Impact of screening and doxycycline prevention on the syphilis epidemic among men who have sex with men in British Columbia: a mathematical modelling study.

Background: Men who have sex with men (MSM) in British Columbia (BC) are disproportionately affected by infectious syphilis and HIV. In this study, we developed a co-interaction model and evaluated the impact and effectiveness of possible interventions among different MSM subgroups on the syphilis epidemic. Methods: We designed a deterministic compartmental model, which stratified MSM by HIV status and HIV pre-exposure prophylaxis (HIV-PrEP) usage into (1) HIV-negative/unaware MSM (HIV-PrEP not recommended, not on HIV-PrEP), (2) HIV-negative/unaware MSM with HIV-PrEP recommended (not on HIV-PrEP), (3) HIV-negative/unaware MSM actively on HIV-PrEP, and (4) MSM diagnosed with HIV. We estimated the effect of scaling up syphilis testing frequency from Status Quo to six-, four-, and three-months, increasing the percentage of MSM using doxycycline prevention (Doxy-P) to 25%, 50%, and 100% of the target level, and a combination of both among subgroups (2)-(4). We also assessed the impact of these interventions on the syphilis incidence rates from 2020 to 2034 in comparison to the Status Quo scenario where no intervention was introduced. Findings: Under the Status Quo scenario, with the expansion of the HIV-PrEP program to improve syphilis testing, the syphilis incidence rate was estimated to peak at 16.1 [Credible Interval (CI):14.2-17.9] per 1,000 person-years (PYs) in 2023 and decrease to 6.7 (CI:3.8-10.9) per 1,000 PYs by 2034. The syphilis incidence rate in 2034 was estimated at 0.7 (0.3-1.3) per 1,000 PYs if MSM diagnosed with HIV could be tested every four months, and at 1.5 (0.7-3.0) per 1,000 PYs if HIV-negative/unaware MSM actively on HIV-PrEP could be tested every three months. By achieving 100% of the target coverage of Doxy-P, the syphilis incidence rate was estimated at 1.4 (0.5-3.4) if focusing on MSM diagnosed with HIV, and 2.6 (1.2-5.1) per 1,000 PYs if focusing on HIV-negative/unaware MSM actively on HIV-PrEP. Under the combined interventions, the syphilis incidence rate could be as low as 0.0 (0.0-0.1) and 0.8 (0.3-1.8) per 1,000 PYs, respectively. Interpretation: The HIV-PrEP program in BC plays a crucial role in increasing syphilis testing frequency among high-risk MSM and reducing syphilis transmission among this group. In addition, introducing Doxy-P can be an effective complementary strategy to minimize syphilis incidence, especially among MSM diagnosed with HIV. Funding: This work was funded by the Canadian Institutes of Health Research.

"To do so in a patient-centred way is not particularly lucrative": The effects of neoliberal health care on PrEP implementation and delivery.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is a highly effective biomedical intervention used by HIV-negative people to prevent HIV acquisition. Despite increased use of PrEP worldwide, several barriers to PrEP implementation have resulted in insufficient uptake, inadequate adherence, and frequent discontinuation. Our objective was to interrogate the social, political, and economic conditions shaping PrEP implementation and delivery among gay, bisexual, queer and other men who have sex with men (GBQM) in Ontario, Canada. METHODS: Six focus groups and three interviews with 20 stakeholders in Ontario (e.g., healthcare professionals, clinicians, community-based organization staff, and government staff) were conducted between July and October 2021. Participants were asked about the personal, workplace, and structural factors shaping PrEP delivery strategies for GBQM. Transcripts were analyzed using reflexive thematic analysis informed by the political economy of PrEP and employed a critique of neoliberalism. RESULTS: Participants critiqued the problematic arrangements of the current healthcare system in Canada. Neoliberal governmentality and policies have resulted in inequitable PrEP care by establishing funding structures prioritizing profit and requiring patients and providers to function as individual entrepreneurs. Consequently, healthcare disparities are compounded for marginalized peoples who lack the resources and capacity to navigate existing healthcare systems. Participants identified several pathways to improve the implementation of PrEP, including greater institutional and governmental supports for PrEP and healthcare, leveraging communities and collaboration, and moving beyond risk-based health frameworks. CONCLUSION: Socio-political-economic changes reflecting post-neoliberal principles are needed to overcome existing barriers to PrEP care, and sexual and reproductive healthcare more broadly.

