Incidence of hepatitis C virus infection in the prison setting: The SToP-C study.

People in prison are at high risk of HCV given high injecting drug use prevalence. This study evaluated HCV incidence and associated injecting drug use characteristics in prison. The SToP-C study enrolled people incarcerated in four Australian prisons. Participants were tested for HCV at enrolment and then every 3-6 months (October-2014 to November-2019). Participants eligible for this analysis included those at-risk of HCV primary infection (anti-HCV negative) or re-infection (anti-HCV positive, HCV RNA negative) with follow-up assessment. A total of 1643 eligible participants were included in analyses (82% male; median age 33 years; 30% injected drugs in prison; 1818 person-years of follow-up). Overall HCV incidence was 6.11/100 person-years (95%CI: 5.07-7.35), with higher rate of re-infection (9.34/100 person-years; 95%CI: 7.15-12.19) than primary infection (4.60/100 person-years; 95%CI: 3.56-5.96). In total population (n = 1643), HCV risk was significantly higher among participants injecting drugs in prison [vs. no injecting; adjusted hazard ratio (aHR): 10.55, 95%CI: 5.88-18.92), and those who were released and re-incarcerated during follow-up (vs. remained incarcerated; aHR: 1.60, 95%CI: 1.03-2.49). Among participants who injected recently (during past month, n = 321), HCV risk was reduced among those receiving high-dosage opioid agonist therapy (OAT), i.e. methadone ≥60 mg/day or buprenorphine ≥16 mg/day, (vs. no OAT, aHR: 0.11, 95%CI: 0.02-0.80) and increased among those sharing needles/syringes without consistent use of disinfectant to clean injecting equipment (vs. no sharing, HR: 4.60, 95%CI: 1.35-15.66). This study demonstrated high HCV transmission risk in prison, particularly among people injecting drugs. High-dosage OAT was protective, but improved OAT coverage and needle/syringe programmes to reduce sharing injecting equipment are required.

From pathology to pleasure: Reframing mechanistic studies on same-sex sexual behavior in primates.

Same-sex sexual behaviors (SSB) in primates have historically been studied as sexual perversions, evolutionary paradoxes, and hormone-driven pathologies. Researchers in recent decades have challenged these perspectives, yet some of the original biases still linger. In this paper, we examine how the study of endocrinological mechanisms in SSB has been influenced by the historical framework of pathology. Societal attitudes and cultural conceptions of human sexuality have led researchers to study SSB in primates as the outcome of "abnormal" processes of "feminization" or "masculinization" of sexual behavior. Here, we argue for a renewed attention to other areas of inquiry regarding the relationship between hormones and SSB, such as the role of pleasure. We briefly review how current knowledge on the neuroendocrinology of pleasure in nonhuman primates may relate to the expression of SSB and highlight oxytocin and dopamine as potentially fruitful areas for future research. We argue that future studies on SSB in primates would benefit from 1) acknowledging how the historical study of SSB as a pathology has shaped mechanistic studies and 2) studying SSB with the same holistic approach as is taken with different-sex sexual behavior (DSB).

Hepatitis C treatment outcome among people in prison: The SToP-C study.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) burden is higher among people in prison given high prevalence of injecting drug use. This study evaluated direct-acting antiviral (DAA) treatment outcome in prisons. METHODS: The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study enrolled individuals incarcerated in four Australian prisons (2017-2019). Participants with detectable HCV RNA were offered sofosbuvir-velpatasvir for 12 weeks. Sustained virological response (SVR) was assessed in intention-to-treat (ITT; participants commencing treatment and due for SVR assessment before study close) and per-protocol (PP; participants with documented treatment completion and SVR assessment) populations. RESULTS: Among 799 participants with HCV, 324 (41%) commenced treatment (94% male; median age, 32 years; median duration of incarceration, 9 months). In ITT population (n = 310), 201 had documented treatment completion (65% [95% CI: 59-70]), and 137 achieved SVR (ITT-SVR: 44% [95% CI: 39-50]). In PP population (n = 143), 137 achieved SVR (PP-SVR: 96% [95% CI: 91-98]). Six participants had quantifiable HCV RNA at SVR assessment from treatment failure (n = 2) or reinfection (n = 4). Release or inter-prison transfer was common reasons for no documented treatment completion (n = 106/109 [97%]) and no SVR assessment (n = 57/58 [98%]). In ITT analysis, longer incarceration was associated with increased SVR (adjusted OR per month 1.03 [95% CI: 1.01-1.04]). CONCLUSION: Among participants who completed DAA treatment and were assessed for SVR, treatment outcome was consistent with non-prison clinical studies. However, most individuals did not complete treatment or lacked study-documented treatment outcome due to release or transfer. Strategies to accommodate dynamic prisoner populations are required to ensure continuity of HCV care, including treatment completion and post-treatment care.

