Socioeconomic stability is associated with lower injection frequency among people with distinct trajectories of injection drug use.

BACKGROUND: Little is known about how socioeconomic circumstances relate to injection frequencies among people who inject drugs (PWID) with diverse trajectories of injection. We aimed to characterize trajectories of injection drug use in a community-based sample of PWID over 7.5 years and to investigate the extent to which two modifiable factors reflecting socioeconomic stability-stable housing and stable income-relate to injection frequencies across distinct trajectories. METHODS: HEPCO is an open, prospective cohort study of PWID living in Montréal with repeated follow-up at three-month or one-year intervals. Self-reported data on injection frequency, housing and income are collected at each visit. Injection frequency was defined as the number of injection days (0-30), reported for each of the past three months. Using group-based trajectory modeling, we first estimated average trajectories of injection frequency. Then, we estimated the trajectory group-specific average shift upward or downward associated with periods of stable housing and stable income relative to periods when these conditions were unstable. RESULTS: Based on 19,527 injection frequency observations accrued by 529 participants followed over 2011-2019 (18.3% female, median age: 41), we identified five trajectories of injection frequency: three characterized by sustained injection at different frequencies (28% infrequent; 19% fluctuating; 19% frequent), one by a gradual decline (12%), and another by cessation (28%). Periods of stable housing and stable income were each independently associated with a lower injection frequency, on average, in all five trajectory groups (2.2-7.5 fewer injection days/month, depending on the factor and trajectory group). CONCLUSION: Trajectories of injection drug use frequency were diverse and long-lasting for many PWID. Despite this diversity, socioeconomic stability was consistently associated with a lower injection frequency, emphasizing the close relationship between access to fundamental necessities and injection patterns in all PWID, irrespective of whether they are on a path to cessation or sustained injecting.

Injecting frequency trajectories and hepatitis C virus acquisition: Findings from a cohort of people who inject drugs in Montréal, Canada.

BACKGROUND: Frequent injecting increases hepatitis C (HCV) acquisition risk among people who inject drugs (PWID). However, few studies have examined how temporal fluctuations in injecting frequency may effect HCV infection risk. Thus, this study examined HCV incidence according to injecting frequency trajectories followed by PWID over one year in Montréal, Canada. METHODS: At three-month intervals from March 2011 to June 2016, HCV-uninfected PWID (never infected or cleared infection) enrolled in the Hepatitis Cohort (HEPCO) completed interviewer-administered questionnaires and HCV testing. At each visit, participants reported the number of injecting days (0-30 days) for each of the past three months. In previous work, using group-based trajectory modeling, we identified five injecting frequency trajectories followed by participants over one year (months 1-12 of follow-up), including sporadic, infrequent, increasing, decreasing, and frequent injecting. In this study, we estimated group-specific HCV incidence (months 1-63 of follow-up) using posterior probabilities to assign participants to their most likely trajectory group. RESULTS: Of 386 participants (mean age=40, 82% male, 48% never HCV-infected), 72 acquired HCV during 893 person-years of follow-up. HCV incidence for the whole study sample was 8.1 per 100 person-years (95%CI=6.4-10.1). Trajectory group-specific HCV incidences were highest for those injecting drugs with decreasing (23.9, 14.4-37.5) or increasing frequency (16.0, 10.1-24.3), intermediate for those injecting at consistently high frequency (10.2, 5.4-17.8), and lowest for those injecting infrequently (3.9, 2.2-6.5) or sporadically (4.3, 2.2-7.6). CONCLUSION: Results suggest that PWID at highest HCV risk are those injecting at high frequency, either transitorily (increasing, decreasing injecting) or consistently (frequent injecting). This study highlights changes in injecting frequency as a potentially important dimension to consider among the factors leading to HCV acquisition. Clinical and public health interventions tailored to PWID with different injecting frequency profiles may contribute to HCV prevention.

Associations between housing stability and injecting frequency fluctuations: findings from a cohort of people who inject drugs in Montréal, Canada.

BACKGROUND: The relationship between housing stability and drug injecting is complex, as both outcomes fluctuate over time. The objectives were to identify short-term trajectories of housing stability and injecting frequency among people who inject drugs (PWID) and examine how patterns of injecting frequency relate to those of housing stability. METHODS: At three-month intervals, PWID enrolled between 2011 and 2016 in the Hepatitis Cohort completed an interviewer-administered questionnaire and were tested for hepatitis C and HIV infections. At each visit, participants reported, for each of the past three months, the accommodation they lived in the longest (stable/unstable) and the number of injecting days (0-30). Group-based dual trajectory modeling was conducted to identify housing stability and injecting frequency trajectories evolving concomitantly over 12 months and estimate the probabilities of following injecting trajectories conditional upon housing trajectories. RESULTS: 386 participants were included (mean age 40.0, 82 % male). Three housing stability trajectories were identified: sustained (53 %), declining (20 %), and improving (27 %). Five injecting frequency trajectories were identified: sporadic (26 %), infrequent (34 %), increasing (15 %), decreasing (11 %), and frequent (13 %). PWID with improving housing were less likely to increase injecting (8 %) compared to those with sustained (17 %) or declining housing (17 %). CONCLUSIONS: Improving housing was associated with a lower probability of increasing injecting compared to declining housing, while sustained housing stability was associated with a higher probability of increasing injecting compared to improving housing. Therefore, policies to improve PWID's access to stable housing are warranted and may reduce, to some extent, drug injecting and related harms.