Fish oil supplement use modifies the relationship between dietary oily fish intake and plasma n-3 PUFA levels: an analysis of the UK Biobank.

Observational evidence linking dietary n-3 PUFA intake and health outcomes is limited by a lack of robust validation of dietary intake using blood n-3 PUFA levels and potential confounding by fish oil supplement (FOS) use. We investigated the relationship between oily fish intake, FOS use and plasma n-3 PUFA levels in 121 650 UK Biobank (UKBB) participants. Ordinal logistic regression models, adjusted for clinical and lifestyle factors, were used to quantify the contribution of dietary oily fish intake and FOS use to plasma n-3 PUFA levels (measured by NMR spectroscopy). Oily fish intake and FOS use were reported by 38 % and 31 % of participants, respectively. Increasing oily fish intake was associated with a higher likelihood of FOS use (P < 0·001). Oily fish intake ≥ twice a week was the strongest predictor of high total n-3 PUFA (OR 6·7 (95 % CI 6·3, 7·1)) and DHA levels (6·6 (6·3, 7·1). FOS use was an independent predictor of high plasma n-3 PUFA levels (2·0 (2·0, 2·1)) with a similar OR to that associated with eating oily fish < once a week (1·9 (1·8, 2·0)). FOS use was associated with plasma n-3 PUFA levels that were similar to individuals in the next highest oily fish intake category. In conclusion, FOS use is more common in frequent fish consumers and modifies the relationship between oily fish intake and plasma n-3 PUFA levels in UKBB participants. If unaccounted for, FOS use may confound the relationship between dietary n-3 PUFA intake, blood levels of n-3 PUFAs and health outcomes.

The effect of aspirin and eicosapentaenoic acid on urinary biomarkers of prostaglandin E2 synthesis and platelet activation in participants of the seAFOod polyp prevention trial.

Urinary prostaglandin (PG) E metabolite (PGE-M) and 11-dehydro (d)-thromboxane (TX) B2 are biomarkers of cyclooxygenase-dependent prostanoid synthesis. We investigated (1) the effect of aspirin 300 mg daily and eicosapentaenoic acid (EPA) 2000 mg daily, alone and in combination, on urinary biomarker levels and, (2) whether urinary biomarker levels predicted colorectal polyp risk, during participation in the seAFOod polyp prevention trial. Urinary PGE-M and 11-d-TXB2 were measured by liquid chromatography-tandem mass spectrometry. The relationship between urinary biomarker levels and colorectal polyp outcomes was investigated using negative binomial (polyp number) and logistic (% with one or more polyps) regression models. Despite wide temporal variability in PGE-M and 11-d-TXB2 levels within individuals, both aspirin and, to a lesser extent, EPA decreased levels of both biomarkers (74% [P ≤ .001] and 8% [P ≤ .05] reduction in median 11-d-TXB2 values, respectively). In the placebo group, a high (quartile [Q] 2-4) baseline 11-d-TXB2 level predicted increased polyp number (incidence rate ratio [IRR] [95% CI] 2.26 [1.11,4.58]) and risk (odds ratio [95% CI] 3.56 [1.09,11.63]). A low (Q1) on-treatment 11-d-TXB2 level predicted reduced colorectal polyp number compared to placebo (IRR 0.34 [0.12,0.93] for combination aspirin and EPA treatment) compared to high on-treatment 11-d-TXB2 values (0.61 [0.34,1.11]). Aspirin and EPA both inhibit PGE-M and 11-d-TXB2 synthesis in keeping with shared in vivo cyclooxygenase inhibition. Colorectal polyp risk and treatment response prediction by 11-d-TXB2 is consistent with a role for platelet activation during early colorectal carcinogenesis. The use of urinary 11-d-TXB2 measurement for a precision approach to colorectal cancer risk prediction and chemoprevention requires prospective evaluation.

Attitudes of Gay, Bisexual, and Other Men Who Have Sex with Men (GBM) toward Their Use of Amphetamine-Type Stimulants and Relation to Reducing Use in Three Canadian Cities.

