Integrated supervised consumption services and hepatitis C testing and treatment among people who inject drugs in Toronto, Canada: A cross-sectional analysis.

Despite the availability of publicly funded hepatitis C (HCV) treatment in Canada, treatment gaps persist, particularly among people who inject drugs. We estimate correlates of HCV care cascade engagement (testing, diagnosis, and treatment) among people who inject drugs in Toronto, Canada and examine the effect of accessing differing supervised consumption service (SCS) models on self-reported HCV testing and treatment. This is a cross-sectional baseline analysis of 701 people who inject drugs surveyed in the Toronto, Ontario integrated Supervised Injection Services (OiSIS-Toronto) study between November 2018 and March 2020. We examine correlates of self-reported HCV care cascade outcomes including SCS model, demographic, socio-structural, drug use, and harm reduction characteristics. Overall, 647 participants (92%) reported ever receiving HCV testing, of whom 336 (52%) had been diagnosed with HCV. Among participants who reported ever being diagnosed with HCV, 281 (84%) reported chronic HCV, of whom 130 (46%) reported HCV treatment uptake and 151 (54%) remained untreated. Compared to those with no SCS use, participants who had ever injected at an integrated SCS model with co-located HCV care had greater prevalence of both ever receiving HCV testing (adjusted prevalence ratio [aPR]: 1.12, 95% confidence interval [CI]: 1.02-1.24) and ever receiving HCV treatment (aPR: 1.67, 95% CI: 1.04-2.69). Over half of participants diagnosed with chronic HCV reported remaining untreated. Our findings suggest that integrated SCS models with co-located HCV care represent key strategies for linkage to HCV care, but that more is needed to support scale-up.

Chemsex and incidence of sexually transmitted infections among Canadian pre-exposure prophylaxis (PrEP) users in the l'Actuel PrEP Cohort (2013-2020).

OBJECTIVES: Use of illicit substances during sex (chemsex) may increase transmission of HIV and other STIs. Pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV transmission, providing an important prevention tool for those who practise chemsex. However, it does not prevent acquisition of other STIs. We aim to examine the impact of chemsex on STI incidence among gay, bisexual and other men who have sex with men (gbMSM), and transgender women using PrEP in Montréal, Canada. METHODS: We linked baseline sociodemographic and behavioural data with follow-up STI testing from 2013 to 2020 among PrEP users in the l'Actuel PrEP Cohort (Canada). Focusing on the 24 months following PrEP initiation, we estimated the effect of chemsex reported at baseline on cumulative incidence of gonorrhoea and chlamydia using Kaplan-Meier curves and survival analyses. We investigated the role of polysubstance use and effect modification by sociodemographic factors. RESULTS: There were 2086 clients (2079 cisgender gbMSM, 3 transgender gbMSM, 4 transgender women) who initiated PrEP, contributing 1477 years of follow-up. There were no incident HIV infections among clients on PrEP. Controlling for sociodemographic confounders, clients reporting chemsex at baseline had a 32% higher hazard of gonorrhoea/chlamydia diagnosis (adjusted HR=1.32; 95% CI: 1.10 to 1.57), equivalent to a risk increase of 8.9 percentage points (95% CI: 8.5 to 9.4) at 12 months. The effect was greater for clients who reported polysubstance use (adjusted HR=1.51; 95% CI: 1.21 to 1.89). The strength of the effect of chemsex on STI incidence varied by age, education and income. CONCLUSION: Among PrEP users, chemsex at baseline was linked to increased incidence of gonorrhoea and chlamydia. This effect was stronger for people reporting multiple chemsex substances. The high STI incidence among gbMSM who report chemsex highlights the importance of PrEP for this population and the need for integrated services that address the complexities of sexualised substance use.

The Ontario Integrated Supervised Injection Services Cohort Study of People Who Inject Drugs in Toronto, Canada (OiSIS-Toronto): Cohort Profile.

