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.

IL-32 Drives the Differentiation of Cardiotropic CD4+ T Cells Carrying HIV DNA in People With HIV.

Interleukin 32 (IL-32) is a potent multi-isoform proinflammatory cytokine, which is upregulated in people with HIV (PWH) and is associated with cardiovascular disease (CVD) risk. However, the impact of IL-32 isoforms on CD4 T-cell cardiotropism, a mechanism potentially contributing to heart inflammation, remains unknown. Here we show that IL-32 isoforms ß and γ induce the generation of CCR4+CXCR3+ double positive (DP) memory CD4 T-cell subpopulation expressing the tyrosine kinase receptor c-Met, a phenotype associated with heart-homing of T cells. Our ex vivo studies on PWH show that the frequency of DP CD4 T cells is significantly higher in individuals with, compared to individuals without, subclinical atherosclerosis and that DP cells from antiretroviral-naive and treated individuals are highly enriched with HIV DNA. Together, these data demonstrate that IL-32 isoforms have the potential to induce heart-homing of HIV-infected CD4 T cells, which may further aggravate heart inflammation and CVD in PWH.

Population-level effectiveness of pre-exposure prophylaxis for HIV prevention among men who have sex with men in Montréal (Canada): a modelling study of surveillance and survey data.

INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) has been recommended and partly subsidized in Québec, Canada, since 2013. We evaluated the population-level impact of PrEP on HIV transmission among men who have sex with men (MSM) in Montréal, Québec's largest city, over 2013-2021. METHODS: We used an agent-based mathematical model of sexual HIV transmission to estimate the fraction of HIV acquisitions averted by PrEP compared to a counterfactual scenario without PrEP. The model was calibrated to local MSM survey, surveillance, and cohort data and accounted for COVID-19 pandemic impacts on sexual activity, HIV prevention, and care. PrEP was modelled from 2013 onwards, assuming 86% individual-level effectiveness. The PrEP eligibility criteria were: any anal sex unprotected by condoms (past 6 months) and either multiple partnerships (past 6 months) or multiple uses of post-exposure prophylaxis (lifetime). To assess potential optimization strategies, we modelled hypothetical scenarios prioritizing PrEP to MSM with high sexual activity (≥11 anal sex partners annually) or aged ⩽45 years, increasing coverage to levels achieved in Vancouver, Canada (where PrEP is free-of-charge), and improving retention. RESULTS: Over 2013-2021, the estimated annual HIV incidence decreased from 0.4 (90% credible interval [CrI]: 0.3-0.6) to 0.2 (90% CrI: 0.1-0.2) per 100 person-years. PrEP coverage among HIV-negative MSM remained low until 2015 (<1%). Afterwards, coverage increased to a maximum of 10% of all HIV-negative MSM, or about 16% of the 62% PrEP-eligible HIV-negative MSM in 2020. Over 2015-2021, PrEP averted an estimated 20% (90% CrI: 11%-30%) of cumulative HIV acquisitions. The hypothetical scenarios modelled showed that, at the same coverage level, prioritizing PrEP to high sexual activity MSM could have averted 30% (90% CrI: 19%-42%) of HIV acquisitions from 2015-2021. Even larger impacts could have resulted from higher coverage. Under the provincial eligibility criteria, reaching 10% coverage among HIV-negative MSM in 2015 and 30% in 2019, like attained in Vancouver, could have averted up to 63% (90% CrI: 54%-70%) of HIV acquisitions from 2015 to 2021. CONCLUSIONS: PrEP reduced population-level HIV transmission among Montréal MSM. However, our study suggests missed prevention opportunities and adds support for public policies that reduce PrEP barriers, financial or otherwise, to MSM at risk of HIV acquisition.

Baseline characteristics of a prospective cohort study of aging and cardiovascular diseases among people living with HIV.

