22 November 2018 Factors predicting usage of low dead space syringes and association with Hepatitis C prevalence amongst people who inject drugs in the UK Adam Trickey1,2, Margaret T May1,2, Vivian Hope3,4, Zoe Ward1,2, Monica Desai4, Ellen Heinsbroek4, Matthew Hickman1,2, Peter Vickerman1,2 1Bristol Medical School, University of Bristol 2NIHR Health Protection Research Unit (HPRU) for the Evaluation of Interventions 3Liverpool John Moores University 4Public Health England

People who inject drugs (PWID) and hepatitis C virus (HCV) 22 November 2018 People who inject drugs (PWID) and hepatitis C virus (HCV) People who inject drugs (PWID) are at risk of blood borne viral infections through the sharing of needles, syringes, and other injecting equipment1 There is high prevalence of these infections, such as hepatitis C virus (HCV), amongst PWID1 Needle and syringe programmes and opiate substitution therapy can decrease the risk of getting HCV2 However, modelling suggests they are not enough to reduce HCV to low levels2 So other prevention or treatment strategies are required -Mention cochrane review (platt & hickman) 1: Degenhardt, 2017. 2: Platt, 2017

Low dead space syringes (LDSS) 22 November 2018 Low dead space syringes (LDSS) Syringes with attached needles, typically have a lower ‘dead space’ and retain far less blood following an injection, than syringes with detachable needles1 Fixed needle (1ml) Low dead space syringes (LDSS) Detachable needle High dead space syringes (HDSS) 1: Zule, 2013

Low dead space syringes (LDSS) 22 November 2018 Low dead space syringes (LDSS) For PWID that share injecting equipment, using low dead space syringes (LDSS) instead of high dead space syringes (HDSS) may lead to a reduced risk of acquiring blood borne infections1 The volume of blood held in a syringe predicts: The amount of viral load transmitted2 Virus survival outside of the body2 The World Health Organization (WHO) recommends that LDSS are supplied to prevent the transmission of blood borne viruses However, evidence for a prevention benefit is limited3 1: Vickerman, 2013, 2: Gaughwin, 1991. 3: Jacka, 2013

Research into which subgroups of PWID use LDSS has been limited 22 November 2018 Research into which subgroups of PWID use LDSS has been limited Some research indicates HDSS with longer needles are required for injecting into veins around the groin1 HDSS allow replacement of needles during an injection episode1 Injecting practices differ depending on the drug2 Some older PWID inject into their groin after veins in the limbs are worn out3 Previous research indicates that groin injectors are more likely to have high risk behaviours3 Some crack users prefer wider needles – “bitty” 1: Zule, 2013, 2: Lankenau, 2004, 3: Hope, 2015

22 November 2018 Aims To investigate the predictors of LDSS use amongst PWID to gain information about how to intervene To examine whether the type of syringe used is associated with reduced risk of HCV in the UK

Dataset 2014 and 2015 Unlinked Anonymous Monitoring Survey (UAM) 22 November 2018 Dataset 2014 and 2015 Unlinked Anonymous Monitoring Survey (UAM) Annual sero-behavioural survey of PWID Recruited from centres providing drug treatment, needle and syringe programmes and outreach work Data from across England, Wales, and Northern Ireland (not Scotland) Participants answer questionnaire about their drug use behaviours and demographic information Participants provide a dried blood spot sample that was tested for HCV antibodies.

22 November 2018 LDSS data We calculated the percentage of syringes used in the past month that were LDSS or HDSS Used two questions based on self-report: “How many individual needles (including ones attached to syringes) did you get from Needle Exchanges during the last month (28 days)?” “How many of these needles were already attached to syringes (barrels)?” We excluded participants without information on LDSS use. We used multiple imputation to account for missing data in covariates.