The Ontario Integrated Supervised Injection Services cohort in Toronto, Canada (OiSIS-Toronto) is an open prospective cohort of people who inject drugs (PWID). OiSIS-Toronto was established to evaluate the impacts of supervised consumption services (SCS) integrated within three community health agencies on health status and service use. The cohort includes PWID who do and do not use SCS, recruited via self-referral, snowball sampling, and community/street outreach. From 5 November 2018 to 19 March 2020, we enrolled 701 eligible PWID aged 18+ who lived in Toronto. Participants complete interviewer-administered questionnaires at baseline and semi-annually thereafter and are asked to consent to linkages with provincial healthcare administrative databases (90.2% consented; of whom 82.4% were successfully linked) and SCS client databases. At baseline, 86.5% of participants (64.0% cisgender men, median ([IQR] age= 39 [33-49]) had used SCS in the previous 6 months, of whom most (69.7%) used SCS for <75% of their injections. A majority (56.8%) injected daily, and approximately half (48.0%) reported fentanyl as their most frequently injected drug. As of 23 April 2021, 291 (41.5%) participants had returned for follow-up. Administrative and self-report data are being used to (1) evaluate the impact of integrated SCS on healthcare use, uptake of community health agency services, and health outcomes; (2) identify barriers and facilitators to SCS use; and (3) identify potential enhancements to SCS delivery. Nested sub-studies include evaluation of "safer opioid supply" programs and impacts of COVID-19.

A National Survey of Canadian Physicians on HPV: Knowledge, Barriers, and Preventive Practices.

OBJECTIVE: Physicians are the sole prescribers of the human papillomavirus (HPV) vaccine for adults in Canada. This survey of Canadian physicians aimed to explore knowledge, barriers, and preventive practices regarding HPV vaccination. METHOD: A survey of general practitioners (GPs) (n = 337) and obstetrician/gynaecologists (OB/GYNs) (n = 81) was conducted in May and June 2016 using an online panel. Demographic data and information pertaining to HPV knowledge, attitudes, and vaccination practices were collected by using a 22-item questionnaire. RESULTS: A total of 83% of GPs recommended or administered HPV vaccine to adults. Among physicians, 99% to 100% strongly agreed that vaccination is an important aspect of disease prevention. Physicians were rarely concerned about vaccine safety (5%-11%). Cost was seen as the number one barrier by 92% to 95% of physicians. Physicians rated consumers' understanding of HPV to be low (11%-14%, very good; and 49%-56%, somewhat good knowledge). Among physicians, 60% to 66% of said they routinely discussed HPV vaccination with patients. Female physicians demonstrated greater knowledge of HPV than their male counterparts. CONCLUSION: GPs and obstetrician/gynaecologists routinely recommend and administer the HPV vaccine to patients. The majority of physicians showed high levels of knowledge regarding HPV vaccine and associated cancers; however, perceived barriers of cost may limit recommendations for vaccination, particularly among older women or men.

A National Survey of Canadian Adults on HPV: Knowledge, Attitudes, and Barriers to the HPV Vaccine.

OBJECTIVE: Identifying human papillomavirus (HPV) vaccination motivators and barriers among adults could lead to new approaches to improve HPV vaccination rates in non-pediatric populations. This Canadian survey aimed to assess current knowledge of, attitudes towards, and barriers to the HPV vaccine among the general public. METHODS: An online panel was used to survey HPV unvaccinated women (n = 802) and vaccinated women (n = 250) 18 to 45 years old, as well as 18- to 26-year-old men (n = 200), in May and June 2016. A 16-item questionnaire collected data on sociodemographic factors, health-seeking behaviours, knowledge of HPV infection and its consequences, and the HPV vaccine. Data were stratified by sex and by vaccination status among women. RESULTS: The majority of individuals somewhat or strongly agreed that vaccination is an important aspect of disease prevention (vaccinated women, 93%; unvaccinated women, 85%; and men, 59%). However, a high proportion of patients were concerned about vaccine safety (vaccinated women, 26%; unvaccinated women, 40%; and men, 36%). Moreover, 58% to 61% of participants were generally cautious about taking any vaccine. The number one reported barrier to vaccination was not having a recommendation from a doctor (38%). Cost was seen as a barrier by only 18% to 20% of participants. CONCLUSION: Canadian participants show a broad diversity in HPV knowledge and regarding barriers to vaccination. The youngest populations (vaccinated women and men) showed higher levels of knowledge regarding HPV.

