Harm reduction and multidisciplinary consultations for gay, bisexual, and other men who have sex with men practising chemsex based in a French infectious disease unit: patients' characteristics and perceptions.

BACKGROUND: Chemsex, a type of sexualised drug use, is expanding among gay, bisexual, and other men who have sex with men (GBMSM), with physical and mental health risks. Health-seeking behaviours of GBMSM practising chemsex is not clear. METHODS: Harm reduction (HR) consultations for GBMSM engaging in chemsex and seeking comprehensive services including HR were offered in a Parisian infectious disease unit. From December 2021 to January 2022, HR consultation patients completed an online survey on their consumption, health, used services, and perspective on consultations. We generated descriptive statistics, and tested (χ 2 ) the relationship between reporting a specialised follow-up and perceived usefulness of intervention. RESULTS: Of 172 patients, a total of 96 GBMSM (55.2%) completed the survey. Most ever consumed substance was 3-methylmethcathinone (3MMC; 92/96; 95.8%). Before consultations, about half consumed at least once a week (50/96; 52%), most reported negative impacts of chemsex on their social (60/96, 62.5%), professional (56/96, 58.3%), intimate (53/96; 55.21%), or sexual life (52/96; 54.17%). Also, more than two-thirds (n =57; 69.38%) had received a follow-up in specialised services: one-third had been followed in addictology (28/96, 29.2%) and/or psychotherapy (32/96, 33.3%), and one-fourth (24/96, 25.0%) had used emergency services. After consultations, three-quarters perceived the intervention as useful (n =74; 77.08%); we found no significant relationship with receiving a specialised follow-up; and most were satisfied with professionals' listening (90/96; 93.8%), and reported reduced risks (80/96; 83.3%). DISCUSSION: Multidisciplinary HR, preventive, diagnostical, and therapeutic sexological and psychiatric interventions are greatly needed among GBMSM practising chemsex. HR interventions accessible in services already attended by GBMSM are a valuable option.

Adapting and Evaluating an AI-Based Chatbot Through Patient and Stakeholder Engagement to Provide Information for Different Health Conditions: Master Protocol for an Adaptive Platform Trial (the MARVIN Chatbots Study).

BACKGROUND: Artificial intelligence (AI)-based chatbots could help address some of the challenges patients face in acquiring information essential to their self-health management, including unreliable sources and overburdened health care professionals. Research to ensure the proper design, implementation, and uptake of chatbots is imperative. Inclusive digital health research and responsible AI integration into health care require active and sustained patient and stakeholder engagement, yet corresponding activities and guidance are limited for this purpose. OBJECTIVE: In response, this manuscript presents a master protocol for the development, testing, and implementation of a chatbot family in partnership with stakeholders. This protocol aims to help efficiently translate an initial chatbot intervention (MARVIN) to multiple health domains and populations. METHODS: The MARVIN chatbots study has an adaptive platform trial design consisting of multiple parallel individual chatbot substudies with four common objectives: (1) co-construct a tailored AI chatbot for a specific health care setting, (2) assess its usability with a small sample of participants, (3) measure implementation outcomes (usability, acceptability, appropriateness, adoption, and fidelity) within a large sample, and (4) evaluate the impact of patient and stakeholder partnerships on chatbot development. For objective 1, a needs assessment will be conducted within the setting, involving four 2-hour focus groups with 5 participants each. Then, a co-construction design committee will be formed with patient partners, health care professionals, and researchers who will participate in 6 workshops for chatbot development, testing, and improvement. For objective 2, a total of 30 participants will interact with the prototype for 3 weeks and assess its usability through a survey and 3 focus groups. Positive usability outcomes will lead to the initiation of objective 3, whereby the public will be able to access the chatbot for a 12-month real-world implementation study using web-based questionnaires to measure usability, acceptability, and appropriateness for 150 participants and meta-use data to inform adoption and fidelity. After each objective, for objective 4, focus groups will be conducted with the design committee to better understand their perspectives on the engagement process. RESULTS: From July 2022 to October 2023, this master protocol led to four substudies conducted at the McGill University Health Centre or the Centre hospitalier de l'Université de Montréal (both in Montreal, Quebec, Canada): (1) MARVIN for HIV (large-scale implementation expected in mid-2024), (2) MARVIN-Pharma for community pharmacists providing HIV care (usability study planned for mid-2024), (3) MARVINA for breast cancer, and (4) MARVIN-CHAMP for pediatric infectious conditions (both in preparation, with development to begin in early 2024). CONCLUSIONS: This master protocol offers an approach to chatbot development in partnership with patients and health care professionals that includes a comprehensive assessment of implementation outcomes. It also contributes to best practice recommendations for patient and stakeholder engagement in digital health research. TRIAL REGISTRATION: ClinicalTrials.gov NCT05789901; https://classic.clinicaltrials.gov/ct2/show/NCT05789901. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54668.

