Treating people where they are: Nurse-led micro-elimination of hepatitis C in supported housing sites for networks of people who inject drugs in Victoria, Canada.

To achieve the World Health Organization's goal of eliminating hepatitis C (HCV) by 2030 requires enhanced HCV testing and treatment among people who use drugs (PWUD). Micro-elimination of HCV is a strategy to target HCV testing and treatment efforts to specific segments of the population. From February to December 2018 nurses initiated a "seek & treat" micro-elimination approach, increasing outreach and removing barriers to accessing HCV treatment in a clinic setting by testing and treating individuals, including PWUD, where they live. The aim of this study was to evaluate the proportion of clients with HCV antibodies and HCV RNA and the response to direct acting agent (DAA therapy) among people who live at or have social connections to local supportive housing sites through this nurse-led micro-elimination project in Victoria, Canada. A chart review of electronic medical records and case management documentation was used to collect relevant data of participants treated with DAA therapy, identified through specific housing site testing and outreach interventions. In total, 180 people were tested for HCV antibodies, 72 (40%) were antibody positive: 51 (28%) were RNA positive, 13 (7%) had spontaneously cleared and 8 (4%) had been previously treated. Of the 51 that were currently living with HCV, 43 people were started on treatment, 39 have achieved sustained virologic response (SVR). By providing treatment to clients in their homes and with their friends, clinicians have been able to treat clients, including those with limited contact with the health care system.

Exploring nurse-led HIV Pre-Exposure Prophylaxis in a community health care clinic.

OBJECTIVES: Gay, bisexual, and other men who have sex with men (gbMSM) are 131 times more likely to acquire HIV compared with other Canadian men. Pre-Exposure Prophylaxis (PrEP) for HIV has the potential to reduce or eliminate disparities in HIV acquisition among key affected populations. This paper aims to discuss the feasibility and utility of a nurse-led PrEP program administered by the Cool Aid Community Health Centre (CACHC) in Victoria, British Columbia as a public health PrEP program was initiated. DESIGN, SAMPLE AND MEASUREMENTS: A retrospective chart review of 124 gbMSM patients accessing PrEP at CACHC in 2018 collected information on patient demographics, STI testing results, and PrEP prescription pick-ups at 3 time points. RESULTS: Ninety-nine (79.8%) patients have continued on PrEP, as defined as having picked up their second 90-day PrEP prescription. Both older age and having an Sexually Transmitted Infection after PrEP enrolment were significantly associated with staying on PrEP; decreased risk perceptions contributed most to clinic-level discontinuance. Very few patients who stayed on PrEP have transitioned to their own General Practitioner. CONCLUSIONS: Patients appear to recognize their risk and are continuing on PrEP to reduce their risk of HIV. As evidenced by ability to recruit and maintain patients, we conclude that nurse-led PrEP at community health centres supports access and uptake of essential health services to optimize individual and population health.

'I just never wanted them to feel uncomfortable': Barriers to pharmacy-based identification and treatment of hepatitis C in Victoria, Canada.

Background: Canada is currently on target to reach the 2030 WHO goal of HCV elimination. Continued high rates of treatment are required to meet this goal. Novel models such as Tayside, Scotland pharmacy-based HCV screening and treatment have proven successful to engage people who use drugs (PWUD) in HCV therapy with a simplified, task-shifted cascade of care. This study seeks to determine whether these successes can be replicated at community pharmacies in Victoria BC. Methods: Four pharmacies who work with PWUD and provide opioid agonist therapy were trained to provide consent and perform point-of-care HCV antibody screening. They were supported by study nurse to link to HCV RNA testing when antibody positive patients were identified, with HCV treatment offered to RNA positive participants. Qualitative interviews were conducted with five pharmacy staff to explore experiences and feasibility of pharmacists in HCV care cascade. Results: Pharmacy staff completed 200 HCV OraQuick tests between October 2020 and June 2022: 65 HCV antibody positive, 29 HCV RNA negative (25 previously treated and 4 self-cleared). Of the 26 RNA positive participants, one is awaiting treatment, 25 people have started treatment, 22 achieving SVR. Although the onset of the COVID-19 pandemic was a fundamental barrier incorporating HCV testing at pharmacies, stigma related to HCV and illicit drug use continues to impact this process. Conclusions: This innovative pharmacy-based approach found people with limited connection to primary health care to test and treat HCV but requires more training and support to be more widely feasible.

Resveratrol induces cellular senescence with attenuated mono-ubiquitination of histone H2B in glioma cells.