OBJECTIVES: Our objective was to report the baseline characteristics of participants in the Canadian HIV and Aging Cohort Study (CHACS) and present amendments to the initial protocol. METHODS: CHACS is a multi-centred prospective cohort study that was initially set from 2011 to 2016 and will now continue recruitment until 2024. Four additional years of follow-up have been added, and additional outcomes and covariates will be prospectively collected. Frailty will be assessed using a modified version of the Fried's frailty phenotype. The four interrelated aspects of gender-gender roles, gender identity, gender relationships, and institutionalized gender-will be measured using the GENESIS-PRAXY questionnaire. Diet will be assessed using a validated, web-based, self-administered food frequency questionnaire. RESULTS: A total of 1049 participants (77% people living with HIV) were recruited between September 2011 and September 2019. Median age at baseline was 54 years (interquartile range 50-61). Most participants were male (84%) and white (83%). Compared with participants without HIV, those with HIV were more likely to be male; to report lower education levels and incomes; to be more sedentary; to use tobacco, recreational, and prescription drugs; to report a personal history of cardiovascular diseases; and to be frail. CONCLUSIONS: The new assessments added to the CHACS protocol will allow for an even more detailed portrait of the pathways leading to accentuated aging for people living with HIV. Participants in the CHACS cohort display important differences in socio-economic and cardiovascular risk factors according to HIV serostatus. These imbalances must be taken into account for all further inferential analyses.

Control of porphyria cutanea tarda with anti-IL-17 secukinumab in a person with psoriasis living with HIV.

A 65-year-old woman successfully treated for human immunodeficiency virus (HIV) and Hepatitis C virus was diagnosed with porphyria cutanea tarda (PCT) and treated by phlebotomies. She developed extensive psoriatic skin lesions resistant to topical treatments and methotrexate. She then received the anti-interleukin-17 (IL-17) secukinumab (Cosentyx) which improved her psoriatic skin lesions. Unexpectedly, her PCT skin lesions healed, allowing phlebotomy discontinuation over 2 years. Without lesions, the patient decided to discontinue secukinumab, leading to the recurrence of psoriatic and PCT skin lesions, which were controlled upon therapeutical rechallenge. No AIDS-related manifestations or infections developed, her CD4 count remained elevated and her HIV viral load was controlled under antiretroviral therapy. Both skin conditions and consequently the patient's quality of life have improved with secukinumab, allowing exposure to sunlight and phlebotomy discontinuation for >4 years. Likely, the IL-17 pathway is involved in the clinical manifestations of PCT, opening new avenues for therapeutical interventions.

Doravirine responses to HIV-1 viruses bearing mutations to NRTIs and NNRTIs under in vitro selective drug pressure.

OBJECTIVES: The NNRTI doravirine has been recently approved for the first-line treatment of HIV-infected patients, eliciting favourable responses against viruses bearing the K103N, Y181C and G190A mutations. This study used in vitro drug selections to elaborate the breadth of doravirine responses against viruses bearing NNRTI and NRTI resistance-associated mutations (RAMs). METHODS: WT clinical isolates (n = 6) and viruses harbouring common NRTI and NNRTI RAMs (n = 6) were serially passaged in escalating concentrations of doravirine, doravirine/islatravir, doravirine/lamivudine and rilpivirine over 24 weeks. Genotypic analysis ascertained the appearance and accumulation of NNRTI RAMs. Phenotypic drug susceptibility assays assessed resistance conferred by acquired NNRTI RAMs. RESULTS: For WT viruses, doravirine pressure led to the appearance of V108I or V106A/I/M RAMs after 8 weeks, conferring low-level (∼2-fold) resistance. After 24 weeks, the accumulation of three to six secondary RAMs, including F227L, M230L, L234I and/or Y318, resulted in high-level (>100-fold) resistance to doravirine. Notably, viruses with these doravirine RAMs remained susceptible to rilpivirine and efavirenz. This contrasted with rilpivirine where acquisition of E138K, L100I and/or K101E resulted in >50-fold cross-resistance to all NNRTIs. Doravirine selection of viruses bearing common NRTI and NNRTI RAMs showed delayed acquisition of RAMs compared with WT virus. Pairing doravirine with islatravir or lamivudine attenuated the development of NNRTI RAMs. CONCLUSIONS: Doravirine showed favourable resistance profiles against viruses harbouring NRTI and NNRTI RAMs. The high barrier to resistance to doravirine coupled with the long intracellular half-life of islatravir may provide the opportunity for long-acting treatment options.

