Sexual behaviour as a risk factor for hepatitis C virus infection among people who inject drugs in Montreal, Canada.

Hepatitis C virus (HCV) acquisition remains high in key risk environments including injection drug use and sex between men. However, few studies examine the independent contribution of sexual behaviour to HCV acquisition among people who inject drugs (PWID). We estimated HCV incidence and examined sexual behaviour as a time-varying predictor of HCV acquisition in a prospective cohort study of PWID in Montreal (2004-2017). Initially, HCV-negative participants completed behavioural questionnaires and HCV antibody testing (6 months until 2011, 3 months thereafter). A time-updating exposure variable (no sex, opposite-sex partner only, ≥1 same-sex partner) was generated for the previous 6/3 months. Time to HCV seroconversion was examined using Cox regression analysis, adjusted for age, unstable housing and incarceration (both past 3 months), and daily, heroin, cocaine and prescription opioid injecting (all past month). Among 440 PWID (baseline: median age 33 years, 18.9% female, 1.4% HIV-positive), 156 participants seroconverted during follow-up (overall incidence rate: 11.9/100 person-years [PY]). Incidence was lowest in the no sex group (8.70 and 2.91 cases/100 PY in males and females, respectively) and highest in the ≥1 same-sex partner group (24.14 and 21.97 cases/100 PY in males and females, respectively). Among males, HCV risk was 47% lower in those reporting no sex compared to ≥1 same-sex partner (adjusted hazard ratio: 0.53, 95% confidence interval: 0.28, 0.99). In this cohort of PWID, reporting recent same-sex partners was associated with greater risk of HCV acquisition among males, necessitating targeted harm reduction strategies that consider the complex interplay of sexual and injecting risk behaviours.

Opioid agonist treatment dosage and patient-perceived dosage adequacy, and risk of hepatitis C infection among people who inject drugs.

BACKGROUND: Opioid agonist treatment is considered important in preventing acquisition of hepatitis C virus (HCV) among people who inject drugs; however, the role of dosage in opioid agonist treatment is unclear. We investigated the joint association of prescribed dosage of opioid agonist treatment and patient-perceived dosage adequacy with risk of HCV infection among people who inject drugs. METHODS: We followed prospectively people who inject drugs at risk of acquiring HCV infection (who were RNA negative and HCV-antibody negative or positive) in Montréal, Canada (2004-2017). At 6-month, then 3-month intervals, participants were tested for HCV antibodies or RNA, and completed an interviewer-administered behavioural questionnaire, reporting the following: current exposure to opioid agonist treatment (yes/no), prescribed dosage either high (methadone ≥ 60 mg/d or buprenorphine ≥ 16 mg/d) or low, and perceived dosage adequacy (adequate/inadequate). We then assigned participants to 1 of 5 exposure categories: no opioid agonist treatment, high dosage of opioid agonist treatment perceived to be adequate, high dosage perceived to be inadequate, low dosage perceived to be adequate or low dosage perceived to be inadequate. To estimate associations between categories of opioid agonist treatment dosage and incident HCV infection, we conducted Cox regression analyses, adjusting for multiple confounding factors. RESULTS: Of 513 participants (median age 35.0 yr, 77.6% male), 168 acquired HCV over 1422.6 person-years of follow-up (incidence 11.8/100 person-years, 95% confidence interval [CI] 10.1-13.7). We observed a gradient in the relative risks of HCV infection across categories of opioid agonist treatment dosage. Compared with people who inject drugs not receiving opioid agonist treatment, adjusted hazard ratios were 0.43 (95% CI 0.23-0.84) for those receiving high dosages perceived to be adequate, 0.61 (95% CI 0.25-1.50) for those receiving high dosages perceived to be inadequate, 1.22 (95% CI 0.74-2.00) for those receiving low dosages perceived to be adequate and 1.94 (95% CI 1.11-3.39) for those receiving low dosages perceived to be inadequate. INTERPRETATION: Risk of HCV infection varies considerably according to dosage of opioid agonist treatment and patient-perceived adequacy, with associations indicating both protective and harmful effects relative to no exposure to opioid agonist treatment.

Association between binge drug use and suicide attempt among people who inject drugs.