Health-Related Quality of Life of People Who Inject Drugs: The Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage Study.

OBJECTIVES: There is limited research on health-related quality of life (HRQoL) among people who inject drugs (PWID). We evaluated the HRQoL and associated factors among a cohort of PWID in Australia. METHODS: Participants were enrolled in an observational cohort study (the Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage Study) from May 2018 to September 2019 (wave 1) and November 2019 to June 2021 (wave 2). Participants completed the EQ-5D-5L survey at enrolment. Two-part models were used to assess the association of clinical and socioeconomic characteristics with EQ-5D-5L scores. RESULTS: Among 2395 participants (median age, 43 years; 66% male), 65% reported injecting drug use in the past month, 20% had current hepatitis C virus (HCV) infection, and 68% had no/mild liver fibrosis (F0/F1). Overall, the mean EQ-5D-5L and EQ-visual analog scale scores were 0.78 and 57, respectively. In adjusted analysis, factors associated with significantly lower EQ-5D-5L scores include older ages, female (marginal effect = -0.03, P = .014), being homeless (marginal effect = -0.04, P = .040), and polysubstance use (marginal effect = -0.05, P < .001). Factors associated with significantly higher EQ-5D-5L scores were being Aboriginal/Torres Strait Islander (marginal effect = 0.03, P = .021) and recent injecting drug use in the past 12 months. Current HCV infection and liver fibrosis stage were not associated with reduced HRQoL among the study participants. CONCLUSIONS: PWID experienced a lower HRQoL compared with the general population. Further research is needed to understand HRQoL in this population to facilitate the development of multifaceted care models for PWID beyond HCV cure and inform health economic analyses for identifying optimal health strategies for PWID.

Fructose malabsorption and fructan malabsorption are associated in patients with irritable bowel syndrome.

BACKGROUND: Food malabsorption and intolerance is implicated in gastrointestinal symptoms among patients with irritable bowel syndrome (IBS). Key triggers include fructose and fructan. Prior studies examined fructose and fructan malabsorption separately in IBS patients. None have concurrently assessed both within the same patient group. We aimed to investigate the association between fructose and fructan malabsorption in the same patients with IBS using hydrogen breath testing (HBT). METHODS: We retrospectively identified patients with IBS who underwent fructose and fructan HBTs and abstracted their results from the electronic medical record. Fructose and fructan HBTs were performed by administering a 25 g fructose solution or 10 g fructan solution, followed by breath hydrogen readings every 30 min for 3 h. Patients were positive for fructose or fructan malabsorption if breath hydrogen levels exceeded 20 ppm. RESULTS: Of 186 IBS patients, 71 (38.2%) were positive for fructose malabsorption and 91 (48.9%) were positive for fructan malabsorption. Of these patients, 42 (22.6%) were positive for fructose malabsorption and fructan malabsorption. Positive fructose HBT readings were significantly associated with positive fructan HBT readings (p = 0.0283). Patients positive for fructose malabsorption or fructan malabsorption had 1.951 times higher odds of testing positive for the other carbohydrate. CONCLUSIONS: Our results reveal a clinically significant association between fructose malabsorption and fructan malabsorption in patients with IBS. Fructan malabsorption should be assessed in patients with fructose malabsorption, and vice versa. Further studies are required to identify the mechanisms underlying our findings.

A 'one-stop-shop' point-of-care hepatitis C RNA testing intervention to enhance treatment uptake in a reception prison: The PIVOT study.