Association between mental health service utilisation and sharing of injection material among people who inject drugs in Montreal, Canada.

BACKGROUND: High-risk injection behaviors are associated with high prevalence of mental health problems among people who inject drugs (PWID). However, whether the use of mental health services is associated with lower risk of sharing injection material remains undetermined. This study aims to examine the association between mental health service utilisation and receptive sharing risk, and determine the potential modifying effect of psychological distress on this association. METHODS: Participants answered an interviewer-administered questionnaire at 3-month intervals gathering information on sociodemographic characteristics, substance use and related behaviors, services utilisation and significant mental health markers. Relationship between the use of mental health services and receptive sharing was modeled using the generalized estimating equation (GEE), controlling for age at baseline, gender, and other potential confounders. Psychological distress was estimated using the Kessler Psychological Distress Scale (K10). Effect modification was investigated by adding an interaction term in the univariate GEE analysis. RESULTS: 358 participants contributed to 2537 visits (median age 40.3, 82% male). Mental health service utilisation was reported in 631 visits (25%), receptive sharing in 321 visits (13%) and severe psychological distress in 359 visits (14%). In multivariate GEE analyses, a significant association was identified between receptive sharing and the use of mental health services (aOR = 0.69; 95% CI = 0.50-0.94). We found no evidence of effect modification by psychological distress. CONCLUSION: Among PWID, mental health service utilisation was associated with lower likelihood of receptive sharing, regardless of level of psychological distress. These findings should be taken into account when designing harm reduction strategies for this population.

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.

6th Canadian Symposium on Hepatitis C Virus: Delivering a cure for hepatitis C infection-What are the remaining gaps?

Estimates are that more than 250,000 people in Canada are chronically infected with hepatitis C virus (HCV), and many more are unaware of their infection status. If untreated, chronic HCV infection can lead to cirrhosis and subsequent complications such as hepatocellular carcinoma. The Canadian Network on Hepatitis C, supported by the Public Health Agency of Canada and the Canadian Institutes of Health Research, has been committed to the scientific study of chronic hepatitis C and to supporting the advocacy work to improve diagnosis and access to HCV care in Canada. Although the treatment of HCV infection has been greatly advanced with direct-acting antivirals, with cure rates as high as 95%, many challenges remain in the implementation of HCV care. These issues include the lack of an effective vaccine, infection screening, treatment failure or resistance, post-cure health issues, limitations of treatment access despite increased provincial subsidization, complex needs of at-risk populations (ie, injection drug users, societal obstacles). At the 6th Canadian Symposium on HCV in March 2017, the theme "Delivering a Cure for Hepatitis C Infection: What Are the Remaining Gaps?" provided a framework in which basic scientists, clinicians, epidemiologists, social scientists, and community members interested in HCV research in Canada could showcase how they are working to address these ongoing challenges.

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.

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.

Depression, Anxiety, and Stress Among People With Chronic Hepatitis C Virus Infection and a History of Injecting Drug Use in New South Wales, Australia.

OBJECTIVE: The aims of this study were to assess symptoms of depression, anxiety, and stress and associated sociodemographic factors among people living with chronic hepatitis C virus (HCV) infection with a history of injecting drug use and to assess the association between symptoms of depression, anxiety, or stress and HCV treatment intent, specialist assessment, or treatment uptake. METHODS: The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings was an observational cohort study evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from 9 community health centers and opioid substitution therapy (OST) clinics (New South Wales, Australia). Symptoms were assessed using the Depression Anxiety Stress Scales (DASS-21). Analyses were performed using logistic regression. RESULTS: Among 415 participants (mean age 41 years, 71% male), 47%, 52%, and 36% demonstrated moderate to extremely severe symptoms of depression, anxiety, and stress, respectively. In adjusted analyses, depression symptoms were associated with recent injecting drug use [adjusted odds ratio (aOR) 1.63, 95% confidence interval (CI) 1.07-2.49), whereas stress symptoms were associated with unemployment (aOR 2.99, 95% CI 1.09-8.15) and not living with a spouse or other relatives/friends (aOR 1.55, 95% CI 1.01-2.39). Symptoms of depression, anxiety, or stress or having a history of treated mental illness were not independently associated with HCV treatment intent, specialist assessment, or treatment uptake. CONCLUSIONS: Findings suggest a need for improved interventions and care regarding mental health among people living with chronic HCV with a history of injecting drug use, but suggest that symptoms of depression, anxiety, and stress should not be immediate contraindications to HCV assessment and treatment.

The effect of social functioning and living arrangement on treatment intent, specialist assessment and treatment uptake for hepatitis C virus infection among people with a history of injecting drug use: The ETHOS study.