Resveratrol (3,4',5-trihydroxy-trans-stilbene), a polyphenol naturally occurring in grapes and other plants, has cancer chemo-preventive effects and therapeutic potential. Although resveratrol modulates multiple pathways in tumor cells, how resveratrol or its affected pathways converge on chromatin to mediate its effects is not known. Using glioma cells as a model, we showed here that resveratrol inhibited cell proliferation and induced cellular hypertrophy by transforming spindle-shaped cells to enlarged, irregular and flatten-shaped ones. We further showed that resveratrol-induced hypertrophic cells expressed senescence-associated-ß-galactosidase, suggesting that resveratrol-induced cellular senescence in glioma cells. Consistent with these observations, we demonstrated that resveratrol inhibited clonogenic efficiencies in vitro and tumor growth in a xenograft model. Furthermore, we found that acute treatment of resveratrol inhibited mono-ubiquitination of histone H2B at K120 (uH2B) in breast, prostate, pancreatic, lung, brain tumor cells as well as primary human cells. Chronic treatment with low doses of resveratrol also inhibited uH2B in the resveratrol-induced senescent glioma cells. Moreover, we showed that depletion of RNF20, a ubiquitin ligase of histone H2B, inhibited uH2B and induced cellular senescence in glioma cells in vitro, thereby recapitulated the effects of resveratrol. Taken together, our results suggest that uH2B is a novel direct or indirect chromatin target of resveratrol and RNF20 plays an important role in inhibiting cellular senescence programs that are intact in glioma cells.

Reinfection following successful direct-acting antiviral therapy for HCV infection among people attending an inner-city community health centre in Victoria, Canada.

BACKGROUND: Studies of HCV reinfection following direct-acting antiviral (DAA) therapy among PWID have been limited by short follow-up and small case numbers. This study evaluated the incidence of HCV reinfection following successful DAA therapy among people attending an inner-city community health centre in Victoria, Canada. METHODS: In this observational study, participants treated with DAA therapy between November 2014 and December 31, 2019 were included. Retrospective chart review was performed to assess demographics, recent injecting drug use at treatment initiation (previous six months), opioid agonist treatment (OAT), and HIV. Endpoints included sustained virologic response (SVR), HCV reinfection, and mortality. RESULTS: Of 482 participants initiating DAA treatment, 30% were female, 46% were receiving OAT, 49% had recent injection drug use, 15% had HIV/HCV coinfection, and 22% had cirrhosis. Treatment completion was 97% (468/482; 12 discontinued therapy, and 2 died during treatment). SVR was 87% (418/482). Outcomes among those who completed treatment but did not achieve SVR (n=53), included loss to follow-up (n=11), HCV RNA for SVR testing not completed (n=18), viral relapse (n=6), reinfection (n=5) and viral recurrence (n=5, unable to distinguish viral relapse from reinfection), and death (n=7). The rate of HCV reinfection was 3.6/100 person-years (95% confidence interval [CI] 2.4-5.5; 22 cases; 602 person-years follow-up). Factors associated with an increased risk of HCV reinfection included recent injection drug use (adjusted relative risk [aRR] 8.55, 95% CI 1.98-36.96) and HIV co-infection (aRR 2.35, 95% CI 1.01-5.44). Fifty-five people died (overdose, n=19) during (n=2) or following (n=53) therapy (7.4/100 person-years; 95% CI 5.6-9.6). CONCLUSION: This study demonstrates ongoing reinfection among a marginalized population at an inner-city community health centre, with higher rates among those with HIV and recent injecting drug use. The rates of reinfection and mortality highlight the importance of integrating HCV care with strategies to address drug-related harms.

Direct-acting antiviral treatment for hepatitis C, reinfection and mortality among people attending an inner-city community health centre in Victoria, Canada.

BACKGROUND: Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) has been shown to be effective among PWID, but more real-world data on treatment outcomes is needed. The aim of this analysis was to assess the efficacy of DAA therapy, and the rate of reinfection and mortality among people attending an inner-city community health centre in Victoria, Canada. METHODS: In this retrospective study, patients treated with DAA therapy between November 2014 and Dec 31, 2017 were included. Retrospective chart review was performed to assess recent injecting drug use (IDU, previous six months) or receipt of opioid agonist treatment (OAT). The primary endpoint was Sustained Virologic Response (SVR12). Secondary endpoints included HCV reinfection and mortality. RESULTS: Of 270 patients who initiated DAA treatment (31% female), 20% (n=54) had HIV/HCV coinfection, 32% (n=84) had cirrhosis, 67% (n=181) had genotype 1, 6% (n=15) had genotype 2, 26% (n=69) had genotype 3. 46% (n=125) of patients were receiving OAT and 49% (n=132) reported recent IDU. 98% (n=265) completed treatment; two people stopped due to mental health, two people died, and one was non-adherent. 92% (249 of 270) achieved SVR12. 16 patients with End of Treatment (EOT) response did not have a SVR12; 7 were lost to follow-up; 2 people refused bloodwork; 2 people died; 1 had reinfection; and 4 had viral relapse. There was no difference in SVR12 by OAT (OAT, 93% vs. no OAT, 91%, P=0.435), recent injecting drug use (yes, 92% vs. no, 92%, P=0.904), or HIV status (HIV, 92% vs. no HIV, 94%, P=0.498). Eight cases of HCV reinfection were observed over 253 person-years of follow up (3.2 cases per 100 person-years; 95% CI 1.6-6.3). Twenty people died (6.3 per 100 person-years; 95% CI 3.9-10.3), including two during therapy (drug overdose, n=2) and 18 following therapy completion (drug overdose, n=7). CONCLUSION: This study demonstrates that DAA treatment is effective among a marginalized population receiving care in an inner-city community health centre. The high mortality in this study highlights the importance of integrating HCV care within a framework addressing drug-related harms, preventing overdose mortality, addressing social inequalities, and improving the health of PWID.