Does hormonal therapy for fertility preservation affect the survival of young women with early-stage endometrial cancer?

BACKGROUND: The incidence of endometrial cancer among young women is increasing. Some patients with low-grade endometrial cancer receive hormone therapy (HT) before surgery to preserve fertility. It is unclear whether this adversely affects survival. METHODS: Patients with localized, low-grade endometrial cancer who were aged <45 years were selected from the Surveillance, Epidemiology, and End Results database between 1993 and 2012. Propensity score matching was used to select comparable groups receiving HT or primary surgery. Cancer-specific and overall survival were measured using Kaplan-Meier methods. Hazard ratios and 95% confidence intervals (95% CIs) were estimated using Cox models adjusted for age, period of diagnosis, marital status, race, tumor grade, morphology, and previous radiotherapy. RESULTS: A total of 6339 women were included in the current study cohort, 161 of whom initially received HT and 6178 of whom received primary surgery. After 15 years of follow-up, all-cause mortality did not differ between the groups (HT group: 14.1% [95% CI, 6.7%-28.4%] and propensity score-matched primary surgery group: 9.3% [95% CI, 4.1%-20.5%]). Cancer-specific mortality appeared higher in patients treated with HT compared with those treated with primary surgery (9.2% [95% CI, 3.4%-24.0%] vs 2.1% [95% CI, 1.5%-2.8%]). However, this difference was driven by 3 late deaths in the HT group. Sensitivity analyses using a broader definition of cancer-specific mortality provided no statistical evidence of a survival difference between the treatment groups. The hazard ratio for the overall risk of death was 1.45 (95% CI, 0.44-4.74). CONCLUSIONS: Based on this population-based cohort, young patients with low-grade endometrial cancer appear to have excellent survival, regardless of the primary therapy chosen (HT vs primary surgery). The current selection of patients for HT to preserve fertility, which is managed carefully by experienced clinicians, does not appear to significantly worsen clinical outcomes. Cancer 2017;123:1545-1554. © 2017 American Cancer Society.

Recurrence of Human Papillomavirus External Genital Wart Infection Among High-Risk Adults in Montréal, Canada.

OBJECTIVES: The incidence of recurrent genital warts is not well characterized; this is especially true in a post-human papillomavirus (HPV) vaccination era. The objectives of this study were to assess the incidence of subsequent HPV-related external genital warts (EGW) episodes in high-risk male and female adults, as well as ascertain patient profile and disease characteristics, in a real-world Canadian sexual health clinical setting. METHODS: Retrospective chart review study conducted at Clinique médicale l'Actuel, a sexual health clinic in Montréal, Québec, Canada. Eligible patients were 18 to 45 years of age with a first diagnosis of EGW associated with a HPV infection between July 1, 2006, and June 30, 2012. RESULTS: A total of 400 first-episode EGW cases were identified. Up to 6 subsequent episodes were documented, with 194 (48.5%) patients reporting at least 1 subsequent EGW episode. Median time to first subsequent EGW episode was 3.97 years, and the incidence density rate for all subsequent episodes was 0.18/100 patient-years. Over 90% of patients reported clearance of the first subsequent episode, with median time to clearance of 0.30 years. Regardless of subsequent episode number, greater than 95% of patients received treatment, primarily cryotherapy, with high-risk sexual behavior reducing as number of episodes increased. CONCLUSIONS: Overall, a high rate of subsequent EGW episodes was observed in this high-risk population, despite high treatment rates and improvement in high-risk sexual behavior. These data, assessed in a prevaccination Québec health care system, may be compared with future EGW rates to assess the impact of a governmentally-funded HPV vaccination program.

