Impact of 5 years of hepatitis C testing and treatment in the North East of England prisons

Hepatitis C virus infection (HCV) is prevalent in prisons. Therefore, effective prison HCV services are critical for HCV elimination programmes. We aimed to evaluate the efficacy of a regional HCV prison testing and treatment programme. Between July 2017 and June 2022, data were collected prospectively on HCV test offer and uptake rates, HCV Antibody (HCV‐Ab) and HCV‐RNA positivity, treatment starts and outcomes for new inmates incarcerated in three prisons. Rates of HCV‐Ab and RNA positivity at reception, incidence of new HCV infections and reinfection following treatment were determined. From a total of 39,652 receptions, 33,028 (83.3%) were offered HCV testing and 20,394 (61.7%) completed testing. Including all receptions, 24.5% of tests (n = 4995) were HCV‐Ab positive and 8.4% of tests (n = 1713) were HCV‐RNA positive. When considering the first test for each individual (median age 34 years; 88.1% male), 14.8% (n = 1869) and 7.2% (n = 905) were HCV‐Ab and HCV‐RNA positive, respectively. The incidence of new HCV‐Ab and RNA positivity was 5.1 and 3.3 per 100 person‐years, respectively. Of 1145 HCV viraemic individuals, 18 died within 6 months and 150 were rapidly transferred out of area, leaving 977 individuals with outcomes. Of these, 835 (85.5%) received antivirals and 47 spontaneously cleared the infection, leaving 95 (9.7%) untreated. 607 (72.7%) achieved SVR. 95 patients had reinfection post‐treatment (rate 10.1 cases per 100 person‐years). Testing for HCV has increased in our prisons and the majority with viraemia are initiated on antiviral treatment. Reassuringly, a significant fall in frequency of HCV‐RNA positivity at prison reception was observed suggesting progress towards HCV elimination.


| INTRODUC TI ON
Hepatitis C virus infection (HCV) is a blood borne virus (BBV) affecting an estimated 58 million individuals worldwide and is a major cause of cirrhosis and hepatocellular carcinoma. 1,2[5] Over the past decade, treatment for HCV has been revolutionised and HCV is now easily curable.Completing an 8-12 week course of once daily oral direct acting antiviral (DAA) regimen can achieve a sustained virological response (SVR = cure of HCV infection) in 95%-99% of patients. 6Achieving SVR improves survival and quality of life, as well as reducing risk of hepatic complications and hepatocellular carcinoma. 7,8e wide availability of DAA medication has enabled health services in many countries to work towards achieving the World Health Organization (WHO) goal of HCV elimination by 2030. 9More than 70,000 individuals in England have now had treatment for HCV as part of the HCV elimination programme and prevalence rates are falling. 10jecting drug use remains the most common cause of HCV acquisition in Europe, and targeting individuals with this risk factor has been the focus of much of the elimination effort.The burden of HCV is particularly high among the prison population, with rates up to 10 times higher than in the general population. 11Drug-related crime is a common reason for incarceration, with one study finding that 68% of individuals in prison had injected drugs within the past year. 12Therefore, tackling HCV in the prison setting is a vital part of the HCV elimination programme.
Universal offering of BBV testing is recommended for all individuals upon arrival to prisons in England.In 2016, a BBV testing and inreach treatment programme was introduced to prisons in North East England (NEE) and was fully operational by 2017. 13,14This service offers BBV testing for HCV, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) to all inmates at reception to prison using dry blood spot testing (DBST).Individuals who have active HCV are offered treatment with DAAs in nurse-led clinics within the prison.
Here we present a 5-year review of our prison HCV testing and treatment programme for three prisons in NEE.Our aims were to: 1. Assess the efficacy of the HCV testing programme at reception.