The paradoxes of telehealth platforms: what did we learn from the use of telehealth platforms?

This article is an overview and reflection of the findings of an evaluative study conducted on a program called "Techno-Covid Partnership" (TCP) implemented in April 2020 at the Centre Hospitalier de l'Université de Montréal (CHUM) in Montreal, Canada. In the context of the COVID-19 pandemic, the CHUM decided in April 2020 to implement telehealth, virtual care, and telemonitoring platforms and technologies to maintain access to care and reduce the risks of contamination and spread of COVID-19 as well as to protect users of health services and health professionals. Three technological platforms for telehealth and remote care and monitoring have been developed, implemented, and evaluated in real-time within the framework of the TCP program. A cross-sectional study was carried out in which a questionnaire was used and administered to users of telehealth platforms including patients and healthcare professionals. The methods and results of the study have been published previously published. In the completion of the two articles published in this context, in this paper, we briefly recall the context of the study and the method performed. The main focus of the paper is on presenting a critical overview and reflection on the major findings of our evaluation of the use of telehealth platforms from the point of view of patients and health professionals and discuss certain paradoxes i.e., the advantages, challenges, recommendations, and other perspectives that emerged in this study.

Conceptions of sexual health by gay men living with HIV in serodifferent couples in Montreal, Canada: results from a qualitative analysis.

BACKGROUND: Gay, bisexual, and other men (GBM) who have sex with men living with HIV in serodifferent couples (one partner living with HIV, the other HIV-negative) may encounter unique sexual health challenges. This study aimed to explore their definition of sexual health that could improve service provision. METHODS: We interviewed 10 gay-identified men living with HIV from 2017 to 2019 as part of CTNPT013, a study on the sexual health of HIV serodifferent GBM couples conducted at two HIV-specialised clinics in Montreal, Canada. Participants partook in semi-structured interviews on the meaning of sexual health. We performed a content analysis of interview transcripts, coding them according to the 10 dimensions of Robinson's Sexual Health Model. RESULTS: Mean age of interviewees was 35.4years (s.d.,10.2; range, 20-53). Every dimension of Robinson's model was spontaneously evoked, except for body image and spirituality. All men indicated intimacy/relationships (e.g. sexual agreements) and sexual health care/safer sex (e.g. HIV management, risk behaviours) as relevant aspects of sexual health. Other dimensions included: positive sexuality (n =7), such as pleasure and enjoyment during sex; talking about sex (n =5), which mainly concerned HIV disclosure; sexual functioning (n =4); challenges to sexual health (n =3), including substance abuse; and culture/sexual identity (n =3). Two participants (n =2) cited masturbation/fantasy. CONCLUSIONS: This study emphasises the multi-faceted nature of sexual health for gay men with HIV in serodifferent couples and the pivotal roles of relationships, HIV, risk management (e.g. via health care, knowledge), and positive sexual experiences. These dimensions could be considered in sexual health promotion interventions targeting this population.

Impact of social determinants of health on time to antiretroviral therapy initiation and HIV viral undetectability for migrants enrolled in a multidisciplinary HIV clinic with rapid, free, and onsite B/F/TAF: 'The ASAP study'.