Validation of case-ascertainment algorithms using health administrative data to identify people who inject drugs in Ontario, Canada.

OBJECTIVES: Health administrative data can be used to improve the health of people who inject drugs by informing public health surveillance and program planning, monitoring, and evaluation. However, methodological gaps in the use of these data persist due to challenges in accurately identifying injection drug use (IDU) at the population level. In this study, we validated case-ascertainment algorithms for identifying people who inject drugs using health administrative data in Ontario, Canada. STUDY DESIGN AND SETTING: Data from cohorts of people with recent (past 12 months) IDU, including those participating in community-based research studies or seeking drug treatment, were linked to health administrative data in Ontario from 1992 to 2020. We assessed the validity of algorithms to identify IDU over varying look-back periods (ie, all years of data [1992 onwards] or within the past 1-5 years), including inpatient and outpatient physician billing claims for drug use, emergency department (ED) visits or hospitalizations for drug use or injection-related infections, and opioid agonist treatment (OAT). RESULTS: Algorithms were validated using data from 15,241 people with recent IDU (918 in community cohorts and 14,323 seeking drug treatment). An algorithm consisting of ≥1 physician visit, ED visit, or hospitalization for drug use, or OAT record could effectively identify IDU history (91.6% sensitivity and 94.2% specificity) and recent IDU (using 3-year look back: 80.4% sensitivity, 99% specificity) among community cohorts. Algorithms were generally more sensitive among people who inject drugs seeking drug treatment. CONCLUSION: Validated algorithms using health administrative data performed well in identifying people who inject drugs. Despite their high sensitivity and specificity, the positive predictive value of these algorithms will vary depending on the underlying prevalence of IDU in the population in which they are applied.

Rapid hepatitis C virus point-of-care RNA testing and treatment at an integrated supervised consumption service in Toronto, Canada: a prospective, observational cohort study.

Background: Despite high burden of Hepatitis C (HCV) among people who inject drugs, significant barriers to care persist. The aim of this study was to evaluate the provision of rapid, low-barrier point-of-care (POC) HCV RNA testing and linkage to care among clients of a supervised consumption service (SCS) located within a community health centre in Toronto, Canada. Secondary aims included measuring HCV RNA prevalence at baseline, HCV incidence during follow-up and exploring factors associated with HCV RNA positivity and treatment uptake. Methods: Participants were enrolled in a prospective, observational cohort from August 13, 2018 to September 30, 2021. Those with positive HCV RNA tests were offered immediate referral to onsite treatment. Those with negative results were offered repeat testing every three months for up to four visits. HCV incidence was estimated as the number of incident HCV infections per 100 person-years at risk, among those HCV RNA negative at baseline who returned for ≥1 follow-up visit. Missing data were reported when present. Findings: 128 participants were enrolled with four later removed due to ineligibility. At baseline, 54 of 124 eligible participants (43.5%) tested HCV RNA positive. HCV incidence was 35.1 cases per 100 person-years (95% CI: 18.9-65.3) with a cumulative incidence of 38.3% at 15 months of follow-up. Among participants HCV RNA positive at baseline or follow-up (n = 64), 67.2% (n = 43) were linked to HCV care and treatment was initiated among 67.4% (n = 29/43). Interpretation: High HCV RNA prevalence and incidence demonstrate that the SCS serves a high-risk population for HCV. Testing acceptance was high, as was treatment engagement. POC HCV RNA testing positions SCSs as an important point of HCV care access. Funding: HCV Micro-Elimination Grant, Gilead Sciences Canada; in-kind support from Cepheid.

Chemsex practices and pre-exposure prophylaxis (PrEP) trajectories among individuals consulting for PrEP at a large sexual health clinic in Montréal, Canada (2013-2020).