Differential Impact of IL-32 Isoforms on the Functions of Coronary Artery Endothelial Cells: A Potential Link with Arterial Stiffness and Atherosclerosis.

Chronic inflammation is associated with higher risk of cardiovascular disease (CVD) in people living with HIV (PLWH). We have previously shown that interleukin-32 (IL-32), a multi-isoform proinflammatory cytokine, is chronically upregulated in PLWH and is linked with CVD. However, the mechanistic roles of the different IL-32 isoforms in CVD are yet to be identified. In this study, we aimed to investigate the potential impact of IL-32 isoforms on coronary artery endothelial cells (CAEC), whose dysfunction represents a major factor for atherosclerosis. Our results demonstrated that the predominantly expressed IL-32 isoforms (IL-32ß and IL-32γ) have a selective impact on the production of the proinflammatory cytokine IL-6 by CAEC. Furthermore, these two isoforms induced endothelial cell dysfunction by upregulating the expression of the adhesion molecules ICAM-I and VCAM-I and the chemoattractants CCL-2, CXCL-8 and CXCL-1. IL-32-mediated expression of these chemokines was sufficient to drive monocyte transmigration in vitro. Finally, we demonstrate that IL-32 expression in both PLWH and controls correlates with the carotid artery stiffness, measured by the cumulated lateral translation. These results suggest a role for IL-32-mediated endothelial cell dysfunction in dysregulation of the blood vessel wall and that IL-32 may represent a therapeutic target to prevent CVD in PLWH.

Phenotypic characterization of single CD4+ T cells harboring genetically intact and inducible HIV genomes.

The phenotype of the rare HIV-infected cells persisting during antiretroviral therapies (ART) remains elusive. We developed a single-cell approach that combines the phenotypic analysis of HIV-infected cells with near full-length sequencing of their associated proviruses to characterize the viral reservoir in 6 male individuals on suppressive ART. We show that individual cells carrying clonally expanded identical proviruses display very diverse phenotypes, indicating that cellular proliferation contributes to the phenotypic diversification of the HIV reservoir. Unlike most viral genomes persisting on ART, inducible and translation-competent proviruses rarely present large deletions but are enriched in defects in the Ψ locus. Interestingly, the few cells harboring genetically intact and inducible viral genomes express higher levels of the integrin VLA-4 compared to uninfected cells or cells with defective proviruses. Viral outgrowth assay confirmed that memory CD4+ T cells expressing high levels of VLA-4 are highly enriched in replication-competent HIV (27-fold enrichment). We conclude that although clonal expansions diversify the phenotype of HIV reservoir cells, CD4+ T cells harboring replication-competent HIV retain VLA-4 expression.

CD4/CD8 Ratio Outcome According to the Class of the Third Active Drug in Antiretroviral Therapy Regimens: Results From the Quebec Human Immunodeficiency Virus Cohort Study.

BACKGROUND: The impact of different therapeutic classes of drugs in antiretroviral therapy (ART) regimens on the CD4/CD8 ratio is not well documented in people treated for HIV. The objective of this study was to analyze the long-term effect of exposure to integrase strand transfer inhibitor (INSTI) on CD4/CD8 ratio compared with nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) among ART-treated persons with HIV (PWH). METHODS: Data from the Quebec HIV Cohort collected from 31 August 2017 were used. Our analysis included all patients in the cohort who received a first or subsequent ART regimen composed of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and a third active drug of a different class (NNRTI, PI, or INSTI) for at least 16 weeks. Marginal structural Cox models were constructed to estimate the effect of different therapeutic classes on the CD4/CD8 ratio outcome. RESULTS: Among the 3907 eligible patients, 972 (24.9%), 1996 (51.1%), and 939 (24.0%) were exposed to an ART regimen whose third active agent was an NNRTI, PI, or INSTI, respectively. The total follow-up time was 13 640.24 person-years. The weighted hazard ratio for the association between the third active class and CD4/CD8 ratio ≥1 was .56 (95% confidence interval [CI]: .48-.65) for patients exposed to NNRTI + 2 NRTIs and .41 (95% CI: .35-.47) for those exposed to PI + 2 NRTIs, compared with those exposed INSTI + 2 NRTIs. CONCLUSIONS: For people treated for HIV, INSTI-based ART appears to be associated with a higher CD4/CD8 ratio than NNRTI and PI-based ART.