BACKGROUND: People who inject drugs (PWID) have an elevated risk of suicide attempt. Although different substances are associated with suicide attempt, the overall risk posed by binge behavior, a high-risk pattern of drug use, remains unclear. The objective of this study is to assess the association between binge drug use and suicide attempt in a prospective cohort of PWID in Montreal, Canada. METHODS: Participants answered a biannual interviewer-administered questionnaire compiling information on sociodemographics, pattern of substance use (cocaine, amphetamine, opioids, sedative-hypnotics, alcohol, and cannabis), and psychosocial stressors and related markers. The relationship between suicide attempt and binge behavior was modeled using generalized estimating equations (GEEs), controlling for type and pattern of substance use, sociodemographic characteristics, and significant mental health markers. RESULTS: Among 1240 participants (mean age ± SD: 38.2 ± 9.8) at baseline, 222 (17.9%) reported binge during the past 6-months. PWID reporting binge were significantly younger (P < .001), less educated (P = .012), less likely male (P = .047), and had shorter history of injection (P < .001). In addition, they were younger at first injection (P = .014), reported higher rates of prostitution and psychological disorders (P = .003), and were more likely to use other drugs except cannabis and alcohol. Binge was independently associated with attempted suicide in the GEE multivariate model (adjusted odds ratio [aOR 95% CI] = 1.91 [1.38-2.65], P < .001). CONCLUSIONS: Among PWID at high risk of suicide attempt, those who binge represent a particularly vulnerable subgroup. Although the exact mechanisms underlying this finding remain unresolved, several hypothesis pertaining to the neurobiological and psychosocial consequences of binge, as well as common personality traits, warrant further investigations.

Sustained drug use changes after hepatitis C screening and counseling among recently infected persons who inject drugs: a longitudinal study.

BACKGROUND: Notification of hepatitis C virus (HCV) positive status is known to have short-term impacts on subsequent alcohol, drug use and injection behaviors among persons who inject drugs (PWID). It remains to be established whether postscreening behavioral changes extend over time for PWID and whether screening test notification has behavioral impacts among HCV-negative PWID. This study sought to longitudinally assess substance use and injection behaviors after HCV status notification among HCV seroconverters and HCV-negative PWID. METHODS: Initially HCV-seronegative PWID (n = 208) were followed prospectively between 2004 and 2011 in Montreal, Canada. Semiannual screening visits included blood sampling and an interview-administered questionnaire assessing substance use and injection behaviors. Multivariable generalized estimating equation analyses were conducted to assess substance use and behavior changes over time and compare changes between HCV seroconverters and HCV-seronegative participants while adjusting for baseline characteristics. RESULTS: Of the 208 participants (83% male; mean age, 34.7 years, mean follow-up time, 39 months), 69 (33.2%) seroconverted to HCV. A linear decrease in syringe sharing behavior was observed over time after HCV and status notification, whereas a 10% decrease for each additional 3 months of follow-up was observed for injection cocaine and heroin use among HCV seroconverters but not among HCV-seronegative PWID (P < .05). No significant changes were observed in alcohol use. CONCLUSIONS: Our results indicate that notification of HCV-positive status is associated with reduced injection drug use among seroconverters. Among PWID deemed seronegative after screening, there is no sustained trend for change in risk behavior.

Plasma interferon-gamma-inducible protein-10 (IP-10) levels during acute hepatitis C virus infection.

UNLABELLED: Systemic levels of interferon-gamma-inducible protein-10 (IP-10) are predictive of treatment-induced clearance in chronic hepatitis C virus (HCV). In the present study, factors associated with plasma IP-10 levels at the time of acute HCV detection and the association between IP-10 levels and spontaneous clearance were assessed in three cohorts of acute HCV infection. Among 299 individuals, 245 (181 male, 47 human immunodeficiency virus-positive [HIV+]) were HCV RNA+ at acute HCV detection. In adjusted analysis, factors independently associated with IP-10 levels ≥150 pg/mL (median level) included HCV RNA levels >6 log IU/mL, HIV coinfection and non-Aboriginal ethnicity. Among 245 HCV RNA+ at acute HCV detection, 214 were untreated (n = 137) or had persistent infection (infection duration ≥26 weeks) at treatment initiation (n = 77). Spontaneous clearance occurred in 14% (29 of 214). Individuals without spontaneous clearance had significantly higher mean plasma IP-10 levels at the time of acute HCV detection than those with clearance (248 ± 32 versus 142 ± 22 pg/mL, P = 0.008). The proportion of individuals with spontaneous clearance was 0% (0 of 22, P = 0.048) and 16% (27 of 165) and in those with and without plasma IP-10 levels ≥380 pg/mL. In adjusted analyses, favorable IL28B genotype was associated with spontaneous clearance, while higher HCV RNA level was independently associated with lower odds of spontaneous clearance. CONCLUSION: High IP-10 levels at acute HCV detection were associated with failure to spontaneously clear HCV. Patients with acute HCV and high baseline IP-10 levels, particularly >380 pg/mL, should be considered for early therapeutic intervention, and those with low levels should defer therapy for potential spontaneous clearance. (HEPATOLOGY 2013;).