BACKGROUND: We explored attitudes of gay, bisexual, and other men who have sex with men (GBM) toward their amphetamine-use and associations with reduced use over time. METHODS: We recruited sexually-active GBM aged 16+ years in Montreal, Toronto, and Vancouver, Canada, from 02-2017 to 08-2019, with follow-up visits every 6-12 months until November 2020. Among participants who reported past-six-month (P6M) amphetamine-use at enrollment, we used logistic regression to identify demographic, psychological, social, mental health, other substance-use, and behavioral factors associated with reporting needing help reducing their substance-use. We used mixed-effects logistic regression to model reduced P6M amphetamine-use with perceived problematic-use as our primary explanatory variable. RESULTS: We enrolled 2,449 GBM across sites. 15.5-24.7% reported P6M amphetamine-use at enrollment and 82.6 - 85.7% reported needing no help or only a little help in reducing their substance use. Reporting needing a lot/of help or completely needing help in reducing substance-use was associated with group sex participation (AOR = 2.35, 95%CI:1.25-4.44), greater anxiety symptomatology (AOR = 2.11, 95%CI:1.16-3.83), greater financial strain (AOR = 1.35, 95%CI:1.21-1.50), and greater Escape Motive scores (AOR = 1.07, 95%CI:1.03-1.10). Reductions in P6M amphetamine-use were less likely among GBM who perceived their amphetamine-use as problematic (AOR = 0.17 95% CI 0.10 - 0.29). CONCLUSIONS: Most amphetamine-using GBM did not feel they needed help reducing their substance use, and many reported reduced amphetamine-use at subsequent visits. Those who perceived their use as problematic were less likely to reduce their use. Further interventions to assist GBM in reducing their use are needed to assist those who perceive their use as problematic.

Can we achieve better trial recruitment by presenting patient information through multimedia? Meta-analysis of 'studies within a trial' (SWATs).

BACKGROUND: People need high-quality information to make decisions about research participation. Providing information in written format alone is conventional but may not be the most effective and acceptable approach. We developed a structure for the presentation of information using multimedia which included generic and trial-specific content. Our aim was to embed 'Studies Within A Trial' (SWATs) across multiple ongoing trials to test whether multimedia presentation of patient information led to better rates of recruitment. METHODS: Five trials included a SWAT and randomised their participants to receive a multimedia presentation alongside standard information, or standard written information alone. We collected data on trial recruitment, acceptance and retention and analysed the pooled results using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised following an invitation to take part. RESULTS: Five SWATs provided data on the primary outcome of proportion of participants randomised. Multimedia alongside written information results in little or no difference in recruitment rates (pooled odds ratio = 0.96, 95% CI: 0.79 to 1.17, p-value = 0.671, I2 = 0%). There was no effect on any other outcomes. CONCLUSIONS: Multimedia alongside written information did not improve trial recruitment rates. TRIAL REGISTRATION: ISRCTN71952900, ISRCTN 06710391, ISRCTN 17160087, ISRCTN05926847, ISRCTN62869767.

Randomised, placebo-controlled, phase 3 trial of the effect of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on colorectal cancer recurrence and survival after surgery for resectable liver metastases: EPA for Metastasis Trial 2 (EMT2) study protocol.

INTRODUCTION: There remains an unmet need for safe and cost-effective adjunctive treatment of advanced colorectal cancer (CRC). The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and has anti-inflammatory as well as antineoplastic properties. A phase 2 randomised trial of preoperative EPA free fatty acid 2 g daily in patients undergoing surgery for CRC liver metastasis showed no difference in the primary endpoint (histological tumour proliferation index) compared with placebo. However, the trial demonstrated possible benefit for the prespecified exploratory endpoint of postoperative disease-free survival. Therefore, we tested the hypothesis that EPA treatment, started before liver resection surgery (and continued postoperatively), improves CRC outcomes in patients with CRC liver metastasis. METHODS AND ANALYSIS: The EPA for Metastasis Trial 2 trial is a randomised, double-blind, placebo-controlled, phase 3 trial of 4 g EPA ethyl ester (icosapent ethyl (IPE; Vascepa)) daily in patients undergoing liver resection surgery for CRC liver metastasis with curative intent. Trial treatment continues for a minimum of 2 years and maximum of 4 years, with 6 monthly assessments, including quality of life outcomes, as well as annual clinical record review after the trial intervention. The primary endpoint is CRC progression-free survival. Key secondary endpoints are overall survival, as well as the safety and tolerability of IPE. A minimum 388 participants are estimated to provide 247 CRC progression events during minimum 2-year follow-up, allowing detection of an HR of 0.7 in favour of IPE, with a power of 80% at the 5% (two sided) level of significance, assuming drop-out of 15%. ETHICS AND DISSEMINATION: Ethical and health research authority approval was obtained in January 2018. All data will be collected by 2025. Full trial results will be published in 2026. Secondary analyses of health economic data, biomarker studies and other translational work will be published subsequently. TRIAL REGISTRATION NUMBER: NCT03428477.