| ME THODS
The universal BBV testing programme offered DBST to all individuals at reception to prison.Individuals who tested positive for HCV-RNA were offered treatment with DAAs according to NHS England recommendations. 15Prior to treatment initiation, individuals received a detailed clinical assessment in hepatitis C in-reach clinics within the prison.Treatment was initiated by specialist nurses from the Newcastle upon Tyne Hospitals NHS Foundation Trust.
Between July 2017 and June 2022, data were collected prospectively by the prison service on BBV test offer and uptake rates, HCV Antibody (HCV-Ab) and HCV-RNA positivity, and HCV treatment start rates for all new inmates incarcerated in prisons in NEE.The HCV-RNA result was available within a week of the blood test being taken.The three prisons included were: HMP Durham, a category B male remand prison with a high turnover of individuals awaiting trial; HMP Northumberland, a large category C prison housing mediumsentence male inmates; and HMP Low Newton, a female prison that houses sentenced individuals and those awaiting trial.
To assess the efficacy of the HCV testing pathway in NEE prisons, we evaluated data on HCV testing offer and screening rates per quarter during the study period.The frequency of HCV at reception was determined by rates of HCV-Ab and HCV-RNA positivity.
Two approaches were used to report this: (1) Reception: refers to all new inmates at reception, irrespective of whether they have been incarcerated multiple times (i.e.some individuals may be included more than once), and (2) For all new inmates being incarcerated, as determined by their first reception to prison within the 5 year period.
HCV-Ab tests taken within 6 months of another test were excluded to avoid counting each infection episode multiple times.Data on HBV and HIV testing were also collected, but these results will not be discussed in this paper.
The results presented show analysis of data first for all new receptions to prison as described above.This includes inmates who have been tested on more than one occasion due repeated incarcerations.Following this, treatment outcomes are presented as data for individuals.
To further evaluate the effectiveness of HCV testing in prisons, we measured the proportion of inmates who had received HCV testing within the last year at two different time points, June 2022, and February 2023.In addition, we assessed the initiation and outcomes of HCV treatment in individuals with active HCV using data from our regional HCV database, HepCare.This database contains detailed information about treatment and laboratory data, including blood tests taken within the prison or at other treatment services in the region, providing real time data on treatment outcomes.Follow-up data were collected until 31st March 2023, excluding individuals who died within 6 months of the initial positive HCV-RNA test and those who were rapidly transferred out of area (OOA) with no available clinical information.
To evaluate new HCV infections, we calculated incidence rates for individuals whose initial HCV-Ab test was negative and were followed up for HCV testing over time.The incidence rate was reported as the number of new HCV infections per 100 person-years of follow-up, which included both new HCV-Ab positivity and HCV-RNA positivity.The time to infection was defined as the date of the last HCV-Ab negative test to the date of the first HCV-Ab positive test.The same process was followed with HCV-RNA positive tests.The HCV-RNA blood sample was taken on the same day as the antibody test.
We also assessed the incidence of HCV reinfection, defined as a positive HCV-RNA test after achieving SVR, which was reported as the number of cases of reinfection per 100 person-years.The time to reinfection was taken from SVR to the first positive HCV-RNA test.SVR was defined as a negative HCV-RNA test 12 weeks or more after completing antiviral treatment.Individuals who had previously achieved SVR were not included in the incidence of new HCV infections.
We conducted a 'high intensity test and treat' (HITT) events in HMP Durham in March 2023 and HMP Northumberland in May 2023 to assess the efficacy of the reception testing.These events aimed to test every inmate in the prison over a 3-day period.A multidisciplinary team planned and extensively publicised the event within the prison, and all residents regardless of their known HCV status, were offered DBST for BBV.Numbers of HCV-Ab and RNA positivity were determined, and electronic medical records were interrogated to determine if those who were tested positive for HCV-RNA were already known or were newly diagnosed cases.This event provided us with additional information on the effectiveness of our testing program and helped us identify any gaps in our testing and treatment pathways.
The χ2 test was used to compare categorical variables.This service improvement project was registered with and approved by the Newcastle upon Tyne Hospitals NHS Foundation Trust Clinical Governance Department (reference number 8083).

| Outcomes of the reception HCV testing
During the 5-year study period, there were 39,652 new receptions across the three prisons.33,028 (83.3%) of those receptions were offered HCV testing and 20,394 (61.7%) completed testing.The median age of each individual's first HCV test was 34 years (range 18-91), the majority of those individuals tested were male (88.1%, n = 11,132).
Of those new receptions, there were 12,635 individuals.
Table 1 illustrates the HCV offering and testing rates, HCV-Ab positivity and HCV-RNA positivity rates per year.The median number of HCV-RNA positive tests per year was 363.Notably, completed testing rates have increased with time and were highest in the most recent year.Moreover, the proportion of receptions who tested HCV-RNA positive decreased has fallen.
Figure 1A shows the HCV offer and testing rates over the 5year period, broken down by quarter.While testing rates decreased during the COVID-19 pandemic, HCV-Ab positivity rates increased (Figure 1B).However, testing rates have since recovered, with 79.3% of individuals having completed HCV testing in the final quarter of the study period.
Overall, the proportion of individuals with HCV-RNA positivity out of the total number screened decreased from 9% to 6% during the study period (Figure 1C).Moreover, the proportion of HCV-Ab positive individuals who were HCV-RNA positive decreased from 46% to 26% (Figure 1D).Notably, the HCV-RNA positive prevalence was higher in the female prison than in the male prisons (14.3% vs. 7.5%, p < .01).
As of June 2022, 81.0% of residents in the three prisons had been tested for HCV in the previous 12 months.In February 2023, before a high intensity test and treat (HITT) programme was completed in Durham prison, 91.0% of residents had been tested for HCV within the last 12 months and 75.0% had been tested within the last 6 months.In April 2023, prior to completing a high intensity test and treat (HITT) programme in Northumberland prison, 82% of residents had been tested for HCV within the last 12 months and 64% had been tested within the last 6 months.