Gender, sexual orientation identity, and initiation of amphetamine injecting among people who inject drugs: Examination of an expanding drug era in Montreal, Canada, 2011-19.

BACKGROUND: Amphetamine injection is expanding in North America and has been associated with male homosexuality among people who inject drugs (PWID). Applying subcultural evolution theory, we examined overall and gender-stratified trends in amphetamine injection and assessed sexual orientation as a gender-specific predictor of initiation among PWID in Montreal, Canada. METHODS: Data were from HEPCO, an open prospective cohort of PWID. Gender and sexual orientation were self-identified at enrolment. Interviewer-administered questionnaires at three-monthly (HCV RNA-negative participants) or yearly (RNA-positive) intervals captured past three-month amphetamine injection and covariates. Annual prevalence and linear trends in amphetamine injection were estimated using GEE. Incidence was computed among naïve individuals and hazard ratios for initiation estimated using gender-stratified, time-varying Cox regression models. RESULTS: 803 participants contributed 8096 observations between March 2011 and December 2019. Annual prevalence of amphetamine injecting increased from 3.25% [95%CI: 2.06-4.43%] to 12.7% [9.50-16.0] (trend p<0.001). Bivariate Cox regression models suggested similar and divergent predictors of initiation by gender. Incidence was 3.27 per 100 person-years [95%CI: 2.51-4.18] among heterosexual men, 7.18 [3.50-13.2] among gay/bisexual men, 1.93 [0.78-4.02] among heterosexual women and 5.30 [1.69-12.8] among gay/bisexual women. Among men, gay/bisexual identity doubled risk of initiation after adjusting for age, ethnicity, calendar year (aHR 2.16 [1.07-4.36]) and additional covariates (2.56 [1.24-5.30]). Among women, evidence for an association with gay/bisexual identity was inconclusive (aHR 2.63 [0.62-11.2]) and sample size precluded further adjustment CONCLUSIONS: Prevalence of amphetamine injection among PWID increased four-fold from 2011 to 2019, with elevated risk of initiation in gay and bisexual men.

HCV treatment initiation in the era of universal direct acting antiviral coverage - Improvements in access and persistent barriers.

BACKGROUND: Barriers to HCV treatment initiation persisted after the introduction of direct-acting antivirals (DAAs) in Canada among people who inject drugs (PWID); whether DAA universal coverage lifted these barriers remain unknown. We assessed the evolution of HCV treatment initiation and associated factors among PWID in Montreal, Canada, comparing eras of IFN-based regimens (2011-2013), of DAA restricted access (2014-02/2018), and universal coverage (03/2018-03/2020). METHODS: We included chronically HCV-infected participants followed in a community-based PWID cohort in Montreal, Canada between 2011 and 03/2020 and collected data at 3-month intervals. Time-updated Cox regressions were conducted to examine 9 variables of interest associated with treatment initiation overall and for each of the three eras. RESULTS: Of 276 participants, 126 initiated treatment during follow-up. Yearly initiation increased from 3% in 2011 to 19% in 2016, and 54% in 2018. PWID aged >40 (vs. ≤40) were twice as likely to initiate treatment in 2014-02/2018 (HR: 2.02 95%CI: [1.24-3.28]) but not in other periods (2011-2013: 0.55 [0.25-1.22]; 03/2018-03/2020: 1.14 [0.59-2.22])). Odds of initiation were lower for men than women in all periods, with women three times more likely to be treated under universal coverage (0.30 [0.11-0.77] vs 2011-2013: 0.67 [0.25-1.78] and 2014-02/2018: 0.75 [0.42-1.35]). Recent incarceration was negatively associated with initiation throughout all periods (2011-2013: 0.57 [0.13-2.43]; 2014-03/2018: 0.39 [0.17-0.91]; 03/2018-03/2020: 0.25 [0.07-0.83]). Barriers associated with high injection frequency appear to have diminished since DAA introduction (2014-02/2018: 0.71 [0.42-1.20]; 03/2018-03/2020: 1.05 [0.52-2.11] vs. 2011-2013: 0.26 [0.08-0.88]). Contact with a primary care physician and engagement in opioid agonist therapy were positively associated with treatment initiation, though estimates were attenuated under universal coverage relative to previous eras. CONCLUSION: Treatment initiation rates have increased since the introduction of universal DAA coverage, though barriers such as incarceration persist.