BACKGROUND & AIMS: Prisons are key venues for scaling-up hepatitis C virus (HCV) testing and treatment. Complex clinical pathways and frequent movements of people in prison remain barriers to HCV care. This study evaluated the impact of a 'one-stop-shop' point-of-care HCV RNA testing intervention on treatment uptake compared with standard of care among people recently incarcerated in Australia. METHODS: PIVOT was a prospective, non-concurrent, controlled study comparing HCV treatment uptake during 'standard of care' (n = 239; November 2019-May 2020) and a 'one-stop-shop' intervention (n = 301; June 2020-April 2021) in one reception prison in Australia. The primary endpoint was uptake of direct-acting antiviral treatment at 12 weeks from enrolment. Secondary outcomes included the time taken from enrolment to each stage in the care cascade. RESULTS: A total of 540 male participants were enrolled. Median age (29 vs. 28 years) and history of injecting drug use (48% vs. 42%) were similar between standard of care and intervention phases. Among people diagnosed with current HCV infection (n = 18/63 in the standard of care phase vs. n = 30/298 in the intervention phase), the proportion initiating direct-acting antiviral treatment within 12 weeks from enrolment in the intervention phase was higher (93% [95% CI 0.78-0.99] vs. 22% [95% CI 0.64-0.48]; p <0.001), and the median time to treatment initiation was shorter (6 days [IQR 5-7] vs. 99 days [IQR 57-127]; p <0.001) compared to standard of care. CONCLUSIONS: The 'one-stop-shop' intervention enhanced treatment uptake and reduced time to treatment initiation among people recently incarcerated in Australia, thereby overcoming key barriers to treatment scale-up in the prison sector. IMPACT AND IMPLICATIONS: This study provides important insights for policymakers regarding optimal HCV testing and treatment pathways for people newly incarcerated in prisons. The findings will improve health outcomes in people in prison with chronic HCV infection by increasing testing and treatment, thereby reducing infections, liver-related morbidity/mortality, and comorbidities. The findings will change clinical practice, clinical guidelines, and international guidance, and will inform future research and national and regional strategies, in particular regarding point-of-care testing, which is being rapidly scaled-up in various settings globally. The economic impact will likely include health budget savings resulting from reduced negative health outcomes relating to HCV, and health system efficiencies resulting from the introduction of simplified models of care. CLINICAL TRIALS REGISTRATION: This study is registered at Clinicaltrials.gov (NCT04809246).

Patient-Reported Outcomes During and After Hepatitis C Virus Direct-Acting Antiviral Treatment Among People Who Inject Drugs.

OBJECTIVES: People who inject drugs (PWID) are at a high risk of hepatitis C virus (HCV) infection. HCV cure is associated with improved patient-reported outcomes (PROs), but there are little data among PWID. This study aimed to assess the change in PROs during and after HCV direct-acting antiviral (DAA) treatment. METHODS: This analysis used data from 2 clinical trials of DAA treatment in PWID. PROs assessed included health-related quality of life, social functioning, psychological distress, housing, and employment. Generalized estimating equations and group-based trajectory modeling were used to assess changes in PROs over time. RESULTS: No significant changes in the 3-level version of EQ-5D scores, EQ visual analogue scale scores, social functioning, psychological distress, and housing were observed over the 108-week study period. There was a significant increase in the proportion of participants employed (18% [95% confidence interval (CI) 12%-23%] at baseline to 28% [95% CI 19%-36%] at the end of the study). Participants were more likely to be employed at 24 weeks and 108 weeks after commencing treatment. Having stable housing increased the odds of being employed (odds ratio 1.70; 95% CI 1.00-2.90). The group-based trajectory modeling demonstrated that most outcomes remained stable during and after DAA treatment. CONCLUSIONS: Although no significant improvement was identified in health-related quality of life after HCV DAA treatment, there was a modest but significant increase in employment during study follow-up. The study findings support the need for multifaceted models of HCV care for PWID addressing a range of issues beyond HCV treatment to improve quality of life.

Food elimination diet is a viable alternative therapy for eosinophilic esophagitis responsive to proton pump inhibitors.

BACKGROUND: First-line treatment of eosinophilic esophagitis (EoE) includes monotherapy with proton-pump inhibitors (PPIs), food elimination diet (FED), or topical corticosteroids. Current guidelines suggest patients with EoE should continue any responsive first-line monotherapies. However, the efficacy of FED monotherapy in patients with EoE responsive to PPI monotherapy has not been well studied. Our study aimed to investigate how attempting FED monotherapy after experiencing remission of EoE after PPI monotherapy influenced long-term EoE management. METHODS: We retrospectively identified patients with EoE responsive to PPI monotherapy who trialed FED monotherapy. We then employed a mixed method approach to a prospective cohort. Selected patients were observed long term for quantitative outcomes, while qualitative results were obtained from patient surveys regarding their perspectives on the trial of FED monotherapy. RESULTS: We identified 22 patients who trialed FED monotherapy after experiencing remission of EoE following PPI monotherapy. Of these 22 patients, 13 had remission of EoE with FED monotherapy, while 9 had re-activation of EoE. Out of 22 patients, 15 were enrolled in a cohort for observation. No exacerbations of EoE occurred while on maintenance treatment. Most patients stated that they would recommend this process to others with EoE (93.33%) and that trial of FED monotherapy helped them identify a treatment plan that aligned with their lifestyle (80%). CONCLUSION: Our work shows that FED monotherapy can be an effective alternative for patients with EoE responsive to PPI monotherapy that may improve patient quality of life, suggesting alternative treatment options should be considered for monotherapy-responsive EoE.