OBJECTIVE: Multidisciplinary care with free, rapid, and on-site bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) dispensation may improve health outcomes among migrants living with HIV. However, models for rapid B/F/TAF initiation are not well studied among migrants living with HIV, and an understanding of how social determinants of health (SDH) may affect HIV-related health outcomes for migrants enrolled in such care models is limited. METHODS: Within a 96-week pilot feasibility prospective cohort study at a multidisciplinary HIV clinic, participants received free B/F/TAF rapidly after care linkage. The effects of SDH (i.e., birth region, sexual orientation, living status, education, employment, French proficiency, health coverage, use of a public health facility outside our clinic for free blood tests, and time in Canada) and other covariates (i.e., age, sex) on median time to antiretroviral therapy (ART) initiation and HIV viral undetectability from care linkage were calculated via survival analyses. RESULTS: Thirty-five migrants were enrolled in this study. Median time to ART initiation and HIV undetectability was 5 days (range 0-50) and 57 days (range 5-365), respectively. Those who took significantly longer to initiate ART were aged <35 years, identified as heterosexual, had less than university-level education, or were unemployed. No factor was found to significantly affect time to undetectability. CONCLUSION: Despite the provision of free B/F/TAF, several SDH were linked to delays in ART initiation. However, once initiated and engaged, migrants living with HIV reached HIV undetectability efficiently. Findings provide preliminary support for adopting this care model with migrants living with HIV and suggest that SDH should be considered when designing clinical interventions for more equitable outcomes.

Interventions, Barriers, and Facilitators to Address the Sexual Problems of Gay, Bisexual and Other Men Who Have Sex with Men Living with HIV: A Rapid Scoping Review.

Sexual problems are common among gay, bisexual, and other men who have sex with men (GBM) after diagnosis with HIV. However, these are often overlooked in care and research, where sexual risk reduction and biomedical aspects of sexual health tend to dominate. We conducted a rapid scoping review to investigate which sexual problems of GBM living with HIV are addressed by interventions, and the barriers and facilitators to their implementation. Literature from high-income countries published in English since 2010 was reviewed. Medline, Embase, PsycInfo, and Scopus databases were searched on July 4, 2022. Targeted sexual problems were categorized according to the ten dimensions of Robinson's Sexual Health Model, and barriers and facilitators, according to the five domains of the Consolidated Framework for Implementation Research (CFIR). Interventions focused solely on the dimension of Sexual Health Care/Safer Sex were excluded. Relevant information was extracted from the qualifying documents with NVivo 12 software for content analysis. Fifty-two documents were included, referring to 37 interventions which mainly took place in the United States (n = 29/37; 78%), were group-based (n = 16; 41%), and used counselling techniques (n = 23; 62%; e.g., motivational interviewing, cognitive-behavioral therapy). Their settings were mostly primary care (n = 15; 40%) or community-based (n = 16; 43%). On average, interventions addressed three sexual health dimensions (SD = 2; range: 1-10). The most targeted dimension was Sexual Health Care/Safer Sex (n = 26; 70%), which concerned sexual risk reduction. Next, Challenges (n = 23; 62%), included substance use (n = 7; 19%), sexual compulsivity (n = 6; 16%), sexual abuse (n = 6; 16%), and intimate partner violence (n = 4; 11%). Third was Talking About Sex (n = 22; 59%) which mostly concerned HIV disclosure. About a third of interventions addressed Culture/Sexual identity (n = 14; 38%), Intimacy/Relationships (n = 12; 33%), and Positive sexuality (n = 11; 30%). Finally, few targeted Body Image (n = 4; 11%), Spirituality (n = 3; 8%), Sexual Anatomy Functioning (n = 2; 5%) or Masturbation/Fantasy (n = 1; 3%). Forty-one documents (79%) mentioned implementation barriers or facilitators, particularly about the characteristics of the interventions (41% and 78%, respectively; e.g., cost, excessive duration, acceptability, feasibility) and of the individuals involved (37% and 46%; e.g., perceived stigmatization, provider expertise). The other three CFIR dimensions were less common (5%-17%). The search strategy of this review may not have captured all eligible documents, due to its limit to English-language publications. Overall, most interventions incorporated a focus on Sexual Health Care/Safer Sex, at the expenses of other prevalent sexual problems among GBM living with HIV, such as intimate partner violence (Challenges), erectile dysfunction (Sexual Anatomy Functioning), and Body Image dissatisfaction. These findings suggest they could receive more attention within clinical care and at the community level. They also highlight the importance of cost-effective and acceptable interventions conducted in non-stigmatizing environments, where patients' needs can be met by providers who are adequately trained on sexuality-related topics.

Patient-reported outcome measures in adult HIV care: A rapid scoping review of targeted outcomes and instruments used.