Determinants of lymph node count in endometrial cancer surgical staging.

OBJECTIVE: Lymphadenectomy is a fundamental procedure in gynecologic oncology, but there is an ongoing debate concerning its indication in endometrial cancer. Lymph node (LN) count has been used as a surrogate marker for quality of staging in endometrial cancer. Because of variability in reported LN counts in the literature and within our practice, we aimed to better understand the factors that influence the final LN count in endometrial cancer staging. METHODS: We conducted a retrospective case study of patients with endometrial cancer who underwent surgical staging at our institution between April 1, 2005, and February 3, 2007. Linear regression was used to determine the association between LN count and a series of predictor variables. RESULTS: Of 131 patients, 100 patients (76%) had stage I disease and 9 patients (7%) had LN metastasis. The mean (SD) LN count was 9.5 (7.8). We found no significant difference in LN count according to age, tumor histology, stage, or surgeon. Lymph node count decreased by 1 for each 5-unit (kg/m(2)) increase in body mass index (coefficient, -0.2; P = 0.038). The strongest predictor associated with LN count was the pathologist, with 2 groups of pathologists counting an average 7.7 (P < 0.001) and 6.42 (P = 0.001) fewer LNs per case compared to the referent group. CONCLUSIONS: Our study confirms that LN count varies markedly. Although not the only contributor, the pathologist, we found, was the most significant determining factor in LN count variation. This highlights the need to exercise caution when drawing conclusions from published LN counts in endometrial cancer research.

Trends in human immunodeficiency virus incidence and risk behavior among injection drug users in montreal, Canada: a 16-year longitudinal study.

The authors sought to investigate trends in the incidence of human immunodeficiency virus (HIV) infection, evaluate changes in risk behavior, and assess associations between syringe access programs and HIV seroconversion among injection drug users (IDUs) in Montreal, Canada, who were recruited and followed for a prospective cohort study between 1992 and 2008. Methods included Kaplan-Meier survival analysis and time-varying Cox regression models. Of 2,137 HIV-seronegative IDUs at enrollment, 148 became HIV-positive within 4 years (incidence: 3.3 cases/100 person-years; 95% confidence interval: 2.8, 3.9). An annual HIV incidence decline of 0.06 cases/100 person-years prior to 2000 was followed by a more rapid annual decline of 0.24 cases/100 person-years during and after 2000. Behavioral trends included increasing cocaine and heroin use and decreasing proportions of IDUs reporting any syringe-sharing or sharing a syringe with an HIV-positive person. In multivariate analyses, HIV seroconversion was associated with male gender, unstable housing, intravenous cocaine use, and sharing syringes or having sex with an HIV-positive partner. Always acquiring syringes from safe sources conferred a reduced risk of HIV acquisition among participants recruited after 2004, but this association was not statistically significant for participants recruited earlier. In conclusion, HIV incidence has declined in this cohort, with an acceleration of the reduction in HIV transmission after 2000.

Association of fast-food restaurant and fruit and vegetable store densities with cardiovascular mortality in a metropolitan population.

