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Abstract Background Scholars recommend providing migrants living with HIV (MLWH) with free treatment, rapidly, once linked to care to optimize their HIV-related experiences and health outcomes. Quantitative evaluations of patient-reported measures for MLWH in such models are necessary to explore the viability of these recommendations. Methods Within a 96-week prospective cohort study at a multidisciplinary HIV clinic, participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for free and rapidly following care linkage. Eight patient-reported measures were administered at weeks 4, 24, and 48: (1) mMOS-SS to measure perceived social support; (2) IA-RSS to measure internalized stigma; (3) K6 to measure psychological distress; (4) PROMIS to measure self-efficacy with treatment taking; (5) G-MISS to measure perceived compliance with clinicians’ treatment plans; (6) HIVTSQ to measure treatment satisfaction; (7) CARE to measure perceived provider empathy; and (8) PRPCC to measure perceived clinician cultural competence. Linear mixed modelling with bootstrapping was conducted to identify significant differences by sociodemographics and time. Results Across weeks 4, 24, and 48, results suggest that MLWH enrolled in this study experienced moderate levels of social support; elevated levels of HIV-related stigma; moderate levels of distress; high self-efficacy with daily medication self-management; great compliance with clinicians’ treatment plans; high treatment satisfaction; high perceived empathy; and high perceived cultural competence. Experience of social support (i.e., mMOS-SS scores) differed significantly by birth region. Experience of HIV-related stigma (i.e., IA-RSS scores) differed significantly by birth region, age, and language. Experience of distress (i.e., K6 scores) differed significantly by sexual orientation. Experience of treatment satisfaction (i.e., HIVTSQ scores) differed significantly by birth region and age. No significant differences were identified by time for any measure. Conclusion Overall, participants expressed positive experiences around treatment and care, alongside comparably lower perceptions of social support, internalized stigma, and distress, potentially underscoring a need to embed targeted, well-funded, and accessible mental health support within HIV care models.

BackgroundLittle is known about the impact of the COVID-19 pandemic on hepatitis C (HCV) screening efforts in carceral settings. We explored the impact of the pandemic on HCV screening in two of Quebec’s largest provincial prisons.MethodsRetrospective data of HCV-related laboratory tests between July 2018 and February 2022 at l’Établissement de détention de Montréal (EDM) and l’Établissement de détention de Rivière-des-Prairies (EDRDP) were obtained. To examine the association between the pandemic and the number of HCV-antibody (HCV-Ab) tests, a three-level time period variable was created: pre-outbreak, outbreak, and post-outbreak. Negative binomial regression (with monthly admissions as an offset) was used to assess the change in HCV-Ab tests across time periods and by prisons. Adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) were calculated.ResultsA total of 1,790 HCV-Ab tests were performed; 56 (3%) were positive. Among these, 44 (79%) HCV RNA tests were performed; 23 (52%) were positive. There was a significant decrease in HCV-Ab screening at EDM during the outbreak (aOR 0.29; 95% CI 0.17–0.48) and post-outbreak (aOR 0.49; 95% CI 0.35–0.69) periods, compared to the pre-outbreak period. There was no significant change in HCV-Ab screening at EDRDP during the outbreak (aOR 0.98; 95% CI 0.49–2.11) but a significant increase in HCV-Ab screening post-outbreak (aOR 1.66; 95% CI 1.04–2.72).ConclusionThe COVID-19 pandemic negatively affected HCV screening at EDM but had minimal impact at EDRDP. To eliminate HCV from carceral settings, minimizing screening interruptions during future outbreaks and combined HCV/SARS-CoV-2 screening should be prioritized.

Summary: Background: People who inject drugs (PWID) are a priority population in HCV elimination programming. Overcoming sex and gender disparities in HCV risk, prevention, and the cascade of care is likely to be important to achieving this goal, but these have not yet been comprehensively reviewed. Methods: Systematic review and meta-analysis. We searched Pubmed, EMBASE and the Cochrane Database of Systematic Reviews 1 January 2012–22 January 2024 for studies of any design reporting sex or gender differences among PWID in at least one of: sharing of needles and/or syringes, incarceration history, injection while incarcerated, participation in opioid agonist treatment or needle and syringe programs, HCV testing, spontaneous HCV clearance, direct-acting antiviral (DAA) treatment initiation or completion, and sustained virological response (SVR). Assessment of study quality was based on selected aspects of study design. Additional data were requested from study authors. Data were extracted in duplicate and meta-analysed using random effects models. PROSPERO registration CRD42022342806. Findings: 9533 studies were identified and 92 studies were included. Compared to men, women were at greater risk for receptive needle and syringe sharing (past 6–12 months: risk ratio (RR) 1.12; 95% confidence interval (CI) 1.01–1.23;