Health-related quality of life among people who inject drugs in Australia.

PURPOSE: There is limited research on health-related quality of life (HRQoL) among people who inject drugs (PWID). We aimed to evaluate factors associated with HRQoL among a cohort of PWID in Australia. METHODS: Participants were enrolled in an observational cohort study (the LiveRLife Study) between 2014 and 2018 at 15 sites in Australia. They provided fingerstick whole-blood samples for point-of-care HCV RNA testing and underwent transient elastography to assess liver disease. Participants completed the EQ-5D-3L survey at enrolment. Regression models were used to assess the impact of clinical and socioeconomic characteristics on the EQ-5D-3L scores. RESULTS: Among 751 participants (median age, 43 years; 67% male), 63% reported injection drug use in the past month, 43% had current HCV infection, and 68% had no/mild liver fibrosis (F0/F1). The mean EQ-5D-3L and EQ-VAS scores were 0.67 and 62, respectively, for the overall study population. There was no significant difference in the EQ-5D-3L scores among people with and without recent injecting drug use (mean: 0.66 vs. 0.68, median: 0.73 vs. 0.78, P = 0.405), and among people receiving and not receiving opioid agonist therapy (mean: 0.66 vs. 0.68, median: 0.73 vs. 0.76, P = 0.215). Participants who were employed were found to have the highest mean EQ-5D-3L (0.83) and EQ-VAS scores (77). The presence of current HCV infection, liver fibrosis stage, and high-risk alcohol consumption had little impact on HRQoL. CONCLUSIONS: The study findings provide important HRQoL data for economic evaluations, useful for guiding the allocation of resources for HCV elimination strategies and interventions among PWID.

Diagnostic Accuracy of Assays Using Point-of-Care Testing or Dried Blood Spot Samples for the Determination of Hepatitis C Virus RNA: A Systematic Review.

BACKGROUND: Finger-stick point-of-care and dried blood spot (DBS) hepatitis C virus (HCV) RNA testing increases testing uptake and linkage to care. This systematic review evaluated the diagnostic accuracy of point-of-care testing and DBS to detect HCV RNA. METHODS: Bibliographic databases and conference presentations were searched for eligible studies. Meta-analysis was used to pool estimates. RESULTS: Of 359 articles identified, 43 studies were eligible and included. When comparing the Xpert HCV Viral Load Fingerstick assay to venous blood samples (7 studies with 987 samples), the sensitivity and specificity for HCV RNA detection was 99% (95% confidence interval [CI], 97%-99%) and 99% (95% CI, 94%-100%) and for HCV RNA quantification was 100% (95% CI, 93%-100%) and 100% (95% CI, 94%-100%). The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing was 6% (95% CI, 3%-11%). When comparing DBS to venous blood samples (28 studies with 3988 samples) the sensitivity and specificity for HCV RNA detection was 97% (95% CI, 95%-98%) and 100% (95% CI, 98%-100%) and for HCV RNA quantification was 98% (95% CI, 96%-99%) and 100% (95% CI, 95%-100%). CONCLUSIONS: Excellent diagnostic accuracy was observed across assays for detection of HCV RNA from finger-stick and DBS samples. The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing highlights the importance of operator training and quality assurance programs.

Hepatitis C Virus Reinfection Following Direct-Acting Antiviral Treatment in the Prison Setting: The SToP-C Study.

BACKGROUND: Injection drug use (IDU) following treatment for hepatitis C virus (HCV) infection may lead to reinfection, particularly if access to harm reduction services is suboptimal. This study assessed HCV reinfection risk following direct-acting antiviral therapy within Australian prisons that had opioid agonist therapy (OAT) programs but did not have needle and syringe programs (NSPs). METHODS: The Surveillance and Treatment of Prisoners With Hepatitis C (SToP-C) study enrolled people incarcerated in 4 prisons between 2014 and 2019. Participants treated for HCV were followed every 3-6 months to identify reinfection (confirmed by sequencing). Reinfection incidence and associated factors were evaluated. RESULTS: Among 388 participants receiving treatment, 161 had available posttreatment follow-up and were included in analysis (92% male; median age, 33 years; 67% IDU in prison; median follow-up 9 months). Among those with recent (in the past month) IDU (n = 71), 90% had receptive needle/syringe sharing. During 145 person-years (PY) of follow-up, 18 cases of reinfection were identified. Reinfection incidence was 12.5/100 PY (95% confidence interval [CI]: 7.9-19.8) overall, increasing to 28.7/100 PY (95% CI: 16.3-50.6) among those with recent IDU and needle/syringe sharing. In adjusted analysis, recent IDU with needle/syringe sharing was associated with increased reinfection risk (adjusted hazard ratio [aHR], 4.74 [95% CI: 1.33-16.80]; P = .016) and longer HCV testing interval with decreased risk (ie, chance of detection; aHR, 0.41 per each month increase [95% CI: .26-.64]; P < .001). CONCLUSIONS: A high rate of HCV reinfection was observed within prison. Posttreatment surveillance and retreatment are -essential to limit the impact of reinfection. High-coverage OAT and NSPs should be considered within prisons. CLINICAL TRIALS REGISTRATION: NCT02064049.

