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Buprenorphine is an effective treatment for opioid use disorder but can be slow when using a standard low-dose titration protocol to avoid precipitated withdrawal. This presents a substantial practical barrier in clinical practice. Recent low-dose induction strategies have attempted to simplify and shorten the process required for successful induction, including our own transdermal buprenorphine method, which achieves induction to sublingual buprenorphine/naloxone after 48 h. Here, we present two inpatients with active unregulated fentanyl use that were successfully initiated on buprenorphine extended-release with a novel 24-h transdermal buprenorphine protocol without precipitating withdrawal. This protocol may represent a substantial improvement in the practical feasibility of initiating buprenorphine for patients and providers, although further study is required to confirm efficacy and tolerability.

Background: Oral human papillomavirus (HPV) infections are a leading cause of oropharyngeal cancers. In 2015 and 2016, HPV vaccines became publicly funded for gay, bisexual, and other men who have sex with men (GBM) under 27 years of age in most Canadian provinces., Methods: Between 2017 and 2019, sexually active GBM in Montreal, Toronto, and Vancouver were recruited through respondent-driven sampling. Participants aged 16-30 years were invited to self-collect oral rinse specimens for HPV testing. We estimated HPV prevalence in the oral tract overall and compared these by vaccination status., Results: Among the 838 GBM with a valid oral specimen, 36.9% reported receiving ≥1 dose of HPV vaccine. Overall, oral HPV prevalence was 2.6% (95% confidence interval [CI], 1.5%-3.7%) for at least 1 HPV type and 1.2% (95% CI, .5%-1.9%) for any high-risk type. We detected quadrivalent (HPV 6/11/16/18) vaccine-preventable types in 0.3% (95% CI, .0%-1.0%) of vaccinated individuals and 1.1% (95% CI, .1%-2.0%) of unvaccinated individuals., Conclusions: Oral HPV prevalence was low in a population of young urban GBM in Canada, of whom 37% were vaccinated. Findings serve as a benchmark for monitoring of vaccination impacts on oral HPV infection within this priority population., Competing Interests: Potential conflicts of interest. D. H. S. T.'s institution has received investigator-initiated grants from Abbvie and Gilead; and support for participation in clinical trials sponsored by Glaxo Smith Kline. F. C. reports grants from Réseau FRQS-SIDA during the conduct of the study; and grants to his institution for HPV-related work from Merck Sharp and Dome, Roche Diagnostics, and Becton Dickinson, outside of the submitted work. A. D. P. reports grants from Réseau FRQS-SIDA during the conduct of the study. C. S. is a member of the HPV working group of the National Advisory Committee on Immunization; and is an active member of the Québec Immunization Committee. J. C.’s institution has received funding from ViiV Healthcare and Gilead for research; and J. C. has received remuneration for advisory work from ViiV Healthcare and Gilead. T. A. H. has received funds as Director of the HOPE Centre from Gilead, ViiV, and DECIEM. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background Pre-exposure prophylaxis (PrEP) use has been attributed to heightened rates of sexually transmitted infections (STIs), ostensibly due to increased condomless anal sex (CAS) and greater frequency of STI testing. Few qualitative studies have assessed how gay, bisexual and queer men (GBQM) who use PrEP perceive STIs and how these attitudes have evolved post-PrEP uptake. We investigated the perspectives of current and former PrEP users on STIs. Methods Annual, in-depth longitudinal interviews were conducted with 38 current and former PrEP users in Ontario (n =18) and British Columbia (n =20), Canada, as part of a mixed-methods implementation science study (2020-2022). Over 3years, 109 interviews were conducted. Data analysis included reflexive thematic coding and longitudinal recurrent cross-sectional analysis using NVivo 12. Results Four STI-related themes emerged: (1) lack of STI-related concerns due to treatment and prevention optimism, (2) stigma-related concerns, (3) perceived risk among other PrEP users due to increased CAS, and (4) inconsistent testing concerns among non-PrEP users. Over time, some STI-related anxieties decreased with increased knowledge and reduced stigma. However, concerns persisted for other participants due to perceived risky sexual behaviours among other PrEP users and non-PrEP users. Both current and former PrEP users who expressed STI-related apprehensions consistently indicated adopting risk-reduction strategies, including condom use and having fewer sexual partners throughout the study. Conclusions Findings show how varied STI perceptions and experiences among current and former PrEP users shaped sexual decision-making over time. Providers, public health experts, and policymakers should develop a more comprehensive strategy to address STI concerns among GBQM.