IntroductionCorrectional facilities are high-priority settings for coordinated public health responses to the COVID-19 pandemic. These facilities are at high risk of disease transmission due to close contacts between people in prison and with the wider community. People in prison are also vulnerable to severe disease given their high burden of co-morbidities.MethodsWe developed a mathematical model to evaluate the effect of various public health interventions, including vaccination, on the mitigation of COVID-19 outbreaks, applying it to prisons in Australia and Canada.ResultsWe found that, in the absence of any intervention, an outbreak would occur and infect almost 100% of people in prison within 20 days of the index case. However, the rapid rollout of vaccines with other non-pharmaceutical interventions would almost eliminate the risk of an outbreak.DiscussionOur study highlights that high vaccination coverage is required for variants with high transmission probability to completely mitigate the outbreak risk in prisons.

Introduction Advanced chronic liver disease (ACLD) is a major cause of death for people with HIV (PWH). While viral hepatitis coinfections are largely responsible for this trend, metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging concern for PWH. We aimed to assess the contribution of MASLD to incident ACLD in PWH.Methods and analysis This multicentre prospective observational cohort study will enrol 968 consecutive HIV monoinfected patients from four Canadian sites, excluding subjects with alcohol abuse, liver disease other than MASLD, or ACLD at baseline. Participants will be followed annually for 4 years by clinical evaluation, questionnaires, laboratory testing and Fibroscan to measure liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). The primary outcome will be incidence of ACLD, defined as LSM>10 kPa, by MASLD status, defined as CAP≥285 dB/m with at least one metabolic abnormality, and to develop a score to classify PWH according to their risk of ACLD. Secondary outcomes will include health-related quality of life (HRQoL) and healthcare resource usage. Kaplan-Meier survival method and Cox proportional hazards regression will calculate the incidence and predictors of ACLD, respectively. Propensity score methods and marginal structural models will account for time-varying exposures. We will split the cohort into a training set (to develop the risk score) and a validation set (for validation of the score). HRQoL scores and healthcare resource usage will be compared by MASLD status using generalised linear mixed effects model.Ethics and dissemination This protocol has been approved by the ethics committees of all participating institutions. Written informed consent will be obtained from all study participants. The results of this study will be shared through scientific publications and public presentations to advocate for the inclusion of PWH in clinical trials of MASLD-targeted therapies and case-finding of ACLD in PWH.

Background: Epidemics of COVID-19 strained hospital resources. We describe temporal trends in mortality risk and length of stays in hospital and intensive care units (ICUs) among patients with COVID-19 hospitalized through the first three epidemic waves in Canada. Methods: We used population-based provincial hospitalization data from the epicenters of Canada's epidemics (Ontario and Québec). Adjusted estimates were obtained using marginal standardization of logistic regression models, accounting for patient-level and hospital-level determinants. Results: Using all hospitalizations from Ontario (N = 26,538) and Québec (N = 23,857), we found that unadjusted in-hospital mortality risks peaked at 31% in the first wave and was lowest at the end of the third wave at 6–7%. This general trend remained after adjustments. The odds of in-hospital mortality in the highest patient load quintile were 1.2-fold (95% CI: 1.0–1.4; Ontario) and 1.6-fold (95% CI: 1.3–1.9; Québec) that of the lowest quintile. Mean hospital and ICU length of stays decreased over time but ICU stays were consistently higher in Ontario than Québec. Conclusions: In-hospital mortality risks and length of ICU stays declined over time despite changing patient demographics. Continuous population-based monitoring of patient outcomes in an evolving epidemic is necessary for health system preparedness and response.