INTRODUCTION: Chemsex among gay, bisexual and other men who have sex with men (gbMSM) has raised public health concerns because of its association with sexual behaviours that can increase transmission of sexually transmitted infections, including HIV. Pre-exposure prophylaxis (PrEP) is highly effective at blocking HIV acquisition, addressing important prevention needs among individuals practicing chemsex. This study aims to improve our understanding of chemsex practices and PrEP trajectories of gbMSM and transgender women consulting for PrEP. METHODS: We used data from the PrEP cohort of Clinique médicale l'Actuel, a major sexual health clinic in Montréal. We describe the sociodemographic profile of clients consulting for PrEP, characterize chemsex and polysubstance use trends over time, and evaluate PrEP trajectories using Kaplan-Meier curves. RESULTS: Among 2923 clients who consulted for PrEP between 2013-2020 (2910 cisgender gbMSM, 6 transgender gbMSM, 7 transgender women), 24 % reported chemsex in the past year and 13 % reported polysubstance use. The most common chemsex substances were ecstasy (14 %), GHB (13 %), and cocaine (12 %). The proportion of clients reporting chemsex and polysubstance use decreased over time. In both the chemsex and no-chemsex group, 73 % of clients initiated PrEP. The median time to discontinuation was similar between the chemsex (6.5 months; 95 %CI: 5.3-7.2) and no-chemsex group (6.9 months; 95 %CI: 6.3-7.5). CONCLUSION: Chemsex is not a barrier to PrEP initiation or persistence. However, these results suggest a high prevalence of chemsex among gbMSM consulting for PrEP, highlighting the need for services addressing the intersection of sexual health and substance use for this population.

Is Hodgkin Lymphoma Associated with Hepatitis B and C Viruses? A Systematic Review and Meta-analysis.

BACKGROUND: Apart from the Epstein-Barr virus (EBV), the etiology of the hematologic malignancy Hodgkin lymphoma (HL) is not well defined. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with some lymphoproliferative diseases with similarities to HL. METHODS: We performed a systematic review and meta-analysis, by searching Embase, MEDLINE, and Web of Science databases on March 9, 2021, for studies reporting a measure of association for HBV and HL or HCV and HL. We calculated pooled relative risks (RR) and their 95% confidence intervals (CI). RESULTS: Pooling nine HBV studies with 1,762 HL cases yielded an RR of 1.39 (95% CI, 1.00-1.94) and pooling 15 HCV studies with 4,837 HL cases resulted in an RR of 1.09 (95% CI, 0.88-1.35). Meta-analyzing by study design, hepatitis detection method, and region revealed two subgroups with statistically significant associations-HCV studies that used hospital-based controls and/or were conducted in the West Pacific. No included study assessed age or EBV tumor status in relation to HL. CONCLUSIONS: Although we did not find an association between HBV or HCV and HL, research assessing the impact of age and EBV tumor status was lacking. IMPACT: The effect of HBV or HCV infection in the development of HL remains unclear.

The 9th Canadian Symposium on Hepatitis C Virus: Advances in HCV research and treatment towards elimination.

Hepatitis C virus (HCV) elimination has evolved into a coordinated global effort. Canada, with more than 250,000 chronically infected individuals, is among the countries leading this effort. The 9th Canadian Symposium on HCV, held in February 2020, thus established and addressed its theme, 'advances in HCV research and treatment towards elimination', by gathering together basic scientists, clinicians, epidemiologists, social scientists, and community members interested in HCV research in Canada. Plenary sessions showcased topical research from prominent international and national researchers, complemented by select abstract presentations. This event was hosted by the Canadian Network on Hepatitis C (CanHepC), with support from the Public Health Agency of Canada and the Canadian Institutes of Health Research and in partnership with the Canadian Liver Meeting. CanHepC has an established record in HCV research by its members and in its advocacy activities to address the care, treatment, diagnosis, and immediate and long-term needs of those affected by HCV infection. Many challenges remain in tackling chronic HCV infection, such as the need for a vaccine; difficult-to-treat populations and unknown aspects of patient subgroups, including pregnant women and children; vulnerable people; and issues distinct to Indigenous peoples. There is also increasing concern about long-term clinical outcomes after successful treatment, with the rise in comorbidities such as diabetes, cardiovascular disease, and fatty liver disease and the remaining risk for hepatocellular carcinoma in cirrhotic individuals. The symposium addressed these topics in highlighting research advances that will collectively play an important role in eliminating HCV and minimizing subsequent health challenges.