| Incidence of new HCV infections and reinfections
Among the individuals who had more than one HCV test in the study period and were HCV-Ab negative on the index test (n = 10,766), 341 (3.2%) subsequently became HCV-Ab positive.Of these, 136 (39.9%) were HCV-RNA positive.The incidence of new HCV-Ab positivity and HCV-RNA positivity was 5.1 cases and 3.3 cases per 100 person-years follow-up, respectively.
Additionally, five individuals had two reinfections after achieving SVR.The rate of reinfection was 10.1 cases per 100 person-year follow-up (a total 854 person-years follow-up).

| Outcome of a HITT event at HMP Durham
In March 2023, a HITT was conducted in HMP Durham.There were 975 individuals who were eligible for HCV testing and 942 individuals (96.6%) completed testing.In total, 117 individuals (12.4%) were HCV-Ab positive, and 24 (2.5%) were HCV-RNA

| Outcome of a HITT event at HMP Northumberland
In May 2023, a HITT was conducted in HMP Northumberland.There were 1270 individuals who were eligible for HCV testing and 1260 individuals (99.2%) completed testing.139 individuals (11%) were HCV-Ab positive, and 22 (1.7%) were HCV-RNA positive.Six of the HCV-RNA positive cases were already known to be positive, two of which were already on treatment.Therefore, 16 new individuals (1.2%) were found to have active hepatitis C.
The proportion of HCV-Ab positive results within the HITT groups was lower than the overall proportion in the data set.Specifically, 9.3% of those who had only one HCV test were HCV-Ab positive, compared to 33.4% in those individuals who had two or more HCV tests.

| DISCUSS ION
Our paper reports on 5 years of testing and treatment of hepatitis C in prisons in NEE and provides insight into progress towards HCV elimination and identifies areas to improve.
The prison population has historically had a high prevalence of BBVs, and testing rates for this group have been suboptimal.However, since 'opt out' testing was recommended in English prisons in 2013, 16 the number of individuals accepting testing has gradually increased.In our current study, 83.3% of the prison population was offered testing and a total of 76.3% had testing completed in the most recent year of evaluation, which represent a substantial improvement in comparison to data collected in 2017 when only 35% accepted testing. 14r rate of testing was lower than that has been observed in a study from eight Italian prisons where 88% had testing.They used an oral saliva test for HCV Ab, which is quicker to perform than the DBST, which may explain the higher testing rate. 17In our study, 16.7% of the prison population that were not offered testing on reception.There are many reasons for this including: reduced testing at times during the COVID-19 pandemic; prisoners being received to prison at night; and the prison not having adequate staffing to run the service on some days.
The proportion of prison residents who had BBV testing within the previous year was a little higher than the rate at reception (just over 80%).This, however, remains below the target level of >95% that has been suggested to achieve 'micro-elimination' in the prison setting. 18Despite this, the HITTs conducted in HMP Durham and HMP Northumberland only found 10 (1.1%) and 16 (1.2%)new cases of HCV, respectively, which indicates that that the overall HCV testing and treatment programme is effective.Increasing reception testing to >95% and maintaining rates of testing will be challenging in high turnover prisons, particularly as rates of HCV viraemia fall.
However, achieving high testing rates and prompt initiation of antiviral treatment in the remand prisons may reduce the need for reception testing in medium and long stay prisons, particularly if HITTs have been conducted and micro-eliminated HCV in those prisons.
The rate of HCV at prison reception is likely to be a good marker of trends in HCV prevalence in the wider community.The decreasing frequency of HCV-RNA positivity at reception in our study is encouraging and suggests that we are making progress towards HCV elimination.However, there was still a high rate of HCV-RNA positivity (6%) at reception and a significant incidence of new HCV infection (5.1 and 3.3 per 100 person-years for HCV-Ab and HCV-RNA positivity, respectively) and reinfection (10.2 per 100 personyears) indicating a large burden of untreated HCV in the community.
0][21] This underscores the need for all prisons to provide good harm minimisation education to all people who inject drugs that is reinforced at the time of release.The prisons in NEE have access to opioid agonist therapy but other harm reduction initiatives such as needle syringe programmes and access to syringe cleaning equipment when released from prison are not currently available.There must be better integration between prison and community drug and alcohol support services, and improved access to needle exchange programmes, which are crucial in reducing transmission within prisons. 22milar trends have been observed in prisons elsewhere.For instance, in Australian prisons the upscale of DAA treatment has been associated with a reduced incidence of HCV. 20The SToP-C study showed a decline in re-infection rates between 2014 and 2019 from 8.31 per 100 person-years to 4.35 per 100 person-years.They also found that the incidence of re-infection decreased from 12.36 per 100 person-years to 7.27 per 100 person-years. 23Rates of HCV in prisons do vary in different countries, likely linked to the background prevalence of injecting drug use.Denmark for example, recorded much lower overall incidence of HCV infection in prison at 0.7-1.0 per 100 person years. 24erall, our findings show that a substantial proportion of individuals who tested positive for HCV-RNA within our programme received antiviral treatment, with the majority achieving SVR.Rates of treatment initiation were above the 80% target suggested by the World Health Organization that is required to achieve HCV 'elimination'. 25However, around 1 in 10 viraemic individuals did not receive treatment and we were unable to document the outcome from treatment in approximately a quarter of cases.Our treatment initiation compares favourably with the SToP-C study where 70% of eligible patients started DAAs and a similar proportion were lost to follow-up before an outcome of treatment was documented. 26tails about the circumstances of why some individuals were not treated with antivirals was not explored in the current study, but this may be due to the fact that many individuals who are incarcerated for drug-related crimes have short sentences and can be released before treatment is initiated.Currently, our pathway of testing uses DBST that needs to be analysed in a laboratory, resulting is a delay of a few days between testing and receiving the result, which may mean some patients who are released quickly do not commence treatment.To address this, we plan to introduce a point of care HCV-RNA test at reception for individuals known to be HCV-Ab positive, to speed up the time to diagnosis of HCV viraemia, which will hopefully translate into higher rates of treatment initiation.This method has been shown to increase antiviral treatment uptake and reduce time to treatment initiation. 27,28r study does have some limitations.First, our cohort included 150 individuals who tested positive for HCV but were rapidly transferred out of our region, thus we do not have information on their treatment status.Second, a significant proportion of the cohort have unknown outcomes following treatment initiation, which is likely due to individuals being released prior to documentation of a treatment outcome.Spontaneous clearance rates could not be assessed with this data as inmates could have had screening and treatment in the community after their release, which we would not account for.In addition, given this is a 'real world' study with incomplete data for many patients, we were unable to determine the nature of why some patients did not achieve SVR.This could be due to patients not completing the course of treatment, virological failure or SVR with reinfection.However, overall our results give a good overview of outcomes from a large HCV testing and treatment programme that give insights into progress towards elimination and areas to improve.