Introduction Chronic cytomegalovirus (CMV) infection is very frequent in people living with HIV (PLWH). High anti-CMV IgG titres, which may be linked to transient CMV replication, have been associated with earlier mortality, CD8 T-cell expansion, lower CD4/CD8 ratio and increased T-cell senescence. We previously showed that anti-CMV IgG titres correlated with gut permeability in PLWH on antiretroviral therapy (ART), which was associated with microbial translocation, systemic inflammation and non-infectious/non-AIDS comorbidities. Letermovir, a novel anti-CMV drug with a good safety profile, was recently approved for anti-CMV prophylaxis in allogeneic haematopoietic stem cell transplant recipients. A drastic and selective reduction of both low-grade replication and clinically significant CMV infections, combined with an improved immune reconstitution have been reported. In vitro, letermovir prevented CMV-induced epithelial disruption in intestinal tissues. Based on these findings, we aim to assess whether letermovir could inhibit CMV subclinical replication in CMV-seropositive PLWH receiving ART and, in turn, decrease CMV-associated gut damage and inflammation.Method and analysis We will conduct a multi-centre, open-label, randomised, controlled clinical trial, including a total of 60 CMV-seropositive ART-treated PLWH for at least 3 years, with a viral load 400 cells/µL. Forty participants will be randomised to receive letermovir for 14 weeks and 20 participants will receive standard of care (ART) alone. Plasma, pheripheral blood mononuclear cells (PBMCs), and stool samples will be collected. Colon biopsies will be collected in an optional substudy. We will assess the effect of letermovir on gut damage, microbial translocation, inflammation and HIV reservoir size.Ethics and dissemination The study was approved by Health Canada and the Research Ethics Boards of the McGill University Health Centre (MUHC-REB, protocol number: MP37-2022-8295). Results will be made available through publications in open access peer-reviewed journals and through the CIHR/CTN website.Trial registration number NCT05362916.

BackgroundCorrectional workers are at increased risk of SARS-CoV-2 infection. We examined the seroprevalence of SARS-CoV-2, determined the effects of carceral and occupational exposures on seropositivity, and explored predictors of COVID-19 vaccine uptake among correctional workers in Quebec, Canada.MethodsWe conducted a cross-sectional seroprevalence study in three provincial prisons. The primary and secondary outcomes were SARS-CoV-2 antibody seropositivity (Roche Elecsys® serology test) and self-reported COVID-19 vaccination status (“fully vaccinated” defined as two doses or prior infection plus one dose), respectively. Poisson regression models with robust standard error were used to examine the effect of occupational variables with SARS-CoV-2 seropositivity and predictors of COVID-19 vaccine uptake. Estimates are presented as crude and adjusted prevalence ratios (aPR) with 95% confidence intervals (95% CI).ResultsFrom 14 July to 15 November 2021, 105/600 (18%) correctional workers tested positive across three prisons (range 11–21%); 76% were fully vaccinated. Seropositivity was affected by prison occupation (aPR 1.59, 95% CI 1.11–2.27 for correctional officers vs. all other occupations) and low perceived concern of SARS-CoV-2 acquisition (aPR 1.62, 95% CI 1.11–2.38 for not/hardly worried vs. somewhat/extremely worried). Predictors of being fully vaccinated included race/ethnicity (aPR 0.86, 95% CI 0.76–0.99 for visible minority vs. White), presence of comorbidities (aPR 1.14, 95% CI 1.02–1.28 for > 2 vs. none), and prison occupation (aPR 0.82, 95% CI 0.73–0.92 for correctional officers vs. all other occupations).ConclusionsCorrectional officers were most likely to have acquired SARS-CoV-2, but least likely to be vaccinated, underscoring the importance of addressing both occupational risks and COVID-19 vaccine hesitancy to mitigate future outbreaks.

BackgroundPeople with COVID-19 are instructed to self-isolate at home. During self-isolation, they may experience anxiety and insufficient care. Patient portals can allow patients to self-monitor and remotely share their health status with health care professionals, but little data are available on their feasibility. ObjectiveThis paper presents the protocol of the Opal-COVID Study. Its objectives are to assess the implementation of the Opal patient portal for distance monitoring of self-isolating patients with COVID-19, identify influences on the intervention’s implementation, and describe service and patient outcomes of this intervention. MethodsThis mixed methods pilot study aims to recruit 50 patient participants with COVID-19 tested at the McGill University Health Centre (Montreal, Canada) for 14 days of follow-up. With access to an existing patient portal through a smartphone app, patients will complete a daily self-assessment of symptoms, vital signs, and mental health monitored by a nurse, and receive teleconsultations as needed. Study questionnaires will be administered to collect data on sociodemographic characteristics, medical background, implementation outcomes (acceptability, usability, and respondent burden), and patient satisfaction. Coordinator logbook entries will inform on feasibility outcomes, namely, on recruitment, retention, and fidelity, as well as on the frequency and nature of contacts with health care professionals. The statistical analyses for objectives 1 (implementation outcomes), 3 (service outcomes), and 4 (patient outcomes) will evaluate the effects of time and sociodemographic characteristics on the outcomes. For objectives 1 (implementation outcomes) and 4 (patient outcomes), the statistical analyses will also examine the attainment of predefined success thresholds. As for the qualitative analyses, for objective 2 (influences on implementation), semistructured qualitative interviews will be conducted with 4 groups of stakeholders (ie, patient participants, health care professionals, technology developers, and study administrators) and submitted for content analysis, guided by the Consolidated Framework for Implementation Research to help identify barriers to and facilitators of implementation. For objective 3 (service outcomes), reasons for contacting health care professionals through Opal will also be submitted for content analysis. ResultsBetween December 2020 and March 2021, a total of 51 patient participants were recruited. Qualitative interviews were conducted with 39 stakeholders from April to September 2021. Delays were experienced owing to measures taken at the McGill University Health Centre to address COVID-19. The quantitative and qualitative analyses began in May 2022. As of June 2022, a total of 2 manuscripts (on the implementation and the patient outcomes) were being prepared, and 3 conference presentations had been given on the study’s methods. ConclusionsThis protocol is designed to generate multidisciplinary knowledge on the implementation of a patient portal–based COVID-19 care intervention and will lead to a comprehensive understanding of feasibility, stakeholder experience, and influences on implementation that may prove useful for scaling up similar interventions. Trial RegistrationClinicalTrials.gov NCT04978233; https://clinicaltrials.gov/ct2/show/NCT04978233 International Registered Report Identifier (IRRID)DERR1-10.2196/35760