Most studies that link neighbourhoods to disease outcomes have represented neighbourhoods as area-level socioeconomic status. Where objective contextual attributes of urban environments have been measured, few studies of food availability have evaluated mortality as an outcome. We sought to estimate associations between the availability of fast-food restaurants (FFR), fruit and vegetable stores (FVS), and cardiovascular mortality in an urban area. Food business data were extracted from a validated commercial database containing all businesses and services in the Montréal Census Metropolitan Area (MCMA). Mortality data (1999-2003) were obtained for the MCMA (3.4 million residents). Directly standardised mortality rates for cardiovascular deaths (n = 30,388) and non-cardiovascular deaths (all causes - cardiovascular deaths) (n = 91,132) and FFR and FVS densities (n/km²) were analysed for 845 census tracts. Generalised additive models and generalised linear models were used to analyse food source-mortality relationships. FVS density was not associated with cardiovascular or non-cardiovascular mortality (relative risk (RR) = 1.02, 95% confidence interval (CI): 0.76, 1.36, and RR = 1.14, 95% CI: 0.87, 1.50, respectively). Higher FFR density was associated with mortality in bivariate and multivariable analyses. Relative risks of death (95% CI) per 10% increase in FFR density were similar for both cardiovascular and non-cardiovascular mortality: 1.39 (1.19, 1.63) and 1.36 (1.18, 1.57), respectively, accounting for socio-demographic covariates. FFR density is associated with cardiovascular mortality but this relationship is no different in magnitude than that for non-cardiovascular mortality. These results together with null associations between FVS density and mortality do not support a major role for food source availability in cardiovascular outcomes.

Cannabis use correlates of syringe sharing among injection drug users.

This study examines whether the relation between acute cannabis use and syringe sharing during single injection days is similar among regular and nonregular users, participating in a cohort study of injection drug users in Montréal, Canada. 236 (36.6%) subjects were classified as regular cannabis users (RCUs), 227 (35.2%) as nonregular cannabis users (NRCUs), and 181 (28.1%) were abstinent. Cannabis use during a single injection day was associated with a fivefold increased risk of sharing (OR 4.92; 1.83-13.22) in NRCUs compared to RCUs. Our results indicate that cannabis use history should be considered when evaluating its potential effect on risk-taking behaviors.

Sex, age, deprivation and patterns in life expectancy in Quebec, Canada: a population-based study.

BACKGROUND: Little research has evaluated disparities in life expectancy according to material deprivation taking into account differences across the lifespan between men and women. This study investigated age- and sex-specific life expectancy differentials related to area-level material deprivation for the province of Québec, Canada from 1989-2004. METHODS: Age- and sex-specific life expectancy across the lifespan was calculated for three periods (1989-1992, 1995-1998, and 2001-2004) for the entire Québec population residing in 162 community groupings ranked according to decile of material deprivation. Absolute and relative measures were calculated to summarize differences between the most and least deprived deciles. RESULTS: Life expectancy differentials between the most and least deprived deciles were greatest for men. Over time, male differentials increased for age 20 or more, with little change occurring at younger ages. For women, differentials increased across the lifespan and were comparable to men at advanced ages. Despite gains in life expectancy among men relative to women, differentials between men and women were greater for most deprived relative to least deprived deciles. CONCLUSIONS: Similar to the US, differentials in life expectancy associated with area-level material deprivation increased steadily in Québec from 1989-2004 for males and females of all ages. Differentials were comparable between men and women at advanced ages. Previous research indicating that life expectancy differentials between most and least deprived areas are greater in men may be due to a focus on younger age groups.

Harm Reduction Coverage and Hepatitis C Incidence: Findings From a Cohort of People Who Inject Drugs.

INTRODUCTION: Needle and syringe programs and opioid agonist therapy are essential for harm reduction among people who inject drugs. Few studies assess their combined potential in preventing hepatitis C virus infection. No studies have assessed whether they perform similarly among individuals at risk of primary and recurrent infection. This study aimed to estimate the rates of hepatitis C virus acquisition according to harm reduction coverage among hepatitis C virus-naive and previously infected people who inject drugs in Montreal, Canada. METHODS: This prospective cohort study involved regular interviews and hepatitis C antibody and RNA testing (data collection: 2010-2017, analysis: 2018). Opioid agonist therapy coverage was defined by current dose: high (≥60 mg/day methadone, ≥16 mg buprenorphine), low, or none. Complete needle and syringe program coverage was defined as exclusively reporting safe needle and syringe sources (past 6 or 3 months). Combined coverage was defined as full (high-dose agonist/complete needle/syringe coverage), minimal (low-dose agonist/incomplete needle/syringe coverage), and partial (remaining combinations). Cox regression models were fit. RESULTS: A total of 106 events were observed over 1,183.1 person-years for primary and recurrent incidence rates of 10.6 (95% CI=8.0, 13.8) and 7.6 (95% CI=5.6, 9.9) per 100 years, respectively. High-dose opioid agonist therapy was associated with a 77% reduction in hepatitis C virus acquisition (hazard ratio=0.23, 95% CI=0.10, 0.50) compared with not receiving opioid agonist therapy. Needle and syringe coverage was not associated with infection rates. Estimates considering their combination reflected opioid agonist therapy coverage. Associations were similar among hepatitis C virus-naive and previously infected people who inject drugs. CONCLUSIONS: High-dose opioid agonist therapy seems particularly important to reduce drug-related harms among hepatitis C virus-naive and previously infected people who inject drugs in Montreal.