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.

Monkeypox in Montréal: Epidemiology, Phylogenomics, and Public Health Response to a Large North American Outbreak.

BACKGROUND: Monkeypox, a viral zoonotic disease, is causing a global outbreak outside of endemic areas. OBJECTIVE: To characterize the outbreak of monkeypox in Montréal, the first large outbreak in North America. DESIGN: Epidemiologic and laboratory surveillance data and a phylogenomic analysis were used to describe and place the outbreak in a global context. SETTING: Montréal, Canada. PATIENTS: Probable or confirmed cases of monkeypox. MEASUREMENTS: Epidemiologic, clinical, and demographic data were aggregated. Whole-genome sequencing and phylogenetic analysis were performed for a set of outbreak sequences. The public health response and its evolution are described. RESULTS: Up to 18 October 2022, a total of 402 cases of monkeypox were reported mostly among men who have sex with men (MSM), most of which were suspected to be acquired through sexual contact. All monkeypox genomes nested within the B.1 lineage. Montréal Public Health worked closely with the affected communities to control the outbreak, becoming the first jurisdiction to offer 1 dose of the Modified Vaccinia Ankara-Bavarian Nordic vaccine as preexposure prophylaxis (PrEP) to those at risk in early June 2022. Two peaks of cases were seen in early June and July (43 and 44 cases per week, respectively) followed by a decline toward near resolution of the outbreak in October. Reasons for the biphasic peak are not fully elucidated but may represent the tempo of vaccination and/or several factors related to transmission dynamics and case ascertainment. LIMITATIONS: Clinical data are self-reported. Limited divergence among sequences limited genomic epidemiologic conclusions. CONCLUSION: A large outbreak of monkeypox occurred in Montréal, primarily among MSM. Successful control of the outbreak rested on early and sustained engagement with the affected communities and rapid offer of PrEP vaccination to at-risk persons. PRIMARY FUNDING SOURCE: None.

Effect of autogenic training on quality of life and symptoms in people living with HIV: A mixed method randomized controlled trial.

OBJECTIVE: Quality of life of people living with HIV is strongly affected by sleep problems, fatigue, pain, anxiety, and depression symptoms. This study set out to evaluate the effects of autogenic training (AT) on quality of life and symptoms within this population. METHODS: A mixed method randomized controlled trial was conducted. Participants were randomly assigned to either the AT group (n = 32) or the control group (CG) (n = 31). Quality of life and symptoms were measured in both groups three times: prior to intervention (T0), immediately after intervention (T3), and three months after intervention (T6). Fourteen individual interviews were conducted. RESULTS: Results show a significant improvement in social and mental dimensions of quality of life for the two groups at T6. They also show a significant improvement in sleep for AT participants at T3. Qualitative results are consistent with quantitative ones. CONCLUSION: AT seems to improve sleep quality and could improve some dimensions of quality of life and other symptoms among people living with HIV. Further studies are needed to confirm these results. TRIAL REGISTRATION NUMBER: NCT01901016.

Association Between the Development of Subclinical Cardiovascular Disease and Human Immunodeficiency Virus (HIV) Reservoir Markers in People With HIV on Suppressive Antiretroviral Therapy.

We report that people with human immunodeficiency virus (HIV) diagnosed with coronary artery atherosclerotic plaques display higher levels of HIV DNA compared with those without atherosclerotic plaques. In a multivariable prediction model that included 27 traditional and HIV-related risk factors, measures of HIV DNA were among the most important predictors of atherosclerotic plaque formation.

Safety and Tolerability of Oral Cannabinoids in People Living with HIV on Long-Term ART: A Randomized, Open-Label, Interventional Pilot Clinical Trial (CTNPT 028).