22 November 2018 Methods To investigate which subgroups of PWID used LDSS all the time, we used: Logistic regression to estimate unadjusted odds ratios (OR) with 95% confidence intervals (CI) of 100% LDSS usage, vs 0-99% use, with demographic and injecting variables. Multivariable logistic regression with backwards selection of predictors. To investigate the relationship between LDSS use and HCV infection risk: We estimated associations of LDSS usage with HCV with and without adjusting for groin injecting – due to the correlation between HDSS use and groin injecting Using multivariable logistic regression We repeated this with an interaction term between LDSS use and groin injecting We repeated this analysis including an interaction term between LDSS use and whether a PWID recently started injecting (less than 3 years ago) – as many prevalent HCV infections will have occurred many years ago

Results – Demographics and characteristics 22 November 2018 Results – Demographics and characteristics 3,083 had injected in the previous month -> 909 (28%) excluded due to missing information on LDSS use -> 2,174 included in the analyses -> 55% always used LDSS -> 17% used both LDSS and HDSS -> 27% always used HDSS. Variable Total Number 2,174 Age (years) - Mean 37 Days injecting last month – Mean 17 Injecting duration (years) - Mean 15 Women 24% anti-HCV positive  55% Ever been in prison 70% Homeless in last year 19% Shared equipment last month 37% Injected into groin last month 40% Injected heroin last month 90% Injected crack last month 43% Injected cocaine last month 8% Injected speed last month 21%

Predictors of LDSS usage 22 November 2018 Predictors of LDSS usage Those injecting into the groin were very unlikely to use LDSS compared to those not injecting into the groin, aOR 0.14 (0.11-0.17) Injecting crack was predictive of not using LDSS, aOR 0.79 (0.63-0.98) Heroin injectors were more likely to use LDSS than non-heroin injectors, aOR 1.47 (1.04-2.08) -those using what were classified as “other” drugs within the survey were also less likely to use LDSS all the time

Regional variation Highest: West Midlands (68%) Second: London (66%) 22 November 2018 Regional variation Highest: West Midlands (68%) Second: London (66%) Lowest: East Midlands (45%)

LDSS usage and HCV 22 November 2018 Proportion of PWID with HCV, stratified by injecting duration and whether or not they always used LDSS Dark grey bars are those that use low dead space syringes all the time Light grey bars are those that don’t Prevalence of HCV increases with injecting duration

Fully adjusted without groin injecting 22 November 2018 Odds ratios (OR) of being anti-HCV positive (against negative) N=2,174. Variable Unadjusted Fully adjusted without groin injecting Fully adjusted 0-99% LDSS use 1 100% LDSS use 0.64 (0.54, 0.76) 0.77 (0.64, 0.93) 0.95 (0.77, 1.18)   Injections (every 10) per month 1.11 (0.92, 1.33) 1.10 (0.90, 1.35) 1.07 (0.87, 1.31) Shared equipment last month 1.22 (1.01, 1.46) 1.27 (1.04, 1.55) 1.30 (1.06, 1.59) Injecting duration 1.08 (1.07, 1.09) 1.07 (1.06, 1.08) Injecting crack 2.58 (2.15, 3.09) 2.23 (1.83, 2.71) 2.17 (1.78, 2.65) Injecting heroin 1.67 (1.24, 2.24) 1.20 (0.86, 1.68) 1.15 (0.82, 1.61) Injecting “other drug” 0.77 (0.54, 1.11) 0.78 (0.52, 1.17) 0.81 (0.54, 1.21) Injecting into groin 2.35 (1.96, 2.81) NA 1.67 (1.35, 2.08) Ever been in prison 2.83 (2.34, 3.42) 2.10 (1.71, 2.58) 2.04 (1.66, 2.51) Homeless in last year 1.18 (0.95, 1.47) 1.23 (0.96, 1.57) 1.20 (0.94, 1.53) -first column is the unadjusted analyses looking at the relationship between the variables and HCV -exclusive LDSS use associated with lower odds of hep c -when adjusted for other variables such as drug type and injecting duration (second column) LDSS use still associated with lower odds of HCV -however when also adjusting for groin injecting there is no association between ldss use and hcv -groin injecting is associated with higher odds of HCV -mention separate analysis looking at non groin injectors Also: The aOR of HCV infection for exclusive LDSS use (versus any HDSS use) amongst non-groin injectors was 0.86 (0.65, 1.13).