Introduction: Canadian correctional institutions have been prioritized for COVID-19 vaccination given the multiple outbreaks that have occurred since the start of the pandemic. Given historically low vaccine uptake, we aimed to explore barriers and facilitators to COVID-19 vaccination acceptability among people incarcerated in federal prisons. Methods: Three federal prisons in Quebec, Ontario, and British Columbia (Canada) were chosen based on previously low influenza vaccine uptake among those incarcerated. Using a qualitative design, semi-structured interviews were conducted with a diverse sample (gender, age, and ethnicity) of incarcerated people. An inductive-deductive analysis of audio-recorded interview transcripts was conducted to identify and categorize barriers and facilitators within the Theoretical Domains Framework (TDF). Results: From March 22–29, 2021, a total of 15 participants (n = 5 per site; n = 5 women; median age = 43 years) were interviewed, including five First Nations people and six people from other minority groups. Eleven (73%) expressed a desire to receive a COVID-19 vaccine, including two who previously refused influenza vaccination. We identified five thematic barriers across three TDF domains: social influences (receiving strict recommendations, believing in conspiracies to harm), beliefs about consequences (believing that infection control measures will not be fully lifted, concerns with vaccine-related side effects), and knowledge (lack of vaccine-specific information), and eight thematic facilitators across five TDF domains: environmental context and resources (perceiving correctional employees as sources of outbreaks, perceiving challenges to prevention measures), social influences (receiving recommendations from trusted individuals), beliefs about consequences (seeking individual and collective protection, believing in a collective “return to normal”, believing in individual privileges), knowledge (reassurance about vaccine outcomes), and emotions (having experienced COVID-19-related stress). Conclusions: Lack of information and misinformation were important barriers to COVID-19 vaccine acceptability among people incarcerated in Canadian federal prisons. This suggests that educational interventions, delivered by trusted health care providers, may improve COVID-19 vaccine uptake going forward.

Abstract Background At the McGill University Health Centre (MUHC), 10% of patients living with HIV do not return for care annually. Currently, no formal system exists to re-engage out-of-care (OOC) patients. Lost & Found, developed using an implementation science approach, is an intervention to re-engage OOC patients. It is based on existing evidence-based interventions and will be adapted for use by nurses at the MUHC. The aims of this study are to simultaneously assess both implementation and effectiveness of Lost & Found in order to determine the viability of a future multisite stepped-wedge cluster randomised trial. Methods Lost & Found consists of two core elements: identifying and contacting OOC patients. Based on formative work involving MUHC nurses, and the use of a combined implementation framework (enhanced Replicating Effective Programs, Tailored Implementation for Chronic Diseases, and Proctor et al.’s implementation outcomes), we will adapt the intervention to our clinic. Adaptations include the creation of an OOC risk prediction tool, an automated real-time OOC list, and prioritization of high-risk OOC patients for re-engagement. Delivery and ongoing adaptation of the intervention will follow a three-pronged implementation strategy consisting of (1) promoting adaptability; (2) planning, engaging, executing, evaluating, and reflecting cycles; and (3) internal facilitation. This 15-month quasi-experimental pilot study adopts a type II implementation-effectiveness hybrid design. To evaluate implementation, a convergent parallel mixed-methods approach will guide the mixing of qualitative and quantitative data at time points throughout the study. In addition, descriptive and pre-post analyses, for each of the implementation and sustainability phases, will inform evaluations of the cumulative effectiveness and sustainability of the Lost & Found intervention. Discussion This study will provide preliminary evidence for (1) the utility of our chosen implementation strategies and (2) the effectiveness of the intervention. Ultimately, this information may be used to inform future re-engagement efforts using implementation science in other HIV care centres. In addition, the procedures and measurement tools developed for this study will be foundational to the development of a multi-site, randomised stepped wedge study that would provide more robust evidence in support of the Lost & Found intervention.