OBJECTIVE: There is international interest in the integration of patient-reported outcome measures (PROMs) into routine HIV care, but little work has synthesized the content of published initiatives. We conducted a rapid scoping review primarily to identify their selected patient-reported outcomes and respective instruments. METHODS: Four databases were searched on 4 May 2022 (Medline, Embase, CINAHL and PsychINFO) for relevant English language documents published from 2005 onwards. Dual review of at least 20% of records, full texts and data extraction was performed. Outcomes and instruments were classified with an adapted 14-domain taxonomy. Instruments with evidence of validation were described. RESULTS: Of 13 062 records generated for review, we retained a final sample of 94 documents, referring to 60 distinct initiatives led mostly in the USA (n = 29; 48% of initiatives), Europe (n = 16; 27%) and Africa (n = 9; 15%). The measured patient-reported outcome domains were: mental health (n = 42; 70%), substance use (n = 23; 38%), self-management (n = 16; 27%), symptoms (n = 12; 20%), sexual/reproductive health (n = 12; 20%), physical health (n = 9; 15%), treatment (n= 8; 13%), cognition (n = 7; 12%), quality of life (n = 7; 12%), violence/abuse (n = 6; 10%), stigma (n = 6; 10%), socioeconomic issues (n = 5; 8%), social support (n = 3; 5%) and body/facial appearance (n = 1; 2%). Initiatives measured 2.6 outcome domains, on average (range = 1-11). In total, 62 distinct validated PROMs were identified, with 53 initiatives (88%) employing at least one (M = 2.2). Overwhelmingly, the most used instrument was any version of the Patient Health Questionnaire to measure symptoms of depression, employed by over a third (26; 43%) of initiatives. CONCLUSION: Published PROM initiatives in HIV care have spanned 19 countries and disproportionately target mental health and substance use.

Switch to a raltegravir-based antiretroviral regimen in people with HIV and non-alcoholic fatty liver disease: A randomized controlled trial.

INTRODUCTION: The effect of antiretroviral therapy (ART), particularly integrase strand transfer inhibitors (INSTIs), on non-alcoholic fatty liver disease (NAFLD) in people with HIV remains unclear. We evaluated the effect of switching non-INSTI backbone antiretroviral medications to raltegravir on NAFLD and metabolic parameters. MATERIALS AND METHODS: This was a single-centre, phase IV, open-label, randomized controlled clinical trial. People living with HIV with NAFLD and undetectable viral load while receiving a non-INSTI were randomized 1:1 to the switch arm (raltegravir 400 mg twice daily) or the control arm (continuing ART regimens not containing INSTI). NAFLD was defined as hepatic steatosis by controlled attenuation parameter ≥238 dB/m in the absence of significant alcohol use and viral hepatitis co-infections. Cytokeratin 18 was used as a biomarker of non-alcoholic steatohepatitis. Changes over time in outcomes were quantified as standardized mean differences (SMDs), and a generalized linear mixed model was used to compare outcomes between study arms. RESULTS: A total of 31 people with HIV (mean age 54 years, 74% male) were randomized and followed for 24 months. Hepatic steatosis improved between baseline and end of follow-up in both the switch (SMD -43.4 dB/m) and the control arm (-26.6 dB/m); the difference between arms was not significant. At the end of follow-up, aspartate aminotransferase significantly decreased in the switch arm compared with the control arm (SMD -9.4 vs. 5.5 IU/L). No changes in cytokeratin 18, body mass index, or lipids were observed between study arms. DISCUSSION: Switching to a raltegravir-based regimen improved aspartate aminotransferase but seemed to have no effect on NAFLD, body weight, and lipids compared with remaining on any other ART.

Donating One's Body to HIV Cure Research Through Canadian Medical Assistance in Dying: A Case Study.