Epidemiology of varicella among immigrants and non-immigrants in Quebec, Canada, before and after the introduction of childhood varicella vaccination: a retrospective cohort study.

BACKGROUND: Many immigrants are susceptible to varicella on arrival to Canada because of different transmission dynamics in their countries of origin and scarcity of vaccination. Universal childhood vaccination programmes decrease varicella incidence rates through herd immunity, but the accumulating number of susceptible adult immigrants could remain at risk for severe varicella. Our aim was to describe the epidemiology of varicella among immigrants and non-immigrants before and after childhood varicella vaccination. METHODS: We did a population-based, retrospective cohort study of all varicella cases in Quebec, Canada, diagnosed between 1996 and 2014 in administrative health databases linked to immigration data. Cases of varicella met diagnostic codes in the International Classification of Diseases, Ninth and Tenth Revision Canadian modifications. Cases with a co-occurring zoster diagnostic code and immigrants from Australia, New Zealand, the USA, and western European countries were excluded. Vaccination periods included pre-vaccination (1996-98), private vaccination (1999-2005), and public vaccination (2006-14). Incidence rate and comparative rate ratios were estimated using census data. FINDINGS: A total of 231 339 varicella cases diagnosed between Jan 1, 1996, and Dec 31, 2014, were linked to 1 115 696 immigrants who arrived between Jan 1, 1980, and Dec 31, 2014. 1444 herpes zoster cases and 1276 immigrants from Australia, western Europe, New Zealand, and the USA were excluded. Among 228 619 varicella cases, 13 315 (5·8%) occurred in immigrants. In pre-vaccination versus public vaccination periods, varicella incidence declined in immigrants by 87% (95% CI 86·6-87·9; 324·3 cases per 100 000 person-years to 40·9 cases per 100 000 person-years) and in non-immigrants by 93% (92·4-92·7; 484 cases per 100 000 person-years to 36 cases per 100 000 person-years). Mean age at diagnosis increased in both groups (15·1 vs 19·4 years in immigrants and 8·4 vs 12·0 years in non-immigrants). In the public vaccination period, immigrants younger than 50 years had higher varicella rates than non-immigrants, with relative risk ranging from 1·53 (95% CI 1·37-1·72) to 4·64 (3·90-5·53) with the highest risk in adolescents and young adults, and people from Latin America and the Caribbean (age-specific incidence rate ratio [aIRR]I-NI pre-vaccination 2·19 and post-vaccination aIRRI-NI6·07) and south Asia (aIRRI-NI pre-vaccination 3·41 and aIRRI-NI post-vaccination 4·46) and in childbearing women (15-40 years; IRRI-NI 2·48). INTERPRETATION: Immigrant adolescents, young adults, and women of childbearing age had higher age-standardised rates of varicella than non-immigrants, with increasing disparities following vaccine introduction. Immigrants younger than 50 years of age would benefit from targeted vaccination upon arrival to host countries. FUNDING: The Canadian Institutes of Health Research and The Department of Medicine, Jewish General Hospital, Montreal, QC, Canada.

Pre-exposure Prophylaxis Uptake Among Men Who Have Sex With Men Who Used nPEP: A Longitudinal Analysis of Attendees at a Large Sexual Health Clinic in Montréal (Canada).