Reinfection Following Successful Direct-acting Antiviral Therapy for Hepatitis C Virus Infection Among People Who Inject Drugs.

BACKGROUND: The aim of this analysis was to calculate the incidence of hepatitis C virus (HCV) reinfection and associated factors among 2 clinical trials of HCV direct-acting antiviral treatment in people with recent injecting drug use or currently receiving opioid agonist therapy (OAT). METHODS: Participants who achieved an end-of-treatment response in 2 clinical trials of people with recent injecting drug use or currently receiving OAT (SIMPLIFY and D3FEAT) enrolled between March 2016 and February 2017 in 8 countries were assessed for HCV reinfection, confirmed by viral sequencing. Incidence was calculated using person-time of observation and associated factors were assessed using Cox proportional hazard models. RESULTS: Seventy-three percent of the population at risk of reinfection (n = 177; median age, 48 years; 73% male) reported ongoing injecting drug use. Total follow-up time at risk was 254 person-years (median, 1.8 years; range, 0.2-2.8 years). Eight cases of reinfection were confirmed for an incidence of 3.1/100 person-years (95% confidence interval [CI], 1.6-6.3) overall and 17.9/100 person-years (95% CI, 5.8-55.6) among those who reported sharing needles/syringes. Younger age and needle/syringe sharing were associated with HCV reinfection. CONCLUSIONS: These data demonstrate the need for ongoing monitoring and improved strategies to prevent HCV reinfection following successful treatment among people with ongoing injecting drug use to achieve HCV elimination. CLINICAL TRIALS REGISTRATION: NCT02336139 and NCT02498015.

Patterns of Drug and Alcohol Use and Injection Equipment Sharing Among People With Recent Injecting Drug Use or Receiving Opioid Agonist Treatment During and Following Hepatitis C Virus Treatment With Direct-acting Antiviral Therapies: An International Study.

BACKGROUND: In many settings, recent or prior injection drug use remains a barrier to accessing direct-acting antiviral treatment (DAA) for hepatitis C virus (HCV) infection. We examined patterns of drug and alcohol use and injection equipment sharing among people with recent injecting drug use or receiving opioid agonist treatment (OAT) during and following DAA-based treatment. METHODS: SIMPLIFY and D3FEAT are phase 4 trials evaluating the efficacy of DAA among people with past 6-month injecting drug use or receiving OAT through a network of 25 international sites. Enrolled in 2016-2017, participants received sofosbuvir/velpatasvir (SIMPLIFY) or paritaprevir/ritonavir/dasabuvir/ombitasvir ± ribavirin (D3FEAT) for 12 weeks and completed behavioral questionnaires before, during, and up to 2 years posttreatment. The impact of time in HCV treatment and follow-up on longitudinally measured longitudinally measured behaviors was estimated using generalized estimating equations. RESULTS: At screening, of 190 participants (mean age, 47 years; 74% male), 62% reported any past-month injecting 16% past-month injection equipment sharing, and 61% current OAT. Median alcohol use was 2 (Alcohol Use Disorders Identification Test-Consumption; range, 1-12). During follow-up, opioid injecting (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.92-0.99) and sharing (OR, 0.87; 95% CI, 0.80-0.94) decreased, whereas no significant changes were observed for stimulant injecting (OR, 0.98; 95% CI, 0.94-1.02) or alcohol use (OR, 0.99; 95% CI, 0.95-1.04). CONCLUSIONS: Injecting drug use and risk behaviors remained stable or decreased following DAA-based HCV treatment. Findings further support expanding HCV treatment to all, irrespective of injection drug use. CLINICAL TRIALS REGISTRATION: SIMPLIFY, NCT02336139; D3FEAT, NCT02498015.

Adherence to Once-daily and Twice-daily Direct-acting Antiviral Therapy for Hepatitis C Infection Among People With Recent Injection Drug Use or Current Opioid Agonist Therapy.