Background Vaccine uptake rates have been historically low in correctional settings. To better understand vaccine hesitancy in these high-risk settings, we explored reasons for COVID-19 vaccine refusal among people in federal prisons. Methods Three maximum security all-male federal prisons in British Columbia, Alberta, and Ontario (Canada) were chosen, representing prisons with the highest proportions of COVID-19 vaccine refusal. Using a qualitative descriptive design and purposive sampling, individual semi-structured interviews were conducted with incarcerated people who had previously refused at least one COVID-19 vaccine until data saturation was achieved. An inductive–deductive thematic analysis of audio-recorded interview transcripts was conducted using the Conceptual Model of Vaccine Hesitancy. Results Between May 19-July 8, 2021, 14 participants were interviewed (median age: 30 years; n = 7 Indigenous, n = 4 visible minority, n = 3 White). Individual-, interpersonal-, and system-level factors were identified. Three were particularly relevant to the correctional setting: 1) Risk perception: participants perceived that they were at lower risk of COVID-19 due to restricted visits and interactions; 2) Health care services in prison: participants reported feeling “punished” and stigmatized due to strict COVID-19 restrictions, and failed to identify personal benefits of vaccination due to the lack of incentives; 3) Universal distrust: participants expressed distrust in prison employees, including health care providers. Interpretation Reasons for vaccine refusal among people in prison are multifaceted. Educational interventions could seek to address COVID-19 risk misconceptions in prison settings. However, impact may be limited if trust is not fostered and if incentives are not considered in vaccine promotion.

Hepatitis C virus (HCV) infection represents the major cause of chronic liver disease, leading to a wide range of hepatic diseases, including cirrhosis and hepatocellular carcinoma. It is the leading indication for liver transplantation worldwide. In addition, there is a growing body of evidence concerning the role of HCV in extrahepatic manifestations, including immune-related disorders and metabolic abnormalities, such as insulin resistance and steatosis. HCV depends on its host cells to propagate successfully, and every aspect of the HCV life cycle is closely related to human lipid metabolism. The virus circulates as a lipid-rich particle, entering the hepatocyte via lipoprotein cell receptors. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation (steatosis) and circulating hypocholesterolemia. Patients with chronic HCV are at increased risk for hepatic steatosis, dyslipidemia, and cardiovascular disease, including accelerated atherosclerosis. This review aims to describe different aspects of the HCV viral life cycle as it impacts host lipoproteins and lipid metabolism. It then discusses the mechanisms of HCV-related hepatic steatosis, hypocholesterolemia, and accelerated atherosclerosis.

Abstract Background Migrants represent an increasing proportion of people living with HIV in many developed countries. We aimed to describe the HIV care cascade and baseline genotypic resistance for newly diagnosed asylum seekers referred to the McGill University Health Centre (MUHC) in Montreal, Quebec, Canada. Methods We conducted a retrospective cohort study of patients linked to the MUHC from June 1, 2017 to October 31, 2018. We calculated the median time (days; interquartile range (IQR)) from: 1) entry into Canada to immigration medical examination (IME) (i.e. HIV screening); 2) IME to patient notification of diagnosis; 3) notification to linkage to HIV care (defined as a CD4 or viral load (VL) measure); 4) linkage to HIV care to combination antiretroviral therapy (cART) prescription; and 5) cART prescription to viral suppression (defined as a VL 1 antiretroviral. Results Overall, 43% (60/139) of asylum seekers were newly diagnosed in Canada. Among these, 62% were late presenters (CD4 100,000 copies/ml). Median time from entry to IME: 27 days [IQR:13;55]; IME to notification: 28 days [IQR:21;49]; notification to linkage: 6 days [IQR:2;19]; linkage to cART prescription: 11 days [IQR:6;17]; and cART to viral suppression: 42 days [IQR:31;88]; 45% were linked to HIV care within 30 days. One-fifth (21%) had baseline resistance to at least one antiretroviral agent; the K103 N/S mutation was the most common mutation. Conclusions While the majority of newly diagnosed asylum seekers were late presenters, only 45% were linked to care within 30 days. Once linked, care and viral suppression were rapid. Delays in screening and linkage to care present increased risk for onward transmission, and in the context of 21% baseline resistance, consideration of point-of-care testing and immediate referral at IME screening should be made.