Estimating the contribution of stimulant injection to HIV and HCV epidemics among people who inject drugs and implications for harm reduction: A modeling analysis.

BACKGROUND: Stimulants, such as amphetamines and cocaine, are widely injected among people who inject drugs (PWID). Systematic reviews indicate stimulant injection is associated with HIV and HCV among PWID. Using these associations, we estimated the contribution of stimulant injection to HIV and HCV transmission among PWID. METHODS: We modeled HIV and HCV transmission among PWID, incorporating excess injecting and sexual risk among PWID who inject stimulants. We simulated three illustrative settings with different stimulants injected, prevalence of stimulant injecting, and HIV/HCV epidemiology. We estimated one-year population attributable fractions of stimulant injection on new HIV and HCV infections, and impact of scaling up needle-syringe programs (NSP). RESULTS: In low prevalence settings of stimulant injection (St. Petersburg-like, where 13 % inject amphetamine), 9% (2.5-97.5 % interval [95 %I]: 6-15 %) and 7% (95 %I 4-11 %) of incident HIV and HCV cases, respectively, could be associated with stimulant injection in the next year. With moderate stimulant injection (Montreal-like, where 34 % inject cocaine), 29 % (95 %I: 19-37 %) and 19 % (95 %I: 16-21 %) of incident HIV and HCV cases, respectively, could be associated with stimulant injection. In high-burden settings like Bangkok where 65 % inject methamphetamine, 23 % (95%I:10-34%) and 20 % (95%I: 9-27%) of incident HIV and HCV cases could be due to stimulant injection. High-coverage NSP (60 %) among PWID who inject stimulants could reduce HIV (by 22-65 %) and HCV incidence (by 7-11 %) in a decade. DISCUSSION: Stimulant injection contributes substantially to HIV and HCV among PWID. NSP scale-up and development of novel interventions among PWID who inject stimulants are warranted.

The evolving drug epidemic of prescription opioid injection and its association with HCV transmission among people who inject drugs in Montréal, Canada.

AIMS: To examine temporal trends in prescription opioid (PO) injection and to assess its association with hepatitis C virus (HCV) seroconversion among people who inject drugs (PWID). DESIGN: Prospective cohort study spanning 2004 to 2016. SETTING: Montréal, Canada. PARTICIPANTS: PWID reporting injection during the past 6 months. MEASUREMENTS: PWID were recruited between 2004 and 2016. At each 3-6-month follow-up visit, participants completed interview-administered questionnaires and were tested for HCV-antibody. FINDINGS: Among 1524 PWID [83% males, mean age 38 years, standard deviation (SD) = 10, 34% (31-36) prescription opioid (PO) injection past month] included in trends analyses, PO injection use expanded between 2004 and 2009, and plateaued between 2010 and 2016 (trend tests < 0.001 and 0.335, respectively). Of the 432 HCV-seronegative PWIDs followed at least once (81% males, mean age 34, SD 9.8, 38% injection PO), 153 became HCV-antibody-positive during 1230 years of follow-up, for an incidence of 12.4 per 100 person-years [95% confidence interval (CI) = 10.6, 14.6]. PO injectors were 3.9 times more likely to seroconvert to HCV, relative to non-PO injectors. In a multivariate analysis, a stronger association between PO injection and HCV seroconversion was found post-2009 [adjusted hazard ratio (aHR) = 5.4, 95% CI = 2.7, 10.8] than before (aHR = 1.5, 95% CI = 0.9, 2.4) (P-value for interaction = 0.001). CONCLUSION: Prescription opioid injection increased among people who inject drugs in Montréal, Canada from 2004 to 2009, to reach a plateau between 2010 and 2016. The association between prescription opioid injection and HCV seroconversion was stronger during the second period than the first according to the epidemic phase.

Short and sporadic injecting cessation episodes as predictors of incident hepatitis C virus infection: findings from a cohort study of people who inject drugs in Montréal, Canada.