BACKGROUND: Finding a cure for HIV is challenged by persisting reservoirs, the mapping of which necessitates invasive procedures. Inviting people with HIV (PWHIV) at the end of life to donate body specimens post-mortem through research autopsies is a novel approach, raising ethical concerns. OBJECTIVE: This case study aims to explore the motivations, barriers, and facilitators of a terminally-ill Canadian PWHIV who requested medical assistance in dying (MAID) and expressed interest in donating his body for HIV cure research. CASE PRESENTATION: An in-depth 3-hour and semi-structured interview was conducted with the participant. The interview transcription was thematically coded to identify motivations and perceived barriers and facilitators to participate in end-of-life HIV cure research. Our analysis identified six themes. Two themes expressed motivations: Collaboration in progress in health and science, seeing cure research as collaboration with professionals; and Opportunity to learn more, mostly about science and health. One theme expressed a barrier: Losing interest in or identification with long-term care research matters, especially those related to the management of long-term care. Three themes expressed by facilitators: Receiving information from professionals one trusts and knows, especially clinical and research teams; Perceiving research procedures as simple, useful, and embedded in care, perceiving clinical, educational, and interpersonal benefits that surpass costs of participation; and Perceiving research as one last way to contribute, that is, feeling useful or give back. CONCLUSION: Several circumstances facilitated the patient's participation: being a single man, having time to participate, having no strong religious belief, and valuing clear, direct communication. His motivations to participate in HIV cure research were altruistic, and also an experience of working with clinical and research teams. Finally, this perspective highlights HIV cure research participant candidates' need for education about research procedures.

Role of fatty liver in the epidemic of advanced chronic liver disease among people with HIV: protocol for the Canadian LIVEHIV multicentre prospective cohort.

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.

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.

Effects of Oral Cannabinoids on Systemic Inflammation and Viral Reservoir Markers in People with HIV on Antiretroviral Therapy: Results of the CTN PT028 Pilot Clinical Trial.

Chronic HIV infection is characterized by persistent inflammation despite antiretroviral therapy (ART). Cannabinoids may help reduce systemic inflammation in people with HIV (PWH). To assess the effects of oral cannabinoids during HIV, ten PWH on ART were randomized (n = 5/group) to increasing doses of oral Δ9-tetrahydrocannabinol (THC): cannabidiol (CBD) combination (2.5:2.5-15:15 mg/day) capsules or CBD-only (200-800 mg/day) capsules for 12 weeks. Blood specimens were collected prospectively 7-21 days prior to treatment initiation and at weeks 0 to 14. Plasma cytokine levels were determined via Luminex and ELISA. Immune cell subsets were characterized by flow cytometry. HIV DNA/RNA were measured in circulating CD4 T-cells and sperm by ultra-sensitive qPCR. Results from both arms were combined for statistical analysis. Plasma levels of IFN-γ, IL-1ß, sTNFRII, and REG-3α were significantly reduced at the end of treatment (p ˂ 0.05). A significant decrease in frequencies of PD1+ memory CD4 T-cells, CD73+ regulatory CD4 T-cells, and M-DC8+ intermediate monocytes was also observed (p ˂ 0.05), along with a transient decrease in CD28-CD57+ senescent CD4 and CD8 T-cells. Ki-67+ CD4 T-cells, CCR2+ non-classical monocytes, and myeloid dendritic cells increased over time (p ˂ 0.05). There were no significant changes in other inflammatory markers or HIV DNA/RNA levels. These findings can guide future large clinical trials investigating cannabinoid anti-inflammatory properties.

Prognostic value of non-invasive scores based on liver stiffness measurement, spleen diameter and platelets in HIV-infected patients.

BACKGROUND AND AIMS: People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH. METHODS: We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC). RESULTS: We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis. CONCLUSIONS: Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone.