Abstract Objectives The aim of the RAAS-COVID-19 randomized control trial is to evaluate whether an upfront strategy of temporary discontinuation of renin angiotensin aldosterone system (RAAS) inhibition versus continuation of RAAS inhibition among patients admitted with established COVID-19 infection has an impact on short term clinical and biomarker outcomes. We hypothesize that continuation of RAAS inhibition will be superior to temporary discontinuation with regards to the primary endpoint of a global rank sum score. The global rank sum score has been successfully used in previous cardiovascular clinical trials. Trial design This is an open label parallel two arm (1,1 ratio) randomized control superiority trial of approximately 40 COVID-19 patients who are on chronic RAAS inhibitor therapy. Participants Adults who are admitted to hospital within the McGill University Health Centre systems (MUHC) including Royal Victoria Hospital (RVH), Montreal General Hospital (MGH) and Jewish General Hospital (JGH) and who are within 96 hours of COVID-19 diagnosis (confirmed via PCR on any biological sample) will be considered for the trial. Of note, the initial protocol to screen and enrol within 48 hours of COVID-19 diagnosis was extended through an amendment, to 96 hours to increase feasibility. Participants have to be 18 years or older and would have to be on RAAS inhibitors for at least a month to be considered eligible for the study. Additionally, RAAS inhibitors should not have been held for more than 48 hours before randomization. A list of inclusion and exclusion criteria can be found in the full protocol document. In order to prevent heart failure exacerbation, patients with reduced ejection fraction were excluded from the trial. Once a patient is admitted on the ward with a diagnosis of COVID-19, we will confirm with the treating physician if the participant is suitable for the RAAS-COVID trial and meets all the inclusion and exclusion criteria. If the patient is eligible and informed consent has been obtained we will collect data on sex, age, ethnicity, past medical history and list of medications (e.g. other anti-hypertensives or anticoagulants), for further analysis. Intervention and comparator All the study participants will be randomized to a strategy of temporarily holding the RAAS inhibitor [intervention] versus continuing the RAAS inhibitor [continued standard of care]. Among participants who are randomized to the intervention arm, alternative guide-line directed anti-hypertensive medication will be provided to the treating physician team (detail in study protocol). In the intervention arm RAAS inhibitor will be withheld for a total of 7 days with the possibility of the withdrawn medication being initiated at any point after day 7 or on the day of discharge. The recommendation for re-initiating the withdrawn medication will be made to the treating physician. The re-initiation of these therapies are according to standard convention and follow-up as per Canadian guidelines. Additionally, the date of restarting the withdrawn medication or whether the medication was re-prescribed on discharge or not, will be collected. This will be used to conduct a sensitivity analysis. Furthermore, biomarkers such as troponin, c-reactive protein (CRP) and lymphocyte count will be assessed during the same time period. Samples will be collected on randomization, day 4 and day 7. Main outcomes Primary endpoint In this study the primary end point is a global rank score calculated for all participants, regardless of treatment assignment ( score from 0 to 7). Please refer to table 4 in the full protocol. In the context of the current trial, it is estimated that death is the most meaningful endpoint, and therefore has the highest score ( score of 7). This is followed by admission to ICU, the need for mechanical ventilation etc. The lowest scores ( score of 1) are assigned to biomarker changes (e.g. change in troponin, change in CRP). This strategy has been used successfully in cardiovascular disease trials and therefore is applicable to the current trial. The primary endpoint for the present trial is assessed from baseline to day 7 (or discharge). Participants are ranked across the clinical and biomarker domains. Lower values indicate better health (or stability). Participants who died during the 7th day of the study will be ranked based on all events occurring before their death and also including the fatal event in the score. Next, participants who did not die but were transferred to ICU for invasive ventilation will be ranked based on all the events