Background: Both HIV and hepatitis C virus (HCV) infection increase the risk of hepatic steatosis (HS), which in turn contributes to the severity and progression of liver disease. Direct acting antivirals (DAAs) can cure HCV but whether they reduce HS is unclear., Methods: HS was assessed using the controlled attenuation parameter (CAP) and the hepatic steatosis index (HSI) in participants coinfected with HIV-HCV from the Canadian Coinfection Cohort. Changes in HS, before, during and after successful DAA treatment, were estimated using generalized additive mixed models, adjusted for covariates measured prior to treatment (age, sex, duration of HCV infection, body mass index, diabetes, prior exposure to dideoxynucleosides and hazardous drinking)., Results: 431 participants with at least one measure of CAP or HSI before treatment were included. CAP steadily increased over time: adjusted annual slope 3.3 dB/m (95% credible interval (CrI) 1.6, 4.9) before, and 3.9 dB/m (95% CrI: 1.9, 5.9) after DAA treatment, irrespective of pre-treatment CAP. In contrast, HSI changed little over time: annual slope 0.2 (95% CrI: -0.1, 0.5) before and 0.2 (95% CrI -0.1, 0.5) after, but demonstrated a marked reduction during treatment -4.5 (95% CrI -5.9, -3.1)., Conclusions: When assessed by CAP, HS was unaffected by DAA treatment and steadily increased over time. In contrast, HSI did not appear to reflect changes in HS, with the decrease during treatment likely related to resolution of hepatic inflammation. Ongoing HS may pose a risk for liver disease in coinfected people cured of HCV., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Highly pathogenic avian influenza (HPAI) H5N1 has been associated with significant morbidity and mortality. Given recent detections of HPAI H5N1 in dairy cattle and RNA detections in pasteurized retail milk in the United States, we established the Pan-Canadian Milk Network in April 2024. Through this, retail milk was procured longitudinally and sent to a central laboratory to test for the presence of influenza A virus RNA. We tested 109 retail milk samples from all ten Canadian provinces and all samples tested negative. Our independent testing results have aligned with reporting from federal retail milk testing initiatives. Despite no known HPAI infections of dairy cattle in Canada to date, H5N1 poses a significant threat to the health of both humans and other animals. By performing routine surveillance of retail milk on a national scale, we have shown that academic networks and initiatives can rapidly establish nationwide emerging infectious disease surveillance that is cost-effective, standardized, scalable, and easily accessible. Our network can serve as an early detection system to help inform containment and mitigation activities if positive samples are identified and can be readily reactivated should H5N1 or other emerging zoonotic viruses be identified in agricultural or livestock settings.

Introduction: The COVID-19 pandemic has changed healthcare service delivery. We examined the overall impact of COVID-19 on people living with HIV in British Columbia (BC), Canada, with a special focus on the potential impact of COVID-19 on antiretroviral treatment interruptions (TIs)., Methods: Purposive sampling was used to enrol people living with HIV aged ≥19 years across BC into the STOP HIV/AIDS Program Evaluation study between January 2016 and September 2018. Participants completed surveys at baseline enrolment and 18 and 36 months later. Additional COVID-19 questions were added to the survey in October 2020. TIs were defined as >60 days late for antiretroviral therapy (ART) refill using data from the BC HIV Drug Treatment Program. Generalized linear mixed models were used to examine trends in TIs over time and associations with reported health service access., Results: Of 581 participants, 6.1%-7.7% experienced a TI during each 6-month period between March 2019 and August 2021. The frequency of TIs did not statistically increase during the COVID-19 epidemic. Among the 188 participants who completed the COVID-19 questionnaire, 32.8% reported difficulty accessing healthcare during COVID-19, 9.7% reported avoiding continuing a healthcare service due to COVID-19-related concerns, and 74.6% reported using virtual healthcare services since March 2020. In multivariable analysis, the odds of a TI in any 6-month period were not significantly different from March to August 2019. None of the reported challenges to healthcare services were associated with TIs., Conclusions: Although some participants reported challenges to accessing services or avoidance of services due to COVID-19, TIs were not more likely during COVID-19 than before., (© 2024 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: The United States has lost many lives to COVID-19. The role of social capital and collective action has been previously explored in the context of COVID-19. The current study specifically investigates the role of social trust at the county level and COVID-19 mortality in the US, hypothesizing that counties with higher social trust will have lower COVID-19 mortality rates., Methods: We used cross-sectional data from the General Social Survey (GSS). We collected COVID-19 mortality data from the COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University until October 31, 2021. We obtained county characteristics from the 2019 American Community Survey and supplemented this data source with additional publicly available county-level data, such as measures of income inequality and political leanings. We measured social trust as a single item from the GSS and calculated mean social trust in a county by pooling responses from 2002 to 2018. We then modeled the relationship between mean social trust and COVID-19 mortality., Results: Results indicate that counties with higher social trust have lower COVID-19 mortality rates. Higher values of mean social trust at the county level are associated with a decrease in COVID-19 mortality (b= -0.25, p-value < 0.001), after adjustment for confounding. The direction of association is consistent in a sensitivity analysis., Conclusions: Our findings underscore the importance of investment in social capital and social trust. We believe these findings can be applied beyond the COVID-19 pandemic, as they demonstrate the potential for social trust as a method for emergency preparedness., (© 2024. The Author(s).)