LDSS usage and HCV amongst PWID that had recently started injecting 22 November 2018 LDSS usage and HCV amongst PWID that had recently started injecting Variable Unadjusted Fully adjusted without groin injecting Fully adjusted 0-99% LDSS use & recent starter 1 100% LDSS use & recent starter 0.46 (0.26, 0.80) 0.53 (0.30, 0.95) 0.60 (0.34, 1.08)   Injections (every 10) per month 1.11 (0.92, 1.33) 1.10 (0.90, 1.35) 1.07 (0.87, 1.31) Shared equipment last month 1.22 (1.01, 1.46) 1.29 (1.05, 1.57) 1.31 (1.07, 1.61) Injecting duration 1.08 (1.07, 1.09) 1.06 (1.05, 1.08) 1.06 (1.05, 1.07) Injecting crack 2.58 (2.15, 3.09) 2.26 (1.85, 2.76) 2.20 (1.81, 2.69) Injecting heroin 1.67 (1.24, 2.24) 1.18 (0.84, 1.65) 1.13 (0.81, 1.58) Injecting “other drug” 0.77 (0.54, 1.11) 0.78 (0.52, 1.17) 0.81 (0.54, 1.22) Injecting into groin 2.35 (1.96, 2.81) NA 1.66 (1.34, 2.06) Ever been in prison 2.83 (2.34, 3.42) 2.06 (1.68, 2.53) 2.00 (1.63, 2.47) Homeless in last year 1.18 (0.95, 1.47) 1.23 (0.97, 1.58) 1.21 (0.94, 1.54) -within last 3 years -this analysis was performed as a lot of the hcv infections are probably historical and by restricting the analysis to this subset there is more chance of the behaviours at the time of hcv infection being captured in the survey -same as last table, but there is stronger evidence of reduced odss of hcv for ldss users -groin injecting is still associated with higher odds of hcv

22 November 2018 Limitations Hard to separate out effects of LDSS use and groin injecting 98% responded to the groin injecting question, but only 72% to the LDSS questions We could only examine injecting practices in the past month We were unable to determine how current injecting practices related to practice over time Do not know when participants had been infected with HCV, could have been many years ago Recall bias and social desirability considerations Some detachable needles are now low dead space, but this availability was unlikely during the study period -(social desirability) we have a variable, self-reported, on sharing equipment but this is not necessarily reliable. Andrew mcauley did a talk where he mentioned that when questioned about whether or not they shared needles most PWID would say they didn’t but then when asked to describe their last injection it turns out that they are sharing equipment -we are still debating whether the method of adjusting for groin injecting that we used is correct or whether we should use a mediation analysis, but either way the results seem to be the same that the use of syringe type does not explain many of the excess hepatitis c infections caused by groin injecting

22 November 2018 Main results Around 2/3 of our sample used LDSS every time they injected in the past month. 1/4 were not using LDSS. Geographic differences in LDSS use across the UK, possibly due to variation in provision of LDSS, and variation in the types of drugs injected Our study found an unadjusted association between LDSS use and HCV infection. Association maintained following adjustment for drug type and injecting duration These associations weakened following adjustment for injecting into the groin, which was highly correlated with HDSS use

22 November 2018 Implications To determine whether LDSS use reduces HCV infection risk it is crucial to understand the relationship with groin injecting We know more about who uses LDSS in the UK Groin injectors are a distinct subset of PWID who use HDSS with longer needles to enable injection into deep lying veins For WHO guidelines to work needles are required that meet the needs of all PWID and minimise dead space Detachable syringes with lower dead space are being developed but they still have greater dead space than LDSS The association amongst recent initiates suggests LDSS may reduce HCV infection risk but more evidence is needed to confirm this

22 November 2018 Acknowledgements No conflicts of interest.