occurring before the ICU entry and also including the ICU admission in the score. Those participants who did not die were not transferred to ICU for invasive ventilation, will be ranked based on the subsequent outcomes. The mean rank score will then be compared between groups. In this scheme, a lower mean rank score indicates greater overall stability for participants. Secondary endpoints : The key secondary endpoints are the individual components of the primary components and include the following: death, transfer to ICU primarily for invasive ventilation, transfer to ICU for other indication, non-fatal MACE ( any of following, MI, stroke, acute HF, new onset Afib), length of stay > 4 days, development of acute kidney injury ( > 40% decline in eGFR or doubling of serum creatinine), urgent intravenous treatment for high blood pressure, 30% increase in baseline high sensitivity troponin, 30% increase in baseline BNP, increase in CRP to > 30% in 48 hours and lymphocyte count drop> 30%. We will also look at the World Health Organization (WHO) ordinal scale for clinical improvement (in COVID-19) in our data. In this scale death will be assigned the highest score of 8. Patients with no limitation of activity will be assigned a score of 1 which indicates overall more stability (3). Additionally, we will evaluate the potential effects of discontinuing RAAS inhibition on alternative schedules (longer/shorter than 7 days, intermittent discontinuation) using a mechanistic mathematical model of COVID-19 immunopathology calibrated to data collected from our patient cohort. In particular, we will assess the impact of alternative schedules on primary and secondary endpoints including increases to baseline CRP and lymphocyte counts. Randomization Participants will be randomized in a 1:1 ratio. Randomization will be performed within an electronic database system at the time of enrolment using a random number generator, an approach that has been successfully used in other clinical trials. Neither participant, study team, or treating team will be blinded to the intervention arm. Blinding This is an open label study with no blinding. Numbers to be randomised (sample size) The approximate number of participants required for this trial is 40 patients (randomized 1:1 to continuation versus discontinuation of RAAS inhibitors). This number was calculated based on previous rates of outcomes for COVID-19 in the literature (e.g. death, ICU transfer) and statistical power calculations. Trial Status Protocol number: MP-37-2021-6641, Version 4: 01-10-2020. Trial start date September 1st 2020 and currently enrolling participants. Estimated end date for recruitment of participants : July 2021. Estimated end date for study completion: September 1st 2021. Trial registration Trial registration: ClincalTrials.gov : NCT04508985 , date of registration: August 11th , 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Background: Fat alterations are frequent in people with HIV (PWH) and predict worse cardiometabolic outcomes. Visceral adipose tissue (VAT) is associated with ectopic fat accumulation in the liver. We aimed to investigate nonalcoholic fatty liver disease (NAFLD) diagnosed by controlled attenuation parameter (CAP) as a potential marker of visceral adiposity in PWH. Methods: We conducted a prospective pilot study of HIV mono-infected patients undergoing metabolic characterization and paired CAP measured by transient elastography with dual-energy X-ray absorptiometry (DEXA) scan. NAFLD was defined as CAP ≥ 285 dB/m, in absence of alcohol abuse. Excess visceral adiposity was defined as VAT > 1.32 Kg. Pairwise correlation, area under the curve (AUC) and logistic regression analysis were employed to study the association between VAT and CAP. Results: Thirty patients were included, of whom 50% had NAFLD. CAP was correlated with VAT (r = 0.650, p < 0.001) measured by DEXA scan. After adjusting for duration of HIV infection, body mass index and waist circumference, CAP remained the only independent predictor of excess VAT (adjusted odds ratio 1.05, 95% confidence interval [CI] 1.01–1.10). The AUC analysis determined CAP had excellent performance to diagnose excess VAT (AUC 0.92, 95% CI 0.81–1.00), higher than BMI and waist circumference. The optimized CAP cut-off to diagnose excess VAT was 266 dB/m, with a sensitivity of 88.3% and a specificity of 84.6%. Conclusions: NAFLD diagnosed by CAP is associated with VAT in PWH independently of anthropometric measures of obesity. CAP may be a potential diagnostic marker of visceral adiposity in the practice of HIV medicine.