Fibroscan-Aspartate Aminotransferase Score Predicts Liver-Related Outcomes, but Not Extrahepatic Events, in a Multicenter Cohort of People With Human Immunodeficiency Virus.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is frequent in people with human immunodeficiency virus (PWH). The Fibroscan-aspartate aminotransferase (FAST) score was developed to identify patients with nonalcoholic steatohepatitis (NASH) and significant fibrosis. We investigated prevalence of NASH with fibrosis and the value of FAST score in predicting clinical outcomes in PWH. METHODS: Transient elastography (Fibroscan) was performed in PWH without viral hepatitis coinfection from 4 prospective cohorts. We used FAST >0.35 to diagnose NASH with fibrosis. Incidence and predictors of liver-related outcomes (hepatic decompensation, hepatocellular carcinoma) and extrahepatic events (cancer, cardiovascular disease) were evaluated through survival analysis. RESULTS: Of the 1472 PWH included, 8% had FAST >0.35. Higher body mass index (adjusted odds ratio [aOR], 1.21 [95% confidence interval {CI}, 1.14-1.29]), hypertension (aOR, 2.24 [95% CI, 1.16-4.34]), longer time since HIV diagnosis (aOR, 1.82 [95% CI, 1.20-2.76]), and detectable HIV RNA (aOR, 2.22 [95% CI, 1.02-4.85]) were associated with FAST >0.35. A total of 882 patients were followed for a median of 3.8 years (interquartile range, 2.5-4.2 years). Overall, 2.9% and 11.1% developed liver-related and extrahepatic outcomes, respectively. Incidence of liver-related outcomes was higher in patients with FAST >0.35 versus FAST ≤0.35 (45.1 [95% CI, 26.2-77.7] vs 5.0 [95% CI, 2.9-8.6] per 1000 person-years). FAST >0.35 remained an independent predictor of liver-related outcomes (adjusted hazard ratio, 4.97 [95% CI, 1.97-12.51]). Conversely, FAST did not predict extrahepatic events. CONCLUSIONS: A significant proportion of PWH may have NASH with significant liver fibrosis. FAST score predicts liver-related outcomes and can help management of this high-risk population.

Public health interventions, priority populations, and the impact of COVID-19 disruptions on hepatitis C elimination among people who have injected drugs in Montreal (Canada): A modeling study.

BACKGROUND: In Montreal (Canada), high hepatitis C virus (HCV) seroincidence (21 per 100 person-years in 2017) persists among people who have injected drugs (PWID) despite relatively high testing rates and coverage of needle and syringe programs (NSP) and opioid agonist therapy (OAT). We assessed the potential of interventions to achieve HCV elimination (80% incidence reduction and 65% reduction in HCV-related mortality between 2015 and 2030) in the context of COVID-19 disruptions among all PWID and PWID living with HIV. METHODS: Using a dynamic model of HCV-HIV co-transmission, we simulated increases in NSP (from 82% to 95%) and OAT (from 33% to 40%) coverage, HCV testing (every 6 months), or treatment rate (100 per 100 person-years) starting in 2022 among all PWID and PWID living with HIV. We also modeled treatment scale-up among active PWID only (i.e., people who report injecting in the past six months). We reduced intervention levels in 2020-2021 due to COVID-19-related disruptions. Outcomes included HCV incidence, prevalence, and mortality, and proportions of averted chronic HCV infections and deaths. RESULTS: COVID-19-related disruptions could have caused temporary rebounds in HCV transmission. Further increasing NSP/OAT or HCV testing had little impact on incidence. Scaling-up treatment among all PWID achieved incidence and mortality targets among all PWID and PWID living with HIV. Focusing treatment on active PWID could achieve elimination, yet fewer projected deaths were averted (36% versus 48%). CONCLUSIONS: HCV treatment scale-up among all PWID will be required to eliminate HCV in high-incidence and prevalence settings. Achieving elimination by 2030 will entail concerted efforts to restore and enhance pre-pandemic levels of HCV prevention and care.

Barriers to adherence to antiretroviral therapy: identifying priority areas for people with HIV and healthcare professionals.

BACKGROUND: Challenges to antiretroviral therapy adherence are well-known and continue to be a major hurdle in HIV care. The objective of this paper is to identify barriers to antiretroviral therapy (ART) adherence that are relevant to HIV care from the perspective of people living with HIV and healthcare and social service professionals. METHODS: This study used an online survey design to collect information from the two groups. A total of 100 areas that covered six domains and 20 subdomains were administered to people living with HIV and care professionals in Canada and France. The survey asked participants to rate the importance of each area for HIV care on a four-point Likert scale. Any areas rated 3 or 4 were considered important and ranked. A Chi-square test was conducted for the difference between the groups, people living with HIV and professionals, and between women and men. RESULTS: A response rate of 87% (58/66) in Canada and 65% (38/58) was achieved. 15 of 43 (35%) areas were endorsed as important barriers by both groups, across countries and sex-covering subdomains - drug cost coverage, challenging material circumstances, HIV stigma, and privacy concerns, affect, motivation, beliefs, acceptance of HIV, comorbidity, side effects, and demands and organisation of daily life. People living with HIV identified two, and care professionals identified nine, additional areas as important barriers to HIV care across different domains and subdomains. CONCLUSION: The study identified some common and distinct barriers to ART from the perspective of the people living with HIV and care professionals.