Preventative behaviours and COVID-19 infection in a Canadian cohort of people living with HIV.

Few studies have examined preventative behaviour practices with respect to COVID-19 among people living with HIV (human immunodeficiency virus). Using a cross-sectional survey from a Canadian Institutes of Health Research Canadian HIV Trials Network study (CTN 328) of people living with HIV on vaccine immunogenicity, we examined the relationships between participant characteristics and behavioural practices intended to prevent COVID-19 infection. Participants living in four Canadian urban centers were enrolled between April 2021-January 2022, at which time they responded to a questionnaire on preventative behaviour practices. Questionnaire and clinical data were combined to explore relationships between preventive behaviours and (1) known COVID-19 infection pre-enrolment, (2) multimorbidity, (3) developing symptomatic COVID-19 infection, and (4) developing symptomatic COVID-19 infection during the Omicron wave. Among 375 participants, 49 had COVID-19 infection pre-enrolment and 88 post-enrolment. The proportion of participants reporting always engaging in preventative behaviours included 87% masking, 79% physical distancing, 70% limiting social gatherings, 65% limiting contact with at-risk individuals, 33% self-isolating due to symptoms, and 26% self-quarantining after possible exposure. Participants with known COVID-19 infection pre-enrolment were more likely to self-quarantine after possible exposure although asymptomatic (65.0% vs 23.4%, p < 0.001; Chi-square test). Participants with multiple comorbidities more likely endorsed physical distancing (85.7% vs 75.5%, p = 0.044; Chi-square test), although this was not significant in logistic regression analysis adjusted for age, sex, race, number of household members, number of bedrooms/bathrooms in the household per person, influenza immunization, and working in close physical proximity to others. Overall, participants reported frequent practice of preventative behaviours.

Polymorphisms in Cyclooxygenase, Lipoxygenase, and TP53 Genes Predict Colorectal Polyp Risk Reduction by Aspirin in the seAFOod Polyp Prevention Trial.

Aspirin and eicosapentaenoic acid (EPA) reduce colorectal adenomatous polyp risk and affect synthesis of oxylipins including prostaglandin E2. We investigated whether 35 SNPs in oxylipin metabolism genes such as cyclooxygenase (PTGS) and lipoxygenase (ALOX), as well as 7 SNPs already associated with colorectal cancer risk reduction by aspirin (e.g., TP53; rs104522), modified the effects of aspirin and EPA on colorectal polyp recurrence in the randomized 2 × 2 factorial seAFOod trial. Treatment effects were reported as the incidence rate ratio (IRR) and 95% confidence interval (CI) by stratifying negative binomial and Poisson regression analyses of colorectal polyp risk on SNP genotype. Statistical significance was reported with adjustment for the false discovery rate as the P and q value. 542 (of 707) trial participants had both genotype and colonoscopy outcome data. Reduction in colorectal polyp risk in aspirin users compared with nonaspirin users was restricted to rs4837960 (PTGS1) common homozygotes [IRR, 0.69; 95% confidence interval (CI), 0.53-0.90); q = 0.06], rs2745557 (PTGS2) compound heterozygote-rare homozygotes [IRR, 0.60 (0.41-0.88); q = 0.06], rs7090328 (ALOX5) rare homozygotes [IRR 0.27 (0.11-0.64); q = 0.05], rs2073438 (ALOX12) common homozygotes [IRR, 0.57 (0.41-0.80); q = 0.05], and rs104522 (TP53) rare homozygotes [IRR, 0.37 (0.17-0.79); q = 0.06]. No modification of colorectal polyp risk in EPA users was observed. In conclusion, genetic variants relevant to the proposed mechanism of action on oxylipins are associated with differential colorectal polyp risk reduction by aspirin in individuals who develop multiple colorectal polyps. SNP genotypes should be considered during development of personalized, predictive models of colorectal cancer chemoprevention by aspirin. PREVENTION RELEVANCE: Single-nucleotide polymorphisms in genes controlling lipid mediator signaling may modify the colorectal polyp prevention activity of aspirin. Further investigation is required to determine whether testing for genetic variants can be used to target cancer chemoprevention by aspirin to those who will benefit most.