BACKGROUND: With anti-inflammatory properties, cannabinoids may be a potential strategy to reduce immune activation in people living with HIV (PLWH) but more information on their safety and tolerability is needed. METHODS: We conducted an open-label interventional pilot study at the McGill University Health Centre in Montreal, Canada. PLWH were randomized to oral Δ9-tetrahydrocannabinol (THC): cannabidiol (CBD) combination (THC 2.5 mg/CBD 2.5 mg) or CBD-only capsules (CBD 200 mg). Individuals titrated doses as tolerated to a maximum daily dose THC 15 mg/CBD 15 mg or 800 mg CBD, respectively, for 12 weeks. The primary outcome was the percentage of participants without any significant toxicity based on the WHO toxicity scale (Grades 0-2 scores). RESULTS: Out of ten individuals, eight completed the study. Two from the CBD-only arm were withdrawn for safety concerns: phlebotomy aggravating pre-existing anemia and severe hepatitis on 800 mg CBD with newly discovered pancreatic adenocarcinoma, respectively. Seven did not have any significant toxicity. Cannabinoids did not alter hematology/biochemistry profiles. CD4 count, CD4/CD8 ratio, and HIV suppression remained stable. Most adverse effects were mild-moderate. CONCLUSIONS: In PLWH, cannabinoids seem generally safe and well-tolerated, though larger studies are needed. Screening for occult liver pathology should be performed and hepatic enzymes monitored, especially with high CBD doses.

Trends in Use of Combination Antiretroviral Therapy and Treatment Response from 2000 to 2016 in the Canadian Observational Cohort (CANOC): A Longitudinal Cohort Study.

Background: Advances in treatment have turned HIV from a terminal illness to a more manageable condition. Over the past 20 years, there have been considerable changes to HIV treatment guidelines, including changes in preferred antiretrovirals and timing of initiation of combination antiretroviral therapy (cART). Objective: To examine real-world trends in cART utilization, viral control, and immune reconstitution among people living with HIV in Canada. Methods: Data were obtained from the Canadian Observational Cohort (CANOC). CANOC participants were eligible if they were antiretroviral therapy-naive at entry and initiated 3 or more antiretrovirals on or after January 1, 2000; if they were at least 18 years of age at treatment initiation; if they were residing in Canada; and if they had at least 1 viral load determination and CD4 count within 1 year of CANOC entry. Baseline and annual mean CD4 counts were categorized as less than 200, 200-350, 351-500, and more than 500 cells/mm3. Annual mean viral loads were reported as suppressed (< 50 copies/mL), low (50-199 copies/mL), or high detectable (≥ 200 copies/mL). The cART regimens were reported yearly. Results: All CANOC participants were included (n = 13 040). Over the study period, the proportion of individuals with an annual mean CD4 count above 500 cells/mm3 increased from 16.3% to 65.8%, while the proportion of individuals with an undetectable mean viral load increased from 10.6% to 83.2%. As of 2007, the most commonly prescribed 2-agent nucleoside reverse transcriptase inhibitor backbone was tenofovir disoproxil fumarate and emtricitabine. In terms of third agents, non-nucleoside reverse transcriptase inhibitors were the most common class in the periods 2000-2003 and 2014-2015, protease inhibitors were most common in the period 2004-2013, and integrase inhibitors were most common in 2016. Conclusions: Concordance with treatment guidelines was demonstrated over time with respect to cART prescribing and immunologic and virologic response.