BACKGROUND: This study investigated adherence and associated factors among people with recent injection drug use (IDU) or current opioid agonist therapy (OAT) and compared once-daily to twice-daily hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy. METHODS: SIMPLIFY and D3FEAT are international, multicenter studies that recruited participants with recent IDU (previous 6 months; SIMPLIFY, D3FEAT) or current OAT (D3FEAT) between March 2016 and February 2017 in 8 countries. Participants received sofosbuvir/velpatasvir (once daily; SIMPLIFY) or paritaprevir/ritonavir/ombitasvir, dasabuvir (twice daily) ± ribavirin (D3FEAT) for 12 weeks administered in electronic blister packs. We evaluated overall adherence (proportion of prescribed doses taken) and nonadherence (<90% adherent) between dosing patterns. RESULTS: Of 190 participants, 184 (97%) completed treatment. Median adherence was 92%, with higher adherence among those receiving once-daily vs twice-daily therapy (94% vs 87%, P = .005). Overall, 40% of participants (n = 76) were nonadherent (<90% adherent). Recent stimulant injecting (odds ratio [OR], 2.48 [95% confidence interval {CI}, 1.28-4.82]), unstable housing (OR, 2.18 [95% CI, 1.01-4.70]), and twice-daily dosing (OR, 2.81 [95% CI, 1.47-5.36]) were associated with nonadherence. Adherence decreased during therapy. Sustained virologic response was high in nonadherent (89%) and adherent populations (95%, P = .174), with no difference in SVR between those who did and did not miss 7 consecutive doses (92% vs 93%, P = .897). CONCLUSIONS: This study demonstrated high adherence to once- and twice-daily DAA therapy among people with recent IDU or currently receiving OAT. Nonadherence described did not impact treatment outcomes, suggesting forgiveness to nonadherence.

Hepatitis C reinfection after successful antiviral treatment among people who inject drugs: A meta-analysis.

BACKGROUND & AIMS: HCV reinfection following successful treatment can compromise treatment outcomes. This systematic review assessed the rate of HCV reinfection following treatment among people with recent drug use and those receiving opioid agonist therapy (OAT). METHODS: We searched bibliographic databases and conference abstracts for studies assessing post-treatment HCV reinfection rates among people with recent drug use (injecting or non-injecting) or those receiving OAT. Meta-analysis was used to cumulate reinfection rates and meta-regression was used to explore heterogeneity across studies. RESULTS: Thirty-six studies were included (6,311 person-years of follow-up). The overall rate of HCV reinfection was 5.9/100 person-years (95% CI 4.1-8.5) among people with recent drug use (injecting or non-injecting), 6.2/100 person-years (95% CI 4.3-9.0) among people recently injecting drugs, and 3.8/100 person-years (95% CI 2.5-5.8) among those receiving OAT. Reinfection rates were comparable following interferon-based (5.4/100 person-years; 95% CI 3.1-9.5) and direct-acting antiviral (3.9/100 person-years; 95% CI 2.5-5.9) therapy. In stratified analysis, reinfection rates were 1.4/100 person-years (95% CI 0.8-2.6) among people receiving OAT with no recent drug use, 5.9/100 person-years (95% CI 4.0-8.6) among people receiving OAT with recent drug use, and 6.6/100 person-years (95% CI 3.4-12.7) among people with recent drug use not receiving OAT. In meta-regression analysis, longer follow-up was associated with lower reinfection rate (adjusted rate ratio [aRR] per year increase in mean/median follow-up 0.77; 95% CI 0.69-0.86). Compared with people receiving OAT with no recent drug use, those with recent drug use receiving OAT (aRR 3.50; 95% CI 1.62-7.53), and those with recent drug use not receiving OAT (aRR 3.96; 95% CI 1.82-8.59) had higher reinfection rates. CONCLUSION: HCV reinfection risk following treatment was higher among people with recent drug use and lower among those receiving OAT. The lower rates of reinfection observed in studies with longer follow-up suggested higher reinfection risk early post-treatment. LAY SUMMARY: Our findings demonstrate that although reinfection by hepatitis C virus occurs following successful treatment in people with recent drug use, the rate of hepatitis C reinfection is lower than the rates of primary infection reported in the literature for this population - reinfection should not be used as a reason to withhold therapy from people with ongoing injecting drug use. The rate of hepatitis C reinfection was lowest among people receiving opioid agonist therapy with no recent drug use. These data illustrate that harm reduction services are required to reduce the reinfection risk, while regular post-treatment hepatitis C assessment is required for early detection and retreatment.

A Global Meta-analysis of the Prevalence of HIV, Hepatitis C Virus, and Hepatitis B Virus Among People Who Inject Drugs-Do Gender-Based Differences Vary by Country-Level Indicators?

