Explore the vast range of titles available.

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. Some HIV-infected cells persist during antiretroviral therapies (ART) but their phenotype is less clear. Dufour et al. show that HIV-infected cells that persist in people receiving ART are phenotypically diverse and that CD4+ T cells expressing the integrin VLA-4 are highly enriched in replication-competent HIV.

In 2020, compared against the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets for HIV elimination (95% tested for HIV, 95% treated and 95% retained in treatment), Canada stands at 86% tested, 81% treated, 91% retained in treatment. Despite the availability of HIV testing, about 14%-20% of Canadians infected with HIV are not aware that they are infected. Undetected HIV burden is high in specific populations such as Indigenous people, people who inject drugs, immigrants and men who have sex with men. The latest HIV surveillance data in Quebec reported that 25.5% of individuals who received a new diagnosis of HIV in 2018 had a CD4 level of less than 200/mm3. Finally, large-scale Canadian trials and cost-effectiveness studies evaluating the implementation of HIVST are needed to guide the formulation of federal and provincial HIVST-specific policies and guidelines. Introduction of HIVST in Canada should lead to better detection of HIV in underdiagnosed populations who currently face barriers to testing, as well as improve HIV management, bringing us closer to the UNAIDS 95-95-95 targets.

Characterization of populations at risk of acquiring HIV is required to inform the public health response to HIV. To identify potential changing needs in HIV prevention and care cascade, we aim to describe how the demographic profiles and exposure categories of newly diagnosed HIV positive individuals attending a large sexual health clinic in Montréal (Canada) evolved since the beginning of the antiretroviral therapy era in the mid-1990s. Using diagnosis data from participants of the Clinique médicale l'Actuel cohort of HIV-positive patients, we examined the distribution of exposure categories (sexual orientation, sexual behaviours, injection drug use, being born in an HIV-endemic country) by gender and year of diagnosis. Time trends in mean age and in the proportion of patients with late (CD4 <350 cells/μL) or advanced stage (CD4 <200 cells/μL) of HIV infection at diagnosis were assessed through meta-regressions. A total of 2,612 patients diagnosed with HIV between January 1st, 1995 and December 31st, 2019 were included. Overall, mean age was 35 years (standard deviation: 10 years) and remained stable over time. The proportion of patients with advanced stage of HIV infection decreased from 16% in 1995 to 4% in 2019. Although men who have sex with men (MSM) consistently accounted for the highest proportion of new diagnoses (77%, 2,022/2,612 overall), their proportion decreased since 2013. There was also a concomitant decrease in the proportion of people who inject drugs, with none of the newly diagnosed participants reporting injection drug use since 2017, and an important increase in the proportion of patients born in an HIV-endemic country (24%, 7/29 in 2019), especially among women. Compared to patients from non-endemic countries, those from HIV-endemic countries were characterized by higher proportions of heterosexuals (88% vs 17%) and of women (52% vs 7%), and were twice likely to get diagnosed at an advanced stage of HIV infection (32% vs 15%). In absolute numbers, MSM continue to account for the largest exposure category. However, patients from HIV-endemic countries, who tend to be diagnosed at later stages of HIV infection, constitute an increasing proportion of newly diagnosed individuals. These persons could face distinct barriers to rapid diagnosis. Tailoring HIV testing strategies and other prevention interventions to the specific unmet prevention needs of these individuals is warranted.

New HIV infections occur every year in Canada, highlighting the need for integrated prevention programs. Pre-exposure prophylaxis (PrEP) and nonoccupational postexposure prophylaxis (nPEP) are two important strategies for preventing HIV that should be considered standard of care and implemented as components of a comprehensive response to the epidemic. Pre-exposure prophylaxis is the use of certain antiretroviral medications by HIV-uninfected persons who are at high, ongoing risk of HIV acquisition, beginning before and continuing after potential HIV exposures. Postexposure prophylaxis (PEP) involves 28 days of antiretroviral medications immediately after a specific HIV exposure, and is nonoccupational when used after sexual and injection drug use exposures, rather than accidental exposures that occur in work contexts. The large financial cost of HIV infection and the young age of those newly diagnosed underscore the economic and social importance of preventing new infections. We hope that this guideline will contribute to reducing HIV incidence in Canada by improving the quality of care, increasing access to care, reducing inappropriate variation in practice and promoting the rigorous evaluation of biomedical prevention strategies nationwide.