Hepatitis B care cascade among people with HIV/HBV coinfection in the North American AIDS Cohort Collaboration on Research and Design, 2012-2016.

A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step.

Antibody neutralization capacity after coronavirus disease 2019 vaccination in people with HIV in Canada.

OBJECTIVES: Many vaccines require higher/additional doses or adjuvants to provide adequate protection for people with HIV (PWH). Here, we compare coronavirus disease 2019 (COVID-19) vaccine-induced antibody neutralization capacity in PWH vs. HIV-negative individuals following two vaccine doses. DESIGN: In Canadian prospective observational cohorts, including a multicentre study of PWH receiving at least two COVID-19 vaccinations (mRNA or ChAdOx1-S), and a parallel study of HIV-negative controls (Stop the Spread Ottawa Cohort), we measured vaccine-induced neutralization capacity 3 months post dose 2 (±1 month). METHODS: COVID-19 neutralization efficiency was measured by calculating the half maximal inhibitory dilution (ID50) using a high-throughput protein-based neutralization assay for Ancestral (Wuhan), Delta and Omicron (BA.1) spike variants. Univariable and multivariable quantile regression were used to compare COVID-19-specific antibody neutralization capacity by HIV status. RESULTS: Neutralization assays were performed on 256 PWH and 256 controls based on specimen availability at the timepoint of interest, having received two vaccines and known date of vaccination. There was a significant interaction between HIV status and previous COVID-19 infection status in median ID50. There were no differences in median ID50 for HIV+ vs. HIV-negative persons without past COVID-19 infection. For participants with past COVID-19 infection, median ICD50 was significantly higher in controls than in PWH for ancestral SARS-CoV-2 and Omicron variants, with a trend for the Delta variant in the same direction. CONCLUSION: Vaccine-induced SARS-CoV-2 neutralization capacity was similar between PWH vs. HIV-negative persons without past COVID-19 infection, demonstrating favourable humoral-mediated immunogenicity. Both HIV+ and HIV-negative persons demonstrated hybrid immunity. TRIAL REGISTRATION: clinicaltrials.gov NCT04894448.

Colorectal polyp outcomes after participation in the seAFOod polyp prevention trial: Evidence of rebound elevated colorectal polyp risk after short-term aspirin use.

BACKGROUND: The seAFOod polyp prevention trial was a randomised, placebo-controlled, 2 × 2 factorial trial of aspirin 300 mg and eicosapentaenoic acid (EPA) 2000 mg daily in individuals who had a screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Aspirin treatment was associated with a 20% reduction in colorectal polyp number at BCSP surveillance colonoscopy 12 months later. It is unclear what happens to colorectal polyp risk after short-term aspirin use. AIM: To investigate colorectal polyp risk according to the original trial treatment allocation, up to 6 years after trial participation. METHODS: All seAFOod trial participants were scheduled for further BCSP surveillance and provided informed consent for the collection of colonoscopy outcomes. We linked BCSP colonoscopy data to trial outcomes data. RESULTS: In total, 507 individuals underwent one or more colonoscopies after trial participation. Individuals grouped by treatment allocation were well matched for clinical characteristics, follow-up duration and number of surveillance colonoscopies. The polyp detection rate (PDR; the number of individuals who had ≥1 colorectal polyp detected) after randomization to placebo aspirin was 71.1%. The PDR was 80.1% for individuals who had received aspirin (odds ratio [OR] 1.13 [95% confidence interval 1.02, 1.24]; p = 0.02). There was no difference in colorectal polyp outcomes between individuals who had been allocated to EPA compared with its placebo (OR for PDR 1.00 [0.91, 1.10]; p = 0.92). CONCLUSION: Individuals who received aspirin in the seAFOod trial demonstrated increased colorectal polyp risk during post-trial surveillance. Rebound elevated neoplastic risk after short-term aspirin use has important implications for aspirin cessation driven by age-related bleeding risk. ISRCTN05926847.

Reinfection incidence and risk among people treated for recent hepatitis C virus infection.