BACKGROUND: Reducing HIV transmission using pre-exposure prophylaxis (PrEP) requires focussing on individuals at high acquisition risk, such as men who have sex with men with a history of nonoccupational post-exposure prophylaxis (nPEP). This study aims to characterize longitudinal trends in PrEP uptake and its determinants among nPEP users in Montréal. METHODS: Eligible attendees at Clinique médicale l'Actuel were recruited prospectively starting in October 2000 (nPEP) and January 2013 (PrEP). Linking these cohorts, we characterized the nPEP-to-PrEP cascade, examined the determinants of PrEP uptake after nPEP consultation using a Cox proportional-hazard model, and assessed whether PrEP persistence differed by nPEP history using Kaplan-Meier curves. RESULTS: As of August 2019, 31% of 2682 nPEP cohort participants had 2 or more nPEP consultations. Subsequent PrEP consultations occurred among 36% of nPEP users, of which 17% sought nPEP again afterward. Among 2718 PrEP cohort participants, 46% reported previous nPEP use. Among nPEP users, those aged 25-49 years [hazard ratio (HR) = 1.3, 95% confidence interval (CI): 1.1 to 1.7], with more nPEP episodes (HR = 1.4, 95% CI: 1.3 to 1.5), who reported chemsex (HR = 1.3, 95% CI: 1.1 to 1.7), with a sexually transmitted infection history (HR = 1.5; 95% CI: 1.3 to 1.7), and who returned for their first nPEP follow-up visit (HR = 3.4, 95% CI: 2.7 to 4.2) had higher rates of PrEP linkage. There was no difference in PrEP persistence between nPEP-to-PrEP and PrEP only participants. CONCLUSION: Over one-third of nPEP users were subsequently prescribed PrEP. However, the large proportion of men who repeatedly use nPEP calls for more efficient PrEP-linkage services and, among those who use PrEP, improved persistence should be encouraged.

Impact of previous HIV resistance and virologic failures on virologic outcome following a switch to dolutegravir with 2 NRTIs among people living with HIV.

There is uncertainty regarding the potential virologic outcome associated with a change in antiretroviral therapy (ARV) among PLHIV who had previous documented virologic failure or who have been exposure to mono/dual nucleoside reverse transcriptase inhibitors (NRTI) therapy. The objective was to measure the potential impact of exposure to previous virologic failure or mono/dual NRTI regimen on virologic outcome of PLHIV following a switch to dolutegravir with 2 NRTIs from a viremia suppressive ARV therapy.Data from the Quebec HIV Cohort including 10219 PLHIV were collected through routine clinical care at 4 clinical sites in Montreal, Canada. This study includes patients whose ARV therapy was switched to dolutegravir with 2 NRTIs since 2013 with undetectable viral load for ≥6 months before switch. The association between exposure and post-switch virologic outcome was measured by marginal hazard ratio estimated using the Inverse probability weighting Cox model.Among the 1199 eligible PLHIV, 478 (39.9%) previously experienced at least one virologic failure or were exposed to mono/dual therapy before dolutegravir switch. Post-switch virologic failure after 30 months occurred in 4.1% (95% CI 2.1-7.9) of exposed compared to 4.1% (95% CI 2.3-7.4) in unexposed participants. The adjusted hazard ratio for the association between exposure and post-switch virologic failure was 0.84 (95% CI 0.35-2.01).Our findings suggest that switch to dolutegravir with 2 NRTIs from a suppressive therapy is a safe option for PLHIV with documented virologic failure and/or previous exposure to mono/dual NRTI therapy.

Treatment Switch to Dolutegravir With 2 Nucleoside Reverse-Transcriptase Inhibitors (NRTI) in Comparison to Continuation With Protease Inhibitor/Ritonavir Among Patients With Human Immunodeficiency Virus at Risk for Prior NRTI Resistance: A Cohort Analysis of Real-World Data.