Background: People with HIV are at higher risk of infection-related cancers than the general population, which could be due, in part, to immune dysfunction. Our objective was to examine associations between 4 CD4 count measures as indicators of immune function and infection-related and infection-unrelated cancer risk., Setting: We conducted a cohort study of adults with HIV who were diagnosed with cancer in Ontario, Canada. Incident cancers were identified from January 1, 1997 to December 31, 2020., Methods: We estimated adjusted hazard ratios (aHR) for the associations between CD4 measures (baseline CD4, nadir CD4, time-updated CD4, time-updated CD4:CD8) and cancer incidence rates using competing risk analyses, adjusted for socio-demographic factors, history of hepatitis B or C infection, baseline viral load, smoking, and alcohol use., Results: Among 4771 people with HIV, contributing 59,111 person-years of observation, a total of 549 cancers were observed. Low baseline CD4 (<200 cells/µL) (aHR 2.08 [95% CI: 1.38 to 3.13], nadir (<200 cells/µL) (aHR 2.01 [95% CI: 1.49 to 2.71]), low time-updated CD4 (aHR 3.52 [95% CI: 2.36 to 5.24]) and time-updated CD4:CD8 ratio (<0.4) (aHR 2.02 [95% CI: 1.08 to 3.79]) were associated with an increased rate of infection-related cancer. No associations were observed for infection-unrelated cancers., Conclusions: Low CD4 counts and indices were associated with increased rates of infection-related cancers among people with HIV, irrespective of the CD4 measure used. Early diagnosis and linkage to care and high antiretroviral therapy uptake may lead to improved immune function and could add to cancer prevention strategies such as screening and vaccine uptake., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Tracy Jansen Cheney: advisory board work for Gilead; Pierre Giguere: speaking honoraria and/or advisory board work for ViiV, Gilead, Merck, Pfizer; Deborah Kelly: speaking honoraria and/or advisory board work for ViiV, Gilead, Moderna; Dominic Martel: speaking honoraria and/or advisory board work for AbbVie, Gilead, Paladin and Pfizer; Carley Pozniak: speaking honoraria and advisory board work for Viiv, Gilead, Merck; Linda Robinson: speaker/educational honoraria, ViiV, Gilead, Merck; Jonathan Smith: advisory board work for ViiV; Alice Tseng: speaking honoraria and/or advisory board work for ViiV, Gilead, Merck, Pfizer.

