were co-infected with HIV, 25.2% had cirrhosis, and 76.9% of them were diagnosed with hemophilia A. HCV genotype-1 includes the largest number (68.1%) of patients. 46.3% of patients were treatment-naïve and others had a treatment history with interferon-based regimens. Out of 147 patients, 15 patients were lost to follow-up during treatment or for SVR evaluation or discontinued treatment. 132 subjects completed treatment and were evaluated for SVR, 12 weeks after the completion of treatment. All of the patients achieved SVR 12 (SVR rate: 100%, 95% CI 97.2-100%). CONCLUSION: Hepatitis C DAA-based regimens are the effective treatments for CHC in patients with HBD, regardless of the treatment modifiers such as previous treatment experience, cirrhosis, HIV co-infection, and HCV genotype.

Proportion and reasons for loss to follow-up in a cohort study of people who inject drugs to measure HIV and HCV incidence in Kerman, Iran.

BACKGROUND: Understanding 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. METHODS: Using 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. RESULTS: Mean (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). CONCLUSION: This 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.

Harm reduction program and hepatitis C prevalence in people who inject drugs (PWID) in Iran: an updated systematic review and cumulative meta-analysis.

BACKGROUND: Prevalence of hepatitis C virus (HCV) infection among people who inject drugs (PWID) in Iran is high. Since 2005, the Iranian government has implemented a harm reduction program to control HCV. We aimed to describe the prevalence of HCV antibody (Ab) in Iranian PWID before and after the implementation of harm reduction with cumulative meta-analysis. METHODS: Following PRISMA guidelines, we conducted a systematic review and meta-analysis of studies published on the seroprevalence of HCV among PWID. We systematically reviewed the literature to identify eligible studies up to December 2018 in international and national databases. Pooled prevalence and 95% confidence intervals were calculated using Der Simonian and Laird method, taking into account conceptual heterogeneity. Subgroup analyses were performed by harm reduction implementation and studies' characteristics to assess the sources of heterogeneity. We used Cochran-Armitage test for the linear trend of the prevalence of HCV Ab among PWID. RESULTS: We reviewed 5966 papers and reports and extracted data from 62 eligible records. The pooled HCV Ab prevalence among PWID in Iran was 46.5% (95% confidence interval [95% CI] 41.1-52.0%). Overall, the Cochran-Armitage test for trend indicated a significant decreasing trend of HCV Ab prevalence (P = 0.04). The cumulative meta-analysis showed a slight decline in the prevalence of HCV Ab between the years 2005 and 2018. CONCLUSIONS: The HCV Ab prevalence among PWID in Iran is high, with a considerable geographical variation. The prevalence of HCV Ab among PWID in Iran slightly decreased after 2005 which could be, at least to some extent, related to the implementation of extensive harm reduction programs in the country.

Continuum of hepatitis C care cascade in prison and following release in the direct-acting antivirals era.

BACKGROUND: People with criminal justice involvement contribute remarkably to the rising hepatitis C virus (HCV) burden; however, the continuum of care is a major barrier to prison-based programs. We aimed to evaluate a comprehensive HCV care model in an Iranian provincial prison. METHODS: Between 2017-2018, in the Karaj Central Prison, newly admitted male inmates received HCV antibody testing and venipuncture for RNA testing (antibody-positive only). Participants with positive RNA underwent direct-acting antiviral (DAA) therapy (Sofosbuvir/Daclatasvir). Sustained virological response was evaluated at 12 weeks post-treatment (SVR12). RESULTS: Overall, from 3485 participants, 182 (5.2%) and 117 (3.4%) tested positive for HCV antibody and RNA, respectively. Among 116 patients who were eligible for treatment, 24% (n = 28) were released before treatment and 72% (n = 83) initiated DAA therapy, of whom 81% (n = 67/83) completed treatment in prison, and the rest were released. Of total released patients, 68% (n = 30/44) were linked to care in community, and 70% (n = 21/30) completed treatment, including 60% (n = 12/20) and 90% (n = 9/10) among those who were released before and during treatment, respectively. The overall HCV treatment uptake and completion were 89% (n = 103/116) and 85% (n = 88/103), respectively. From people who completed treatment, 43% (n = 38/88) attended for response assessment and all were cured (SVR12 = 100%). CONCLUSIONS: Integrated HCV care models are highly effective and can be significantly strengthened by post-release interventions. The close collaboration of community and prison healthcare systems is crucial to promote high levels of treatment adherence. Future studies should investigate the predictors of engagement with HCV care following release.

Global prevalence of HCV and/or HBV coinfections among people who inject drugs and female sex workers who live with HIV/AIDS: a systematic review and meta-analysis.

Coinfections of hepatitis C virus (HCV) and/or hepatitis B virus (HBV) with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) are associated with high morbidity and mortality and poor prognosis. The main objective of this study was to evaluate the prevalence of HCV and/or HBV coinfections among people who inject drugs (PWID) and female sex workers (FSWs) who live with HIV/AIDS worldwide. Data sources were searched from January 2008 to October 2018 in different databases, including PubMed, Scopus, Web of Science, Embase, and Ovid. Data were analyzed in Stata 14 software using the Metaprop command. The results showed that the prevalence of HCV among PWID and FSWs with HIV/AIDS was 72% (95% CI: 59%-83%) and 40% (95% CI: 0%-94%), respectively. The prevalence of HBV among PWID and FSWs with HIV/AIDS was 8% (95% CI: 5%-13%) and 2% (95% CI: 0%-7%), respectively, and the prevalence of HCV/HBV in PWID with HIV/AIDS was 11% (95% CI: 7%-15%). The highest prevalence of HCV was observed in PWID in the Eastern Mediterranean and Europe regions, and the lowest was observed in the Africa region. The South-East Asia region had the highest prevalence of HBV among PWID, and the Africa region had the lowest prevalence. The high prevalence of HCV coinfection among PWID and FSWs with HIV/AIDS was an alarming health problem and requires appropriate interventions. Therefore, considering that these populations are key populations for HCV elimination, it is recommended to screen them regularly for HCV. In addition, harm reduction and HBV vaccination should be carefully considered.

Systematic Review and Meta-Analysis of Global Prevalence of HBsAg and HIV and HCV Antibodies among People Who Inject Drugs and Female Sex Workers.

The main objective of this study was to evaluate the prevalence of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), hepatitis C virus (HCV) and hepatitis B virus (HBV) and their co-infections among people who inject drugs (PWID) and female sex workers (FSWs). Data sources were searched from January 2008 to October 2018 in different databases. Data were analyzed in Stata 16 software using the Metaprop command. The results showed that the prevalence of HIV, HCV and HBV among PWID was 15%, 60% and 6%, respectively. The prevalence of HIV, HCV and HBV among FSWs was 5%, 1% and 3%, respectively. The prevalence of HIV/HCV, HIV/HBV, HCV/HBV and HIV/HCV/HBV co-infections among PWID was 13%, 2%, 3% and 2%, respectively. The prevalence of HIV/HCV and HIV/HBV co-infections among FSWs was 3% and 1%, respectively. The results show that the prevalence of HCV and HIV infections in PWID and the prevalence of HIV in FSWs is higher than their prevalence in the general population. Interventions for the prevention of HIV and HCV in PWID appear to be poor, and may not be sufficient to effectively prevent HIV and HCV transmission.