| CON CLUS ION
This work shows increasing rates of HCV testing at receptions to prison with the majority of those with HCV viraemia being initiated on antiviral treatment.Reassuringly, we have observed a significant

2 .
Determine trends in HCV infection rates.3.Assess rates of incident HCV infection and reinfection.4.Assess the frequency of antiviral treatment initiation and their outcomes.

3. 2 |
Outcomes of individuals tested for HCV Of the 12,635 individuals who completed testing, 2210 (17.5%) were found to be HCV-Ab positive and 1145 (9.1%) were HCV-RNA positive at least once.When considering only the first HCV test for each individual, 1869 (14.8%) were HCV-Ab positive and 905 (7.2%) were HCV-RNA positive.Another 240 HCV-RNA positive tests were found in those with subsequent incarcerations.

Figure 2
Figure 2 provides an overview of the outcomes of the 1145 individuals who were HCV-RNA positive following reception testing.Of these, 18 individuals were excluded as they had died within 6 months of the HCV test, and an additional 150 individuals were rapidly transferred out of area, leaving 977 individuals with available clinical information following diagnosis.Of the 977 individuals, 835 (85.5%; 73% of all 1145) received a course of antiviral treatment, while 47 individuals were not treated as they spontaneously cleared the infection.This left 95 (9.7%) of viraemic individuals who did not receive treatment in the study period.Of those treated, 607 (72.7%) achieved SVR and 42 (5%) individuals were still awaiting blood tests to determine SVR had been achieved at the time of data collection.Of the 977 individuals with outcome data, 102 (10.4%) were known to have previously received a course of treatment for HCV

F I G U R E 1
(A-D): BBV test offer and uptake rates (A), HCV Antibody (HCV-Ab) positivity rates (B), HCV-RNA positivity rates (C) and HCV RNA/Ab ratio (D) by quarter over 5 years.positive.Fourteen of the HCV-RNA positive cases were already known to be positive, thus 10 new individuals (1.1%) were found to have active hepatitis C.

F I G U R E 2
Outcomes for the individuals who were HCV-RNA positive.*Mostly because of unfinished course of treatment.