BACKGROUND: Women-specific factors exist that increases vulnerability to drug-related harms from injection drug use, including blood-borne viruses (BBVs), but gender-based differences in BBV prevalence have not been systematically examined. METHODS: We conducted meta-analyses to estimate country, regional, and global prevalence of serologically confirmed human immunodeficiency virus (HIV), hepatitis C virus (HCV; based on detection of anti-HCV antibody), and hepatitis B virus (HBV; based on detection of HBV surface antigen) in people who inject drugs (PWID), by gender. Gender-based differences in the BBV prevalence (calculated as the risk among women relative to the risk among men) were regressed on country-level prevalence and inequality measures (Gender inequality index, Human development index, Gini coefficient, and high, low or middle income of the country). RESULTS: Gender-based differences varied by countries and regions. HIV prevalence was higher among women than men in sub-Saharan Africa (relative risk [RR], 2.8; 95% confidence interval [CI], 1.8-4.4) and South Asia (RR, 1.7; 95% CI, 1.1-2.7); anti-HCV was lower among women in the Middle East and North Africa (RR, 0.6; 95% CI, .5-.7) and East and Southeast Asia (RR, 0.8; 95% CI, .7-.9). Gender-based differences varied with country-levels of the BBV prevalence in the general population, human development, and income distribution. CONCLUSION: HIV was more prevalent in women who inject drugs as compared to their male counterparts in some countries, but there is variation between and within regions. In countries where women are at higher risks, there is a need to develop gender-sensitive harm-reduction services for the particularly marginalized population of women who inject drugs.

Treatment adherence and support for people who inject drugs taking direct-acting antiviral therapy for hepatitis C infection.

A community-based public health facility in Sydney, Australia, the Kirketon Road Centre (KRC), provides health care to people who inject drugs (PWID), homeless and other marginalized people. Since March 2016, KRC has provided treatment for chronic hepatitis C virus (HCV) with direct-acting antivirals (DAAs). We aimed to evaluate treatment adherence amongst clients taking DAAs in a highly marginalized population. All clients who commenced DAA therapy prior to March 2018 at KRC were included in this observational cohort with a subset of clients attending daily or weekly for enhanced adherence support and dosing. Demographic, behavioural, clinical measures and medication dosing were recorded, and adherence was calculated as the proportion of doses taken during the expected treatment duration. Factors associated with adherence were examined using logistic regression. A total of 242 individuals commenced DAA therapy, of whom 79 (32%) received enhanced adherence support. Enhanced support was associated with homelessness, daily injecting, Aboriginality, mental health co-morbidity and poly-drug use (all P < .001). Overall adherence was 86%, and 92% of patients missed one or more doses (median 10, IQR 4-24). At least 90% adherence during planned duration was seen in 38%, but increased to 66% by continuing therapy beyond planned duration. Intention-to-treat SVR12 was 68% and 66% in the enhanced adherence support sub-population, with 29% lost to follow-up by SVR12 testing. There were only 2 (0.8%) documented virological failures. Per-protocol SVR12 was 99% and 96% in the enhanced adherence support sub-population. In conclusion, adherence support may benefit those with multiple markers of marginalization. Extension of therapy beyond planned duration is a pragmatic strategy to enhance completion. Strategies to improve follow-up, particularly post-treatment are required.

Australia on track to achieve WHO HCV elimination targets following rapid initial DAA treatment uptake: A modelling study.

Subsidized direct-acting antiviral (DAA) treatment recently became available to all adults living with chronic hepatitis C virus (HCV) in Australia. Based on rapid uptake (32 600 people initiated DAA in 2016), we estimated the impact on HCV epidemiology and mortality in Australia and determined if Australia can meet the WHO HCV elimination targets by 2030. Using a mathematical model, we simulated pessimistic, intermediate and optimistic DAA treatment scenarios in Australia over 2016-2030. We assumed treatment and testing rates were initially higher for advanced fibrosis and the same across HCV transmission risk level sub-populations. We also assumed constant testing rates after 2016. We compared the results to the 2015 level and a counterfactual (IFN-based) scenario. During 2016-2030, we estimated an intermediate DAA treatment scenario (2016, 32 600 treated; 2017, 21 370 treated; 2018 17 100 treated; 2019 and beyond, 13 680 treated each year) would avert 40 420 new HCV infections, 13 260 liver-related deaths (15 320 in viraemic; -2060 in cured) and 10 730 HCC cases, equating to a 53%, 63% and 75% reduction, respectively, compared to the IFN-based scenario. The model also estimated that Australia will meet the WHO targets of incidence and treatment by 2028. Time to a 65% reduction in liver-related mortality varied considerably between HCV viraemic only cases (2026) and all cases (2047). Based on a feasible DAA treatment scenario incorporating declining uptake, Australia should meet key WHO HCV elimination targets in 10 to15 years. The pre-DAA escalation in those with advanced liver disease makes the achievement of the liver-related mortality target difficult.