BACKGROUND: The objective was to assess social functioning and its association with treatment intent, specialist assessment and treatment uptake for hepatitis C virus (HCV) infection among people with a history of injecting drug use. METHODS: ETHOS is a prospective observational cohort evaluating the provision of HCV assessment and treatment among people with chronic HCV and a history of injecting drug use, recruited from nine community health centres and opioid substitution treatment clinics (NSW, Australia). Social functioning was assessed using a short form of the Opioid Treatment Index social functioning scale. Those classified in the highest quartile (score >6) were considered having lower social functioning. Analyses were performed using logistic regression. RESULTS: Among 415 participants (mean age 41 years, 71% male), 24% were considered having lower social functioning, 70% had early HCV treatment intent (intention to be treated in the next 12 months), 53% were assessed by a specialist and 27% initiated treatment. Lower social functioning was independently associated with unemployment, unstable housing, recent injecting drug use and moderate to extremely severe symptoms of depression, anxiety and stress. Lower social functioning was independently associated with reduced early HCV treatment intent (aOR 0.51, 95% CI 0.30-0.84) and lower specialist assessment (aOR 0.48, 95% CI 0.29-0.79), but not HCV treatment uptake (aOR 0.76, 95% CI 0.40-1.43). Living with someone was independently associated with HCV treatment uptake (with someone and children: aOR 2.28, 95% CI 1.01-5.14; with someone and no children: aOR 2.36, 95% CI 1.30-4.31), but not early HCV treatment intent or specialist assessment. CONCLUSIONS: This study highlights the need for the development and implementation of strategies targeting people who inject drugs with lower social functioning to enhance HCV treatment intent and specialist assessment. Further, strategies to enhance social support may play a role in increasing HCV treatment uptake.

Cannabinoids reward sensitivity in a neurodevelopmental animal model of schizophrenia: a brain stimulation reward study.

The comorbidity schizophrenia and cannabis has a high prevalence. The consumption of cannabis is ten times higher among schizophrenia patients, suggesting that these patients could be differentially sensitive to its motivational effects. To study this question, we investigated the motivational effects of cannabinoid agonists using the brain stimulation reward paradigm and a neurodevelopmental model of schizophrenia: neonatal ventral hippocampus lesions (NVHL). Using the curve-shift paradigm, we first compared the effect single dose (0.75mg/kg) of amphetamine in sham and NVHL rats on reward and operant responding. Then, in different groups of NVHL and sham rats, we studied the effect of delta-9-tetrahydrocannabinnol (THC, 0.5mg/kg, i.p.) and WIN55,212-2 (WIN, 1 and 3mg/kg, i.p.) Rats were initially trained to self-administer an electrical stimulation to the posterio-medial mesencephalon. Once responding was stable, reward threshold defined as the frequency required to induce a half maximum response rate was measured before and after injection of the drug or the vehicle. Results show that amphetamine enhanced reward in sham and NVHL rats, an effect that was shorter in duration in NVHL rats. THC produced a weak attenuation of reward in sham rats while WIN produced a dose-dependent attenuation in NVHL; the attenuation effect of WIN was blocked by the cannabinoid antagonist, AM251. WIN also produced an attenuation of performance in sham and NVHL rats, and this effect was partially prevented by AM251. These results provide the additional evidence that the motivational effect of cannabinoids is altered in animals with a schizophrenia-like phenotype.

Opposite modulation of brain stimulation reward by NMDA and AMPA receptors in the ventral tegmental area.

Previous studies have shown that blockade of ventral tegmental area (VTA) glutamate N-Methyl-D-Aspartate (NMDA) receptors induces reward, stimulates forward locomotion and enhances brain stimulation reward. Glutamate induces two types of excitatory response on VTA neurons, a fast and short lasting depolarization mediated by α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors and a longer lasting depolarization mediated by NMDA receptors. A role for the two glutamate receptors in modulation of VTA neuronal activity is evidenced by the functional change in AMPA and NMDA synaptic responses that result from repeated exposure to reward. Since both receptors contribute to the action of glutamate on VTA neuronal activity, we studied the effects of VTA AMPA and NMDA receptor blockade on reward induced by electrical brain stimulation. Experiments were performed on rats trained to self-administer electrical pulses in the medial posterior mesencephalon. Reward thresholds were measured with the curve-shift paradigm before and for 2 h after bilateral VTA microinjections of the AMPA antagonist, NBQX (2,3,-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulfonamide, 0, 80, and 800 pmol/0.5 µl/side) and of a single dose (0.825 nmol/0.5 µl/side) of the NMDA antagonist, PPPA (2R,4S)-4-(3-Phosphonopropyl)-2-piperidinecarboxylic acid). NBQX produced a dose-dependent increase in reward threshold with no significant change in maximum rate of responding. Whereas PPPA injected at the same VTA sites produced a significant time dependent decrease in reward threshold and increase in maximum rate of responding. We found a negative correlation between the magnitude of the attenuation effect of NBQX and the enhancement effect of PPPA; moreover, NBQX and PPPA were most effective when injected, respectively, into the anterior and posterior VTA. These results suggest that glutamate acts on different receptor sub-types, most likely located on different VTA neurons, to modulate reward.