There is limited evidence on the efficacy of post-exposure prophylaxis (PEP) for sexual exposures. We sought to determine the factors associated with adherence to treatment and describe the incidence of PEP failures in a Montreal clinic. We prospectively assessed all patients consulting for PEP following sexual exposures from October 2000 to July 2014. Patients were followed at 4 and 16 weeks after starting PEP. Treatment adherence was determined by self-report at week 4. Multivariable logistic regression was used to estimate the factors predicting adherence to treatment. 3547 PEP consults were included. Patients were mainly male (92%), MSM (83%) and sought PEP for anal intercourse (72%). Seventy-eight percent (n = 2772) of patients received a prescription for PEP, consisting of Tenofovir/Emtracitabine (TVD) + Lopinavir/Ritonavir (LPV) in 74% of cases, followed by Zidovudine/Lamivudine (CBV) + LPV (10%) and TVD + Raltegravir (RAL) (8%). Seventy percent of patients were adherent to treatment. Compared to TVD+LPV, patients taking CBV+LPV were less likely to adhere to treatment (OR 0.58, 95% CI 0.44-0.75), while no difference was observed for patients taking TVD+RAL (OR 1.15, 95% CI 0.83-1.59). First-time PEP consults, older and male patients were also more adherent to treatment. Ten treated patients seroconverted (0.37%) during the study period, yet only 1 case can be attributed to PEP failure (failure rate = 0.04%). PEP regimen was associated with treatment adherence. Patients were more likely to be adherent to TVD-based regimens. Ten patients seroconverted after taking PEP; however, only 1 case was a PEP failure as the remaining patients continued to engage in high-risk behavior during follow-up. One month PEP is an effective preventive measure to avoid HIV infection.

ObjectivesUse 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.MethodsWe 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.ResultsThere 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.ConclusionAmong 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.

Mild cognitive impairment is common in chronic HIV infection and there is concern that it may worsen with age. Distinguishing static impairment from on-going decline is clinically important, but the field lacks well-validated cognitive measures sensitive to decline and feasible for routine clinical use. Measures capable of detecting improvement are also needed to assess interventions. The objective of this study is to estimate the extent of change on repeat administration of three different forms of a brief computerized cognitive assessment battery (B-CAM) developed for assessing cognitive ability in the mildly-impaired to normal range in people living with HIV. We hypothesized no change over a six-month period in people on effective antiretroviral therapy. 102 HIV+ individuals completed a set of computerized cognitive tasks on three occasions over a six-month period. Rasch analysis was used to determine if change over time (i.e. improvement due to practice) was uniform across tasks and to refine scoring in order to produce three forms of the B-CAM of equivalent level of difficulty. Group-based trajectory analysis (GBTA) was then applied to determine if performance at baseline influenced the magnitude of practice-related improvement on the battery as a whole over the course of follow-up. Two cognitive tasks (fluency and word recall) had different levels of difficulty across test sessions, related to the different forms of the tasks. These two items were split by testing session. For all other items, the level of difficulty remained constant across all three time points. GBTA showed that the sample was composed of three distinct groups of people with unique trajectories, defined mainly by level of cognitive ability at baseline. Only the highest group showed an apparent improvement over time, but this change fell within measurement error. Rasch analysis provides mathematical confirmation that these three forms of the B-CAM are of equivalent difficulty. GBTA demonstrates that no adjustment of the total score is required to correct for practice effects. Application of these modern statistical methods paves the way towards rapid and robust quantification of change in cognition.

CXCL13 is preferentially secreted by Follicular Helper T cells (T ) to attract B cells to germinal centers. Plasma levels of CXCL13 have been reported to be elevated during chronic HIV-infection, however there is limited data on such elevation during early phases of infection and on the effect of ART. Moreover, the contribution of CXCL13 to disease progression and systemic immune activation have been partially defined. Herein, we assessed the relationship between plasma levels of CXCL13 and systemic immune activation. Study samples were collected in 114 people living with HIV (PLWH) who were in early (EHI) or chronic (CHI) HIV infection and 35 elite controllers (EC) compared to 17 uninfected controls (UC). A subgroup of 11 EHI who initiated ART and 14 who did not were followed prospectively. Plasma levels of CXCL13 were correlated with CD4 T cell count, CD4/CD8 ratio, plasma viral load (VL), markers of microbial translocation [LPS, sCD14, and (1→3)-β-D-Glucan], markers of B cell activation (total IgG, IgM, IgA, and IgG1-4), and inflammatory/activation markers like IL-6, IL-8, IL-1β, TNF-α, IDO-1 activity, and frequency of CD38 HLA-DR T cells on CD4 and CD8 T cells. Plasma levels of CXCL13 were elevated in EHI (127.9 ± 64.9 pg/mL) and CHI (229.4 ± 28.5 pg/mL) compared to EC (71.3 ± 20.11 pg/mL), and UC (33.4 ± 14.9 pg/mL). Longitudinal analysis demonstrated that CXCL13 remains significantly elevated after 14 months without ART ( < 0.001) and was reduced without normalization after 24 months on ART ( = 0.002). Correlations were observed with VL, CD4 T cell count, CD4/CD8 ratio, LPS, sCD14, (1→3)-β-D-Glucan, total IgG, TNF-α, Kynurenine/Tryptophan ratio, and frequency of CD38+HLA-DR+ CD4 and CD8 T cells. In addition, CMV+ PLWH presented with higher levels of plasma CXCL13 than CMV- PLWH ( = 0.005). Plasma CXCL13 levels increased with HIV disease progression. Early initiation of ART reduces plasma CXCL13 and B cell activation without normalization. CXCL13 represents a novel marker of systemic immune activation during early and chronic HIV infection and may be used to predict the development of non-AIDS events.

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.