Adherence to response-guided pegylated interferon and ribavirin for people who inject drugs with hepatitis C virus genotype 2/3 infection: the ACTIVATE study.

BACKGROUND: The aims of this analysis were to investigate treatment completion and adherence among people with ongoing injecting drug use or receiving opioid substitution therapy (OST) in a study of response-guided therapy for chronic HCV genotypes 2/3 infection. METHODS: ACTIVATE was a multicenter clinical trial recruited between 2012 and 2014. Participants with genotypes 2/3 were treated with directly observed peg-interferon alfa-2b (PEG-IFN) and self-administered ribavirin for 12 (undetectable HCV RNA at week 4) or 24 weeks (detectable HCV RNA at week 4). Outcomes included treatment completion, PEG-IFN adherence, ribavirin adherence, and sustained virological response (SVR, undetectable HCV RNA >12 weeks post-treatment). RESULTS: Among 93 people treated, 59% had recently injected drugs (past month), 77% were receiving OST and 56% injected drugs during therapy. Overall, 76% completed treatment. Mean on-treatment adherence to PEG-IFN and ribavirin were 98.2% and 94.6%. Overall, 6% of participants missed >1 dose of PEG-IFN and 31% took <95% of their prescribed ribavirin., Higher treatment completion was observed among those receiving 12 vs. 24 weeks of treatment (97% vs. 46%, P < 0.001) while the proportion of participants with 95% on-treatment ribavirin adherence was similar between groups (67% vs. 72%, P = 0.664). Receiving 12 weeks of therapy was independently associated with treatment completion. No factors were associated with 95% RBV adherence. Neither recent injecting drug use at baseline nor during therapy was associated with treatment completion or adherence to ribavirin. In adjusted analysis, treatment completion was associated with SVR (aOR 23.9, 95% CI 2.9-193.8). CONCLUSIONS: This study demonstrated a high adherence to directly observed PEG-IFN and self-administered ribavirin among people with ongoing injecting drug use or receiving OST. These data also suggest that shortening therapy from 24 to 12 weeks can lead to improved treatment completion. Treatment completion was associated with improved response to therapy. ACTIVATE trial registration number: NCT01364090 - May 31, 2011.

Interventions to reduce harms related to drug use among people who experience incarceration: systematic review and meta-analysis.

BACKGROUND: Mortality, suicide, self-harm, and substance use are elevated among people who are incarcerated. There is a wide range of heterogeneous interventions aimed at reducing these harms in this population. Previous reviews have focused on specific interventions or limited their findings to drug use and recidivism and have not explored interventions delivered after release from prison. Our aim is to examine the effect of interventions delivered to people who use drugs during incarceration or after release from incarceration, on a wide range of outcomes. METHODS: In this systematic review and meta-analysis, we searched Embase, MEDLINE, and PsycINFO databases up until Sept 12, 2023 for studies published from Jan 1, 1980 onwards. All studies evaluating the effectiveness of any intervention on drug use, recidivism outcomes, sexual or injecting risk behaviours, or mortality among people who use psychoactive drugs and who were currently or recently incarcerated were included. Studies without a comparator or measuring only alcohol use were excluded. Data extracted from each study included demographic characteristics, interventions, and comparisons. Pooled odds ratios and risk ratios were calculated using random-effects meta-analyses. FINDINGS: We identified 126 eligible studies (47 randomised controlled trials and 79 observational studies) encompassing 18 interventions; receiving opioid-agonist treatment (OAT) in prison reduced the risk of death in prison (one study; hazard ratio 0·25; 95% CI 0·13-0·48), whereas receiving OAT in the first 4 weeks following release reduced risk of death in the community (two studies; relative risk 0·24; 95% CI 0·15-0·37). Therapeutic community interventions reduced re-arrest at 6-12 months (six studies; odds ratio [OR] 0·72; 95% CI 0·55-0·95) and reincarceration at 24 months (two studies; OR 0·66; 95% CI 0·48-0·96). There was scarce evidence that OAT and syringe service provision are effective in reducing injecting risk behaviours and needle and syringe sharing. INTERPRETATION: There are effective interventions to reduce mortality and recidivism for people who use drugs who have been incarcerated. Nonetheless, there are also substantial gaps in the research examining the effect of interventions on risk behaviours and mortality during incarceration and a need for randomised designs examining outcomes for people who use drugs after release. FUNDING: Australian National Health and Medical Research Council.