BACKGROUND AND AIMS: For most people who inject drugs (PWID), drug injecting follows a dynamic process characterized by transitions in and out of injecting. The objective of this investigation was to examine injecting cessation episodes of 1-3-month duration as predictors of hepatitis C virus (HCV) acquisition. DESIGN: Cohort study. SETTING: Montréal, Canada. PARTICIPANTS: A total of 372 HCV-uninfected (HCV RNA-negative, HCV antibody-positive or -negative) PWID (mean age = 39.3 years, 82% male, 45% HCV antibody-positive) enrolled between March 2011 and June 2016. MEASUREMENTS: At 3-month intervals, participants completed an interviewer-administered questionnaire and were tested for HCV particles (HCV RNA). At each visit, participants indicated whether they injected in each of the past 3 months (defined as three consecutive 30-day periods). Injecting cessation patterns were evaluated on a categorical scale: persistent injecting (no injecting cessation in the past 3 months), sporadic injecting cessation (injecting cessation in 1 of 3 or 2 of 3 months) and short injecting cessation (injecting cessation in 3 of 3 months). Their association with HCV infection risk was examined using Cox regression analyses with time-dependent covariates, including age, gender, incarceration, opioid agonist treatment and other addiction treatments. FINDINGS: At baseline, 61, 26 and 13% of participants reported persistent injecting, sporadic injecting cessation and short injecting cessation, respectively. HCV incidence was 7.5 per 100 person-years [95% confidence interval (CI) = 5.9-9.5; 916 person-years of follow-up]. In adjusted Cox models, sporadic injecting cessation and short injecting cessation were associated with lower risks of incident HCV infection compared to persistent injecting (adjusted hazard ratios = 0.56, 95% CI = 0.30-1.04 and 0.24, 95% CI = 0.09-0.61), respectively. CONCLUSION: Short and sporadic injecting cessation episodes were common among a cohort of people who inject drugs in Montréal, Canada. Injecting cessation episodes appear to be protective against hepatitis C virus acquisition, particularly when maintained for at least 3 months.

Transitioning from interferon-based to direct antiviral treatment options: A potential shift in barriers and facilitators of treatment initiation among people who use drugs?

BACKGROUND: Multiple barriers for accessing hepatitis C virus (HCV) treatment were identified during the interferon-based (IFN) treatment era for people who inject drugs (PWID). Whether these barriers persist since the introduction of IFN-free direct-acting antiviral (DAA) agents in Canada remains to be documented. This study examined temporal trends in HCV treatment initiation and associated factors during the transition from INF-based to all-oral DAA regimens. METHODS: The study population was drawn from a prospective cohort of PWID in Montreal, Canada. At three-month/one-year intervals between 2011 and 2017, participants with chronic HCV infection completed an interviewer-administered questionnaire on socio-demographic characteristics, drug use and health service utilisation, including HCV treatment. Time-updated Cox multivariate regression models, stratified by DAA + INF (2011-2013) and all-oral DAA (2014-2017) availability periods, were conducted to examine associations between time to HCV treatment initiation and associated barriers and facilitators. RESULTS: Of 308 participants (85% male, median age 42 [IQR: 33, 50]), 80 (26%) initiated HCV treatment during 915 person-years (PY). Incidence rates increased from 1.6 /100 PY (95%CI:0.9-2.6) in 2011 to 12.7 (10.6-15.1) in 2017 (p-trend = 0.0012). In multivariate analyses, visiting a primary care physician (2011-2013: aHR = 3.63[1.21-10.9]; 2014-2017: 2.52[1.10-5.77]) and frequent injection (0.23[0.05-0.99] and 0.49[0.24-0.99]) were consistently associated with treatment initiation. Participants aged >40 (2.27[1.24-4.13]), receiving opioid agonist therapy (OAT) (2.17[1.19-3.94]), and reporting prior HCV treatment (3.00[1.75-5.15]) were more likely to initiate treatment in the all-oral DAA period. CONCLUSION: Treatment initiation increased between 2011 and 2017, but still remains low among PWID. Primary care visiting was a key facilitator regardless of the period, while engagement in OAT and health services, indicated by prior HCV treatment, increased the likelihood of treatment initiation in the DAA era. These findings suggest that access to health services is essential but not enough to scale up treatment in this population.

Incarceration history and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis.