"Live a normal life": Constructions of resilience among people in mixed HIV status relationships in Canada.

Positive Plus One is a mixed-methods study of long-term mixed HIV-serostatus relationships in Canada (2016-19). Qualitative interviews with 51 participants (10 women, 41 men, including 27 HIV-positive and 24 HIV-negative partners) were analyzed using inductive thematic analysis to examine notions of relationship resilience in the context of emerging HIV social campaigns. Relationship resilience meant finding ways to build and enact life as a normal couple, that is, a couple not noticeably affected by HIV, linked to the partner with HIV maintaining viral suppression and achieving "undetectable = untransmittable" (U = U). Regardless of serostatus, participants with material resources, social networks, and specialized care were better able to construct resilience for HIV-related challenges within their relationships. Compared to heterosexual couples and those facing socioeconomic adversity, gay and bisexual couples were easier able to disclose, and access capital, networks and resources supporting resilience. We conclude that important pathways of constructing, shaping, and maintaining resilience were influenced by the timing of HIV diagnosis in the relationship, access to HIV-related information and services, disclosure, stigma and social acceptance.

Influence of letermovir treatment on gut inflammation in people living with HIV on antiretroviral therapy: protocol of the open-label controlled randomised CIAO study.

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 <50 copies/mL and CD4+ count >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.

Disclosure of HIV-serodiscordant relationships and association with viral suppression: results from the Positive Plus One study.

BACKGROUND: Little is known about the effects of disclosure of HIV-serodiscordant relationships on clinical outcomes. We aimed to evaluate the effect of relationship disclosure on HIV viral suppression, and hypothesized that disclosure by HIV-positive and HIV-negative partners would be associated with viral suppression in the HIV-positive partner. METHODS: We conducted a Canadian national online and telephone-administered survey of HIV-positive and HIV-negative partners in serodiscordant relationships. The primary outcome was self-reported viral suppression. Multivariable analyses were undertaken using Firth logistic regression. RESULTS: We recruited 540 participants in current serodiscordant relationships (n = 228 HIV-negative; n = 312 HIV-positive). Similar proportions of HIV-positive and HIV-negative partners disclosed their relationship to healthcare professionals (82% v. 76%, p = 0.13). Among HIV-positive partners, disclosure of the relationship to healthcare professionals increased the odds of viral suppression (aOR = 4.7; CI: 2.13, 10.51) after adjusting for age, education, and relationship turmoil due to HIV. Increasing age (aOR = 1.28; 95% CI = 1.07, 1.55) and education (aOR = 2.43; 95% CI = 1.15, 5.26) were also associated with viral suppression. Among HIV-negative partners, relationship disclosure was not associated with viral suppression and HIV-negative heterosexual men were less likely to report that their HIV-positive partners were virally suppressed (aOR = 0.24; CI: 0.09, 0.61). CONCLUSIONS: Disclosure of HIV-serodiscordant status by HIV-positive participants to healthcare professionals was associated with increased odds of viral suppression. Similar effects were not evident among HIV-negative participants. Future work should explore factors that empower relationship disclosure and incorporate them into supportive services for HIV-serodiscordant relationships.

Implementation of Lost & Found, An Intervention to Reengage Patients Out of HIV Care: A Convergent Explanatory Sequential Mixed-Methods Analysis.

Being out of HIV care (OOC) is associated with increased morbidity and mortality. We assessed implementation of Lost & Found, a clinic-based intervention to reengage OOC patients. OOC patients were identified using a nurse-validated, real-time OOC list within the electronic medical records (EMR) system. Nurses called OOC patients. Implementation occurred at the McGill University Health Centre from April 2018 to 2019. Results from questionnaires to nurses showed elevated scores for implementation outcomes throughout, but with lower, more variable scores during pre-implementation to month 3 [e.g., adoption subscales (scale: 1-5): range from pre-implementation to month 3, 3.7-4.9; thereafter, 4.2-4.9]. Qualitative results from focus groups with nurses were consistent with observed quantitative trends. Barriers concerning the EMR and nursing staff shortages explained reductions in fidelity. Strategies for overcoming barriers to implementation were crucial in early months of implementation. Intervention compatibility, information systems support, as well as nurses' team processes, knowledge, and skills facilitated implementation.