Background: In many jurisdictions, policies restrict access to Opioid Agonist Treatment (OAT) in correctional facilities. Receipt of OAT during incarceration is associated with reduced risk of fatal overdose after release but little is known about the effect on nonfatal overdose. This study aimed to examine the association between OAT use during incarceration and nonfatal overdose in the 30 days following release., Methods and Findings: Using linked administrative healthcare and corrections data for a random sample of 20% of residents of British Columbia, Canada we examined releases from provincial correctional facilities between January 1, 2015 -December 1, 2018, among adults (aged 18 or older at the time of release) with Opioid Use Disorder. We fit Andersen-Gill models to examine the association between receipt of OAT in custody and the hazard of nonfatal following release. We conducted secondary analyses to examine the association among people continuing treatment initiated prior to their arrest and people who initiated a new episode of OAT in custody separately. We also conducted sex-based subgroup analyses. In this study there were 4,738 releases of 1,535 people with Opioid Use Disorder. In adjusted analysis, receipt of OAT in custody was associated with a reduced hazard of nonfatal overdose (aHR 0.55, 95% CI 0.41, 0.74). This was found for prescriptions continued from community (aHR 0.49, 95%CI 0.36, 0.67) and for episodes of OAT initiated in custody (aHR 0.58, 95%CI 0.41, 0.82). The effect was greater among women than men., Conclusions: OAT receipt during incarceration is associated with a reduced hazard of nonfatal overdose after release. Policies to expand access to OAT in correctional facilities, including initiating treatment, may help reduce harms related to nonfatal overdose in the weeks following release. Differences in the effect seen among women and men indicate a need for gender-responsive policies and programming., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 McLeod et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The primary obstacle to curing HIV-1 is a reservoir of CD4+ cells that contain stably integrated provirus. Previous studies characterizing the proviral landscape, which have been predominantly conducted in males in the United States and Europe living with HIV-1 subtype B, have revealed that most proviruses that persist during antiretroviral therapy (ART) are defective. In contrast, less is known about proviral landscapes in females with non-B subtypes, which represents the largest group of individuals living with HIV-1. Here, we analyze genomic DNA from resting CD4+ T-cells from 16 female and seven male Ugandans with HIV-1 receiving suppressive ART (n = 23). We perform near-full-length proviral sequencing at limiting dilution to examine the proviral genetic landscape, yielding 607 HIV-1 subtype A1, D, and recombinant proviral sequences (mean 26/person). We observe that intact genomes are relatively rare and clonal expansion occurs in both intact and defective genomes. Our modification of the primers and probes of the Intact Proviral DNA Assay (IPDA), developed for subtype B, rescues intact provirus detection in Ugandan samples for which the original IPDA fails. This work will facilitate research on HIV-1 persistence and cure strategies in Africa, where the burden of HIV-1 is heaviest., (© 2024. The Author(s).)

Background: Treatment as prevention and pre-exposure prophylaxis (PrEP) are key strategies in the control of HIV/AIDS. We aimed to characterise the longitudinal effects of antiretroviral therapy (ART), followed by treatment as prevention and the addition of PrEP, on the HIV effective reproduction number (R e ) in British Columbia, Canada., Methods: This population-level programme evaluation used data from the Drug Treatment Program of the British Columbia Centre for Excellence in HIV/AIDS (Vancouver, British Columbia, Canada). We also used estimates of HIV incidence and prevalence from the Public Health Agency of Canada, data on the number of new HIV diagnoses per year from the British Columbia Centre for Disease Control, and mortality data from the British Columbia Vital Statistics Agency. Data were obtained from 1985 until 2022, depending on the database source. Outcomes were the annual HIV prevalence, HIV incidence, number of new HIV diagnoses, number of people living with HIV on ART, HIV/AIDS-related and all-cause mortality rates, the HIV incidence-to-all-cause-mortality ratio, and R e . We calculated the modified effective reproduction number (R me ) using two thresholds of viral suppression and compared these values with R e ., Findings: We found a 95% decline in HIV/AIDS-related mortality and a 91% decrease in HIV incidence over the study period. The R e progressively declined from 1996 to 2022; however, from 1996 to 2017, R me remained stable (>1) when calculated for people living with HIV with unsuppressed viraemia, suggesting that treatment as prevention reduces HIV incidence by decreasing the pool of individuals who are potentially able to transmit the virus. From 2018 to 2022, a decline in the estimated R e and R me (<1) was observed regardless of whether we considered all people living with HIV or only those who were virologically unsuppressed. This finding suggests that PrEP decreases HIV incidence by reducing the number of susceptible individuals in the community, independently of viral suppression., Interpretation: Our results show the synergy between generalised treatment as prevention and targeted PrEP in terms of decreasing HIV incidence. These findings support the incorporation of longitudinal monitoring of R e at a programmatic level to identify opportunities for the optimisation of treatment-as-prevention and PrEP programmes., Funding: British Columbia Ministry of Health, Health Canada, Public Health Agency of Canada, Vancouver Coastal Health, Vancouver General Hospital Foundation, Genome British Columbia, and the Canadian Institutes of Health Research., Competing Interests: Declaration of interests JSGM received institutional grants from Gilead Sciences, Merck, and ViiV Healthcare. VDL received honoraria to present at the 2023 Conference on Retroviruses and Opportunistic Infections ViiV Healthcare Ambassador Program. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Despite rural regions being disproportionately impacted by the toxic drug supply, little is known about the contextual factors influencing access to opioid agonist treatment (OAT) specific to rural residents. The present study examines these factors in a rural and coastal setting in British Columbia, Canada., Methods: The qualitative methods were used to examine the barriers and facilitators to OAT access. Between July and October 2021, semi-structured interviews were conducted with people who use drugs who reside in a rural and coastal community. Thematic analysis was used to identify emergent themes and subthemes. Results were corroborated by the research team and a local community advisory board., Results: Twenty-seven (n = 27) participants described both limiting and facilitating factors that influenced OAT accessibility. Access was less challenging when participants' OAT dispensing pharmacy was in close proximity, had extended hours of operation, or when pharmacies provided delivery services. Barriers to OAT access identified by participants included the high cost of transportation, residing or working in remote communities and few local OAT prescribers. A variety of treatment motivations and goals that impacted OAT satisfaction are also highlighted., Conclusion: This study demonstrates that patient satisfaction with OAT service access in a rural and coastal setting is multi-factorial and geographic proximity alone does not fully explain OAT accessibility issues in these settings. Accessibility to OAT may be improved through delivery services, expanded OAT prescribing authorisation beyond physician-only regulations, health authorities covering transportation costs and continual assurance that prescribing practices meet individuals' goals., Introduction: Bien que les régions rurales soient touchées de manière disproportionnée par l'approvisionnement en drogues toxiques, on sait peu de choses sur les facteurs contextuels qui influencent l'accès au traitement par agoniste opioïde (TAO) spécifique aux résidents ruraux. La présente étude examine ces facteurs dans un contexte rural et côtier en Colombie-Britannique, au Canada., Mthodes: Des méthodes qualitatives ont été utilisées pour examiner les obstacles et les facilitateurs de l'accès aux TAO. Entre juillet et octobre 2021, des entretiens semi-structurés ont été menés avec des personnes qui consomment des drogues résidant dans une communauté rurale et côtière. L'analyse thématique a été utilisée pour identifier les thèmes et sous-thèmes émergents. Les résultats ont été corroborés par l'équipe de recherche et un comité consultatif communautaire local., Rsultats: Vingt-sept (n = 27) participants ont décrit les facteurs limitants et facilitants qui ont influé sur l'accessibilité au TAO. L'accès était moins difficile lorsque la pharmacie du TAO des participants était proche, avait des heures d'ouverture prolongées ou lorsque les pharmacies offraient des services de livraison. Parmi les obstacles à l'accès au TAO mentionnés par les participants, il y avait le coût élevé du transport, le fait de résider ou de travailler dans des collectivités éloignées et la rareté des prescripteurs locaux du TAO. Les participants ont également fait état de divers objectifs et motivations liés au traitement qui ont eu une incidence sur la satisfaction à l'égard du TAO., Conclusion: Cette étude démontre que la satisfaction des patients à l'égard de l'accès aux services du TAO en milieu rural et côtier est multifactorielle et que la proximité géographique n'explique pas à elle seule les problèmes d'accessibilité au TAO dans ces milieux. Cette accessibilité peut être améliorée par des services de livraison, l'élargissement de l'autorisation de prescrire un TAO au-delà des règlements réservés aux médecins, la prise en charge des coûts de transport par les autorités sanitaires et l'assurance continue que les pratiques de prescription répondent aux objectifs des individus., (Copyright © 2024 Copyright: © 2024 Society of Rural Physicians of Canada.)

Objective: The immunogenic nature of coronavirus disease 2019 (COVID-19) mRNA vaccines led to some initial concern that these could stimulate the HIV reservoir. We analyzed changes in plasma HIV loads (pVL) and reservoir size following COVID-19 mRNA vaccination in 62 people with HIV (PWH) receiving antiretroviral therapy (ART), and analyzed province-wide trends in pVL before and after the mass vaccination campaign., Design: Longitudinal observational cohort and province-wide analysis., Methods: Sixty-two participants were sampled prevaccination, and one month after their first and second COVID-