OBJECTIVE: Reinfection poses a challenge to hepatitis C virus (HCV) elimination. This analysis assessed incidence of, and factors associated with reinfection among people treated for recent HCV (duration of infection <12 months). METHODS: Participants treated for recent HCV (primary infection or reinfection) in an international randomized trial were followed at 3-monthly intervals for up to 2 years to assess for reinfection. Reinfection incidence was calculated using person-time of observation. Factors associated with HCV reinfection were assessed using Cox proportional hazards regression analysis. RESULTS: Of 222 participants treated for recent HCV, 196 (62% primary infection, 38% reinfection) were included in the cohort at risk for reinfection, of whom 87% identified as gay or bisexual men, 71% had HIV and 20% injected drugs in the month prior to enrolment. During 198 person-years of follow-up, 28 cases of HCV reinfection were identified among 27 participants, for an incidence of 14.2 per 100 person-years [95% confidence interval (CI) 9.8-20.5]. Reinfection was associated with prior HCV reinfection [adjusted hazards ratio (aHR) 2.42; 95% CI 1.08-5.38], injection drug use posttreatment (aHR 2.53; 95% CI 1.14-5.59), condomless anal intercourse with casual male partners (aHR 3.32; 95% CI 1.14-9.65) and geographic region (United Kingdom, aHR 0.21; 95% CI 0.06-0.75). Among gay and bisexual men (GBM), reinfection was also associated with sexualized drug use involving injecting posttreatment (aHR 2.97; 95% CI 1.10-8.02). CONCLUSION: High reinfection incidence following treatment for recent HCV among people with ongoing sexual and drug use risk behaviour highlights the need for posttreatment surveillance, rapid retreatment of reinfection and targeted harm reduction strategies.

Reasons for not using pre-exposure prophylaxis for HIV and strategies that may facilitate uptake in Ontario and British Columbia among gay, bisexual and other men who have sex with men: a cross-sectional survey.

BACKGROUND: Pre-exposure prophylaxis (PrEP) for HIV is underutilized. We aimed to identify barriers to use of PrEP and strategies that may facilitate its uptake. METHODS: Gay, bisexual and other men who have sex with men, aged 19 years or older and living in Ontario and British Columbia, Canada, completed a cross-sectional survey in 2019-2020. Participants who met Canadian PrEP guideline criteria and were not already using PrEP identified relevant barriers and which strategies would make them more likely to start PrEP. We described the barriers and strategies separately for Ontario and BC. RESULTS: Of 1527 survey responses, 260 respondents who never used PrEP and met criteria for PrEP were included. In Ontario, the most common barriers were affordability (43%) and concern about adverse effects (42%). In BC, the most common reasons were concern about adverse effects (41%) and not feeling at high enough risk (36%). In Ontario, preferred strategies were short waiting time (63%), the health care provider informing about their HIV risk being higher than perceived (62%), and a written step-by-step guide (60%). In BC, strategies were short waiting time (68%), people speaking publicly about PrEP (68%), and the health care provider counselling about their HIV risk being higher than perceived (64%), adverse effects of PrEP (65%) and how well PrEP works (62%). INTERPRETATION: Concern about adverse effects and not self-identifying as having high risk for HIV were common barriers, and shorter waiting times may increase PrEP uptake. In Ontario, the findings suggested lack of affordability, whereas in BC, strategies involving health care providers were valued.

Disjuncture between self-perceived and clinically assessed risk of HIV among gay, bisexual, and other men who have sex with men in Ontario and British Columbia, Canada.

BACKGROUND: Self-perceived and clinically assessed HIV risk do not always align. We compared self-perceived and clinically assessed risk of HIV and the reasons for self-perceived low risk of HIV among gay, bisexual, and other men who have sex with men (GBM) from large urban centers in Ontario and British Columbia, Canada. METHODS: Never PrEP users recruited from sexual health clinics or online, completed a cross-sectional survey between July/2019 and August/2020. We contrasted self-perceived HIV risk against criteria from the Canadian PrEP guidelines and participants were categorized as concordant or discordant. We used content analysis to categorize participants' free-text explanations for perceived low HIV risk. These were compared with answers to quantitative responses about condomless sex acts and number of partners. RESULTS: Of 315 GBM who self-perceived low risk of HIV, 146 (46%) were considered at high risk according to the guidelines. Participants with discordant assessment were younger, had less years of formal education, were more often in an open relationship and were more likely to self-identify as gay. Reasons for self-perceived low HIV risk in the discordant group were condom use (27%), being in a committed relationship/having one main partner (15%), having no or infrequent anal sex (12%) and having few partners (10%). CONCLUSIONS: There is a disjuncture between self-perceived and clinically assessed risk of HIV. Some GBM may underestimate their HIV risk and clinical criteria may overestimate risk. Bridging these gaps requires efforts to increase HIV risk awareness in the community, and refinement of clinical assessments based on individualized discussions between the provider and the user.