Human herpesvirus-8 (HHV8)-associated multicentric Castleman disease (HHV8-MCD) is a rare nonmalignant lymphoproliferative disorder most commonly observed in PLWH. Herein, we describe an HIV-infected adult male from Cameroon with relapsing HHV8-MCD (HIV+MCD). The patient developed constitutional symptoms, diffuse lymphadenopathy, thrombocytopenia and autoimmune hemolytic anemia. Excisional lymph node biopsy findings were consistent with HHV8-MCD. He was successfully treated with corticosteroids and rituximab. One year later, he developed relapsing disease and was successfully treated again with rituximab. Interestingly, HIV viral load blips correlate with MCD flares, suggesting that low-level viremia is linked with T-cell clonal expansion and/or inflammation, rather than a lack of effective antiretroviral therapy. Rituximab either alone or in combination with chemotherapy for aggressive disease is the standard of care, with approximately 95% of treated patients achieving complete remission. Despite highly effective therapy, HIV+MCD often presents with a relapsing and remitting disease course and carries an increased risk for the development of HHV8-associated lymphoma.

Introduction In 2019, the United Nations signalled a substantial rise in the number of international migrants, up to 272 million globally, about half of which move to only 10 countries, including 8 member nations of the Organization for Economic Co-operation and Development (OECD). Migrants in OECD countries are often at higher risk for acquiring HIV and have a higher frequency of delayed HIV diagnosis. The barriers and facilitators that migrant people living with HIV (PLWH) in OECD countries face in relation to HIV care are insufficiently understood. The five-step HIV Care Cascade Continuum (HCCC) is an effective model to identify gaps, barriers and facilitators associated with HIV care. The purpose of this study is to generate a comprehensive, multilevel understanding of barriers and facilitators regarding the five steps of the HCCC model in OECD countries by migration status.Methods and analysis A systematic mixed studies review using a data-based convergent design will be conducted. Medline, Embase, Scopus, CINAHL and the Cochrane Library will be searched on 25 March 2020. Screening and critical appraisal will be conducted independently by the first author. Authors 3–5 will act as second reviewers, each independently conducting 33% of the screening and appraisal. Quantitative data will be transformed to qualitative data and be synthesised using thematic analysis. The Mixed Methods Appraisal Tool will be used for quality assessment. An advisory committee, composed of four migrant PLWH, will be involved in screening and appraising 5% of articles to build knowledge and experience with systematic reviews. They will also be involved in analysis and dissemination.Ethics and dissemination Ethics approval was obtained from the McGill University Health Centre (15-188-MUHC, 2016-1697, eReviews 4688). Publications arising from this study will be open-access.PROSPERO registration number CRD42020172122.

To improve health outcomes in people living with HIV, adoption of evidence-based interventions (EBIs) using effective and transferable implementation strategies to optimise the delivery of healthcare is needed. ViiV Healthcare's Positive Pathways initiative was established to support the UNAIDS 90-90-90 goals. A compendium of EBIs was developed to address gaps within the HIV care continuum, yet it was unknown whether efforts existed to adapt and implement these EBIs across diverse clinical contexts. Therefore, this review sought to report on the use of implementation science in adapting HIV continuum of care EBIs. A systematic literature review was undertaken to summarise the evaluation of implementation and effectiveness outcomes, and report on the use of implementation science in HIV care. Ten databases were reviewed to identify studies (time-period: 2013-2018; geographic scope: United States, United Kingdom, France, Germany, Italy, Spain, Canada, Australia and Europe; English only publications). Studies were included if they reported on people living with HIV or those at risk of acquiring HIV and used interventions consistent with the EBIs. A broad range of study designs and methods were searched, including hybrid designs. Overall, 118 publications covering 225 interventions consistent with the EBIs were identified. These interventions were evaluated on implementation (N = 183), effectiveness (N = 81), or both outcomes (N = 39). High variability in the methodological approaches was observed. Implementation outcomes were frequently evaluated but use of theoretical frameworks was limited (N = 13). Evaluations undertaken to assess effectiveness were inconsistent, resulting in a range of measures. This review revealed extensive reporting on implementation science as defined using evaluation outcomes. However, high variability was observed in how implementation outcomes and effectiveness were defined, quantified, and reported. A more specific and consistent approach to conducting and reporting on implementation science in HIV could facilitate achievement of UNAIDS 90-90-90 targets.

Migrants are at an increased risk of HIV acquisition. We aimed to use phylogenetics to characterize transmission clusters among newly-diagnosed asylum seekers and to understand the role of networks in local HIV transmission. Retrospective chart reviews of asylum seekers linked to HIV care between 1 June 2017 and 31 December 2018 at the McGill University Health Centre and the Jewish General Hospital in Montreal were performed. HIV-1 partial pol sequences were analyzed among study participants and individuals in the provincial genotyping database. Trees were reconstructed using MEGA10 neighbor-joining analysis. Clustering of linked viral sequences was based on a strong bootstrap support (>97%) and a short genetic distance (n = 7 males) formed part of eight clusters. Four clusters (two to three people) included only study participants (n = 9) and four clusters (two to three people) included four study participants clustered with six individuals from the provincial genotyping database. Six (75%) clusters were HIV subtype B. We identified the presence of HIV-1 phylogenetic clusters among asylum seekers and at a population-level. Our findings highlight the complementary role of cohort data and population-level genotypic surveillance to better characterize transmission clusters in Quebec.