Contexte: Les progrès effectués dans le domaine des traitements ont transformé le VIH. Celui-ci est passé d'une maladie en phase terminale à une maladie plus gérable. Au cours des 20 dernières années, des changements considérables ont eu lieu dans les directives de traitement du VIH, y compris des changements dans les antirétroviraux privilégiés et le moment de l'initiation de la thérapie antirétrovirale combinée (TARc). Objectif: Examiner les tendances réelles de l'utilisation de la TARc, du contrôle viral et de la reconstitution immunitaire chez les personnes vivant avec le VIH au Canada. Méthodes: Les données ont été obtenues auprès de la Canadian Observational Cohort (CANOC). Les participants à la CANOC étaient admissibles s'ils n'avaient jamais reçu de traitement antirétroviral à l'entrée et avaient commencé la prise de 3 antirétroviraux ou plus le 1er janvier 2000 ou après cette date; s'ils avaient au moins 18 ans au moment du début du traitement; s'ils résidaient au Canada; et s'ils avaient au moins 1 charge virale et un nombre de CD4 dans l'année suivant l'entrée à la CANOC. Les numérations initiales et annuelles moyennes de CD4 ont été classées comme inférieures à 200, 200 à 350, 351 à 500, et supérieures à 500 cellules/mm3. Les charges virales moyennes annuelles ont été signalées comme supprimées (< 50 copies/mL), faibles (50 à 199 copies/mL) ou élevées détectables (≥ 200 copies/mL). Les régimes de la TARc ont été rapportés chaque année. Résultats: Tous les participants à la CANOC ont été inclus (n = 13040). Au cours de la période d'étude, la proportion de personnes ayant une numération CD4 moyenne annuelle supérieure à 500 cellules/mm3 est passée de 16,3 % à 65,8 %, tandis que la part de personnes ayant une charge virale moyenne indétectable est passée de 10,6 % à 83,2 %. En 2007, la bithérapie de base d'inhibiteurs nucléosidiques de la transcriptase inverse la plus couramment prescrite était le fumarate de ténofovir disoproxil et l'emtricitabine. En matière de troisièmes agents, la classe la plus courante dans les périodes 2000­2003 et 2014­2015 était les inhibiteurs non nucléosidiques de la transcriptase inverse; les plus courants dans la période 2004­2013 étaient les inhibiteurs de protéase; et les inhibiteurs de l'intégrase étaient les plus courants en 2016. Conclusions: La concordance avec les directives de traitement a été démontrée au fil du temps en ce qui concerne la prescription de la cART et la réponse immunologique et virologique.

Cross-sectional comparison of age- and gender-related comorbidities in people living with HIV in Canada.

Because antiretroviral therapy (ART) is allowing people living with human immunodeficiency virus (PLWH) to survive longer, they are developing more age-related comorbidities. We evaluated the effects of age and gender on the burden of age-related comorbidities among PLWH. In this retrospective real-world study, de-identified data were extracted from the medical charts of 2000 HIV-positive adults on ART across 10 sites in Canada. The prevalence of age-related comorbidities was determined in 6 age subgroups (<30, 30-39, 40-49, 50-59, 60-69, and ≥70 years). The effects of gender on these comorbidities were also examined. Risks of cardiovascular disease and chronic kidney disease (CKD) were calculated using the Framingham and D:A:D equations. Most persons were White (68%), male (87%), and virologically suppressed (94%). The mean age was 50.3 years (57% aged ≥50 years), and mean CD4+ T-cell count was 616 cells/mm3. The most common comorbidities were neuropsychiatric symptoms (61%), overweight/obesity (43%), liver disease (37%), and dyslipidemia (37%). The mean number of comorbidities increased across age subgroups (P < .001). Across all age subgroups, the prevalence of hypertension (P = .04), dyslipidemia (P = .04), CKD (P = .03), bone fragility (P = .03), and depression (P = .02) differed between males and females. Both age (P < .001) and gender (P < .001) impacted cardiovascular disease and CKD risk. Age and gender influenced the burden, types, and risks of age-related comorbidities in PLWH in this Canadian cohort. These comorbidities should be diagnosed and treated in routine clinical practice.

Past dynamics of HIV transmission among men who have sex with men in Montréal, Canada: a mathematical modeling study.

BACKGROUND: Gay, bisexual, and other men who have sex with men (gbMSM) experience disproportionate risks of HIV acquisition and transmission. In 2017, Montréal became the first Canadian Fast-Track City, setting the 2030 goal of zero new HIV infections. To inform local elimination efforts, we estimate the evolving role of prevention and sexual behaviours on HIV transmission dynamics among gbMSM in Montréal between 1975 and 2019. METHODS: Data from local bio-behavioural surveys were analyzed to develop, parameterize, and calibrate an agent-based model of sexual HIV transmission. Partnership dynamics, HIV's natural history, and treatment and prevention strategies were considered. The model simulations were analyzed to estimate the fraction of HIV acquisitions and transmissions attributable to specific groups, with a focus on age, sexual partnering level, and gaps in the HIV care-continuum. RESULTS: The model-estimated HIV incidence peaked in 1985 (2.3 per 100 person years (PY); 90% CrI: 1.4-2.9 per 100 PY) and decreased to 0.1 per 100 PY (90% CrI: 0.04-0.3 per 100 PY) in 2019. Between 2000-2017, the majority of HIV acquisitions and transmissions occurred among men aged 25-44 years, and men aged 35-44 thereafter. The unmet prevention needs of men with > 10 annual anal sex partners contributed 90-93% of transmissions and 67-73% of acquisitions annually. The primary stage of HIV played an increasing role over time, contributing to 11-22% of annual transmissions over 2000-2019. In 2019, approximately 70% of transmission events occurred from men who had discontinued, or never initiated antiretroviral therapy. CONCLUSIONS: The evolving HIV landscape has contributed to the declining HIV incidence among gbMSM in Montréal. The shifting dynamics identified in this study highlight the need for continued population-level surveillance to identify gaps in the HIV care continuum and core groups on which to prioritize elimination efforts.