Injectable Pre-Exposure Prophylaxis for HIV Prevention: Perspectives on the Benefits and Barriers from Gay, Bisexual, and Queer Men and Health System Stakeholders in Ontario, Canada.

One hope surrounding long-acting HIV pre-exposure prophylaxis (PrEP) is reaching new users who could most benefit, as well as improving the experiences of oral PrEP users who may desire to switch modalities. Gay, bisexual, queer, and other men who have sex with men (GBQM) continue to make up over half of new HIV diagnoses in Canada, and oral PrEP uptake has plateaued among this population. Approval of injectable PrEP is anticipated, but there is a paucity of research to inform health promotion and implementation. Between June and October 2021, we conducted 22 in-depth interviews with GBQM oral PrEP users and non-PrEP users living in Ontario, Canada. We also conducted small focus groups or individual interviews with 20 key stakeholders (health care providers, public health officials, community-based organization staff). Interviews were audio recorded, transcribed verbatim, and analyzed in NVivo using thematic analysis. Only about one-third of GBQM had heard of injectable PrEP. Many PrEP users perceived greater convenience, adherence, and confidentiality with injectable PrEP. Some PrEP users did not anticipate switching because of needle discomfort or feeling more "in control" with oral PrEP. None of the non-PrEP users said that injectable PrEP would make them start PrEP. Injectable PrEP may offer additional convenience for GBQM; however, it did not appear to affect participants' PrEP decision-making significantly. Stakeholders noted that injectable PrEP may improve access, support adherence, and benefit marginalized groups. Some clinicians expressed concerns about the time/personnel required to make injectable PrEP available. System-level challenges in implementing injectable PrEP, including cost, must also be addressed.

Gay, bisexual, and queer men's confidence in the Undetectable equals Untransmittable HIV prevention message: longitudinal qualitative analysis of the sexual decision-making of pre-exposure prophylaxis users over time.

BACKGROUND: Our objective was to understand what gay, bisexual, and queer men (GBQM) who had experience using pre-exposure prophylaxis (PrEP) thought about the 'Undetectable equals Untransmittable' (U=U) message and how it informed their sexual decision-making over time. METHODS: We conducted annual longitudinal qualitative interviews (2020-22) with 17 current or former PrEP users as part of a mixed-methods implementation science study examining barriers and facilitators to PrEP awareness, access, and adherence. Over 3years, 47 interviews were conducted with GBQM in Ontario, Canada. Interviews were transcribed verbatim and coded in NVivo following reflexive thematic analysis. RESULTS: Participants' sexual health decision-making was informed by their confidence in biomedical HIV prevention and the person taking medication (i.e. themselves using PrEP versus a real/imagined person living with HIV (PLHIV)). Longitudinal narratives of U=U clustered around four overarching themes: (1) U=U confidence (i.e. increasing trust in U=U irrespective of their PrEP use); (2) PrEP confidence (i.e. accounts of self-reliance and PrEP as sufficient HIV protection); (3) combination confidence (i.e. trusting U=U and PrEP as a package); and (4) partner confidence (i.e. potential 'distrust' of U=U due to uncertainties about partners' medication adherence). Overall, men described increased sex with PLHIV over time, including some participants who, during earlier interviews, said they would 'never be comfortable' with serodifferent sexual partners. CONCLUSIONS: GBQM's use of PrEP shaped how they thought about U=U and sex with PLHIV. Although many GBQM embraced treatment as prevention/U=U as significant to their sexual lives, longitudinal analysis revealed its varied and uneven adoption across participants and time.

Process description of developing HIV prevention monitoring indicators for a province-wide pre-exposure prophylaxis (PrEP) program in British Columbia, Canada.