BACKGROUND: Switching antiretroviral regimens when human immunodeficiency virus (HIV) viremia is controlled for a new regimen is challenging when there is the potential for prior nucleoside reverse-transcriptase inhibitor (NRTI) resistance. The objective was to study virologic outcomes after switching to dolutegravir compared with remaining on a boosted protease inhibitor (protease inhibitor/ritonavir [PI/r]) regimen in people with HIV (PWH) with prior documented virologic failure and/or exposure to mono/dual NRTIs. METHODS: We used the Quebec HIV Cohort including 10 219 PWH whose data were collected at 4 sites in Montreal, Canada. We included all PWH with documented virologic failure or exposure to mono/dual NRTI therapy who were virologically suppressed on a PI/r-based regimen for at least 6 months on or after January 1, 2014 (n = 532). A marginal structural Cox model analysis was used to estimate the effect of the switch to dolutegravir on virologic outcome compared with remaining on PI/r. The outcome was defined as 2 consecutive viral loads (VLs) >50 copies/mL or 1 VL >50 copies/mL if it occurred at the last VL available. RESULTS: Among 532 eligible participants, 216 (40.6%) had their regimen switched to dolutegravir with 2 NRTIs, whereas 316 (59.4%) remained on the PI/r with 2 NRTIs. The weighted hazard ratio for the effect of dolutegravir switch on virologic failure compared with patients whose regimen remained on PI/r was 0.57 (95% confidence interval, 0.21-1.52). CONCLUSIONS: We did not find evidence of an increased risk for virologic failure after switching to dolutegravir from PI/r among patients with previous virologic failure or prior exposure to mono/dual NRTI.

Improving the reporting of cancer-specific mortality and survival in research using cancer registry data.

Population-based registries are increasingly used in cancer research. In such studies, cancer-specific mortality or survival is frequently used as the primary outcome. To determine whether a putative cancer was part of the causal chain of events leading to death, cancer registries primarily rely on death certificates. Hence, they depend on the subjective interpretation of information available to medical examiners at the time of death. Misclassification may occur: studies report misclassification of cancer as a cause of death in 15%-35% of death certificates based on evaluation by expert panels and/or autopsy reports. Further misclassification may occur when coding death causes in the cancer registry. Researchers should be aware of potential misclassification bias when using cancer registry data. Differential misclassification may bias the results towards or away from the null hypothesis, depending on whether there is relative over- or under-reporting of cancer-related deaths in one group. Strategies to improve reporting of cancer-specific survival/mortality include (1) describing the procedure used to identify cancer-specific deaths; (2) considering the use of multiple definitions of cancer-related deaths (strict/liberal definitions of cancer-specific deaths, and/or addition of relative survival as an outcome); and (3) reporting cancer-specific survival/mortality together with the objectively measured parameters overall survival or all-cause mortality.

Cohort profile: l'Actuel Pre-Exposure Prophylaxis (PrEP) Cohort study in Montreal, Canada.

PURPOSE: The l'Actuel PrEP Cohort was established to monitor the uptake, effectiveness, safety and changes in sexual risk behaviours among individuals receiving pre-exposure prophylaxis (PrEP) for the prevention of HIV. This prospective dynamic cohort is based at Clinique médicale l'Actuel, a large sexual health clinic located in Montreal, Canada. PARTICIPANTS: Since the cohort inception in January of 2013 through June 2018, 2156 individuals consulted for PrEP as participants in the l'Actuel PrEP Cohort. Median age was 35 years (IQR: 29-44 years) and the majority (96%) were men who have sex with men. Among 1551 individuals who initiated PrEP care, the median duration of follow-up was 9.2 months (IQR: 3.7-19.6), with substantial variation based on year of cohort entry. The l'Actuel PrEP Cohort contains both daily and intermittent 'on-demand' PrEP users and has the largest reported population of intermittent PrEP users (n=406) in North America. FINDINGS TO DATE: No incident HIV infections have occurred among individuals using PrEP over 1637 person-years of follow-up. However, retention in PrEP care is essential as three individuals who discontinued PrEP subsequently acquired HIV, translating to an HIV incidence of 3.9 cases per 100 person-years (95% CI: 1.3 to 12.1). Among a sample of participants with 1 year of follow-up before and after PrEP initiation (n=109), a moderate increase in sexually transmitted infections was observed following PrEP start. FUTURE PLANS: The l'Actuel PrEP Cohort continues to grow with new participants starting PrEP monthly and extended follow-up for existing users. The cohort data will be used for ongoing monitoring of PrEP and for population-level modelling of the impact of PrEP on HIV incidence in Montreal.