BACKGROUND: People who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess whether incarceration history elevates HIV or HCV acquisition risk among PWID. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I2 statistic and the P-value for heterogeneity. FINDINGS: We included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk [RR] 1·81, 95% CI 1·40-2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I2=63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28-2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I2=57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94-1·65) and a 21% increase in HCV (1·21, 1·02-1·43) acquisition risk. INTERPRETATION: Incarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID. FUNDING: Engineering and Physical Sciences Research Council, National Institute for Health Research, National Institutes of Health.

Short-term injection drug use changes following hepatitis C virus (HCV) assessment and treatment among persons who inject drugs with acute HCV infection.

BACKGROUND: It is unclear whether treatment and care for hepatitis C virus (HCV) infection can help people who inject drugs (PWID) modify their injection drug use behaviours. This study examined changes in injection drug use among PWID with acute HCV systematically referred for HCV clinical assessment and treatment and offered targeted health care services, over the course of one year. METHODS: The study sample included PWID with documented acute HCV infection recruited and followed-up semi-annually at least twice in IMPACT (2007-2015), a longitudinal community-based prospective study in Montréal, Canada. Following enrolment, participants with contra-indications to treatment due to severe co-morbidity were offered targeted health care services. Pegylated interferon-alpha (12-24 weeks) was offered to all other participants who did not spontaneously resolve their infection. At each study visit, data were collected on socio-demographic factors and drug use patterns. Logistic regression was used to assess changes in injection drug use at one-year follow-up. RESULTS: Of the 87 eligible participants (mean age: 35.6; 78.2% male), 21.8% received treatment [(RT), Sustained virological response: 84.2%], 25.3% spontaneously resolved their infection (SR), 14.9% had contra-indication(s) (CI) and 37.9% chose not to engage in HCV care post-diagnosis (NE). In multivariate analyses adjusting for age, gender and injection drug use at baseline, the RT [Adjusted odds ratio (AOR): 0.18; 95% Confidence interval (CI): 0.04-0.76], SR (AOR: 0.34; 95% CI: 0.08-1.40), and CI (AOR: 0.24; 95% CI: 0.05-1.22) groups were less likely to report injection drug use at follow-up relative to the NE group. CONCLUSION: PWID who received treatment, spontaneously resolved their infection or presented with treatment contra-indication(s) reported reduced injection drug use at one-year follow-up relative to those who did not engage in therapy. Findings suggest that the benefits of HCV assessment and treatment may extent to helping PWID modify their injection drug use patterns.

High hepatitis C incidence in relation to prescription opioid injection and poly-drug use: Assessing barriers to hepatitis C prevention.

BACKGROUND: Prescription opioid (PO) injection and poly-drug use have been associated with hepatitis C virus (HCV) infection among people who inject drugs (PWID). Poly-drug use is often a barrier to key HCV preventive programmes including opioid agonist treatment. The contribution of specific drug combinations to high HCV incidence in poly-drug users has not been assessed previously. Addressing this knowledge gap could enhance HCV treatment and prevention efforts. We examined the association between specific drugs and number of drugs used in addition to injected POs, and HCV seroconversion. METHODS: PWID participating in a cohort study in Montréal (HEPCO), HCV-seronegative at baseline and followed between 2004 and 2013, were included. Data were collected by interview-administered questionnaires. Blood samples were tested for HCV new infections at each 3-6 month follow-up visit. Time-varying Cox regression models were utilized. RESULTS: Of 356 participants (81.5% males; mean age: 34.7 years), 123 (34.6%) reported injected POs in the past month at baseline. In univariate analyses, recent use of the following drugs was associated with HCV seroconversion: injected POs, injected cocaine, injected heroin, non-injected tranquilisers, and smoked crack/cocaine. The relative excess risk of HCV seroconversion due to interaction (RER1HR) was the highest for co-use of injected POs with the following substances: injected cocaine (RER1HR=3.44), smoked crack/cocaine (RER1HR=1.27), and non-injected tranquilisers (RER1HR=0.8). In addition, a significant linear trend (p<0.001) towards higher risk was observed with increasing the number of these three drugs used in combination with injected POs. CONCLUSION: Specific drugs and number of drugs used in addition to injected POs play a modulating role in the risk of HCV primary infection. Poly-drug use among people who inject POs has to be addressed in order to improve harm reduction programmes and reduce HCV transmission in this high-risk population.