In 2018, the pre-exposure prophylaxis (PrEP) program was initiated in British Columbia (BC), Canada, providing PrEP at no cost to qualifying residents. This observational study discussed the steps to develop key evidence-based monitoring indicators and their calculation using real-time data. The indicators were conceptualized, developed, assessed and approved by the Technical Monitoring Committee of representatives from five health authority regions in BC, the BC Ministry of Health, the BC Centre for Disease Control, and the BC Centre for Excellence in HIV/AIDS. Indicator development followed the steps adopted from the United States Centers for Disease Control and Prevention framework for program evaluation in public health. The assessment involved eight selection criteria: data quality, indicator validity, existing scientific evidence, indicator informativeness, indicator computing feasibility, clients' confidentiality maintenance capacity, indicator accuracy, and administrative considerations. Clients' data from the provincial-wide PrEP program (January 2018-December 2020) shows the indicators' calculation. The finalized 14 indicators included gender, age, health authority, new clients enrolled by provider type and by the health authority, new clients dispensed PrEP, clients per provider, key qualifying HIV risk factor(s), client status, PrEP usage type, PrEP quantity dispensed, syphilis and HIV testing and incident cases, and adverse drug reaction events. Cumulative clients' data (n = 6966; 99% cis-gender males) identified an increased new client enrollment and an unexpected drop during the COVID-19 pandemic. About 80% dispensed PrEP from the Vancouver Coastal health authority. The HIV incidence risk index for men who have sex with men score ≥10 was the most common qualifying risk factor. The framework we developed integrating indicators was applied to monitor our PrEP program, which could help reduce the public health impact of HIV.

The rate of hepatitis C reinfection in Canadians coinfected with HIV and its implications for national elimination.

BACKGROUND: The World Health Organisation (WHO) has set targets for the rate of new infections as a way to measure progress towards the elimination of hepatitis C virus (HCV) as a public health threat. As more people are successfully treated for HCV, a higher proportion of new infections will be reinfections. We consider whether the reinfection rate has changed since the interferon era and what we can infer about national elimination efforts from the current reinfection rate. METHODS: The Canadian Coinfection Cohort is representative of HIV HCV coinfected people in clinical care. We selected cohort participants successfully treated for a primary HCV infection either in the interferon era or in the era of direct acting antivirals (DAAs). Selected participants were followed from 12 weeks after completing a successful treatment until the end of 2019 or until their last measured HCV RNA. We estimated the reinfection rate in each treatment era, overall and in participant subgroups, using proportional hazard models appropriate for interval censored data. RESULTS: Among 814 successfully treated participants with additional HCV RNA measurements, there were 62 reinfections. The overall reinfection rate was 2.6 (95% confidence interval, CI, 1.2-4.1) /100 person years (PY) in the interferon era and 3.4 (95% CI 2.5-4.4) /100 PY in the DAA era. The rate in those reporting injection drug use (IDU) was much higher: 4.7 (95% CI 1.4-7.9) /100 PY and 7.6 (95% CI 5.3-10) /100 PY in the interferon and DAA eras respectively. CONCLUSION: The overall reinfection rate in our cohort is now above the WHO target set for new infections in people who inject drugs. The reinfection rate in those reporting IDU has increased since the interferon era. This suggests Canada is not on track to achieve HCV elimination by 2030.

Identifying Longitudinal CD4:CD8 Ratio Trajectories Indicative of Chronic Renal Disease Risk among People Living with HIV: An Application of Growth Mixture Models.

The incidence of chronic kidney disease (CKD) is increasing among people living with HIV (PLWH). Routine monitoring of indicators such as CD4:CD8 ratio might improve the early detection of CKD. Our objective was to identify clinically relevant CD4:CD8 ratio trajectories indicative of CKD risk. Participants were ≥ 18 years old, initiated antiretroviral therapy between 2000 and 2016, and were followed for ≥6 months until 31 March 2017 or last contact date. Outcome was incidence of CKD. Growth mixture models (GMMs) and decay models were used to compare CD4:CD8 ratio trajectories. Following GMM, 4547 (93.5%) participants were classified in Class 1 with 5.4% developing CKD, and 316 (6.5%) participants were classified in Class 2 with 20.9% developing CKD. The final model suggested that participants in Class 2 had 8.72 times the incidence rate of developing CKD than those in Class 1. Exponential decay models indicated a significant CD4:CD8 ratio decline among Class 2 participants who developed CKD. Among those who developed CKD in Class 2, starting at 5.5 years of follow-up, the slope of their ratio trajectory curve changed significantly, and the rate of decline increased dramatically. Routine monitored CD4:CD8 ratios can be an effective strategy to identify early CKD risk among PLWH.