The process of learning the autogenic training relaxation technique and its benefits on the wellness of people living with HIV.

BACKGROUND: Various mind-body practices are used by people living with HIV to promote their general well-being. Among these is autogenic training (AT), a self-guided relaxation technique requiring regular practice for observable benefits. However, little has been written about the process of learning this technique, which is obviously a prerequisite to regular practice. This study therefore aims to describe the process by which people living with HIV learn AT. METHODS: The study is a descriptive qualitative study using semi-structured interviews and a thematic analysis with a mixed approach. Fourteen participants living with HIV completed sessions to learn autogenic training over a period of 3 months. RESULTS: The process of learning AT was approached through three themes: initiating the learning process, taking ownership of the technique, and observing its benefits on wellness. To initiate learning, participants had to express a need to take action on an aspect of their well-being and their openness to complementary approaches to care. Taking ownership of the technique was facilitated by guidance from the nurse researcher, the participants' personal adaptations to overcome barriers to their practice, regular practice, and rapid observation of its benefits. Finally, the participants reported the observation of benefits on their wellness, including personal development, mainly in terms of the creative self, the essential self, and the coping self. This perception of the technique's benefits was part of the learning process, as it contributed both to the participants' ownership of the technique and to reinforcing their AT practice. CONCLUSIONS: People living with HIV see learning AT as a progressive process, in which wellness is a major outcome and a contributing factor in developing a regular practice.

Factors partitioning physical frailty in people aging with HIV: A classification and regression tree approach.

OBJECTIVE: To estimate the extent to which comorbidity and lifestyle factors were associated with physical frailty in middle-aged and older Canadians living with HIV. DESIGN: Cross-sectional analysis of 856 participants from the Canadian Positive Brain Health Now cohort. METHODS: The frailty indicator phenotype was adapted from Fried's criteria using self-report items. Univariate logistic regression and classification and regression tree (CaRT) models were used to identify the most relevant independent contributors to frailty. RESULTS: In all, 100 men (14.0%) and 26 women (19.7%) were identified as frail (≥ 3/5 criteria) for an overall prevalence of 15.2%. Nine comorbidities showed an influential association with frailty. The most influential comorbidities were hypothyroidism [odds ratio (OR) = 2.55, 95% confidence interval (CI): 1.29-5.03] and arthritis (OR = 2.54, 95% CI: 1.58-4.09). Additionally, tobacco (OR = 1.79, 95% CI: 1.05-3.04) showed an association. Any level of alcohol consumption showed a protective effect for frailty. The CaRT model showed nine pathways that led to frailty. Arthritis was the most discriminatory variable followed by alcohol, hypothyroidism, tobacco, cancer, cannabis, liver disease, kidney disease, osteoporosis, lung disease and peripheral vascular disease. The prevalence of physical frailty for people with arthritis was 27.4%; with additional cancer or tobacco and alcohol the prevalence rates were 47.1% and 46.1%, respectively. The protective effect of alcohol consumption evident in the univariate model appeared again in the CaRT model, but this effect varied. Cognitive frailty (19.5% overall) and emotional frailty (37.9% overall) were higher than the prevalence of physical frailty. CONCLUSIONS: Specific comorbidities and tobacco use were implicated in frailty, suggesting that it is comorbidities causing frailty. However, some frailty still appears to be HIV-related. The higher prevalence of cognitive and emotional frailty highlights the fact that physical frailty should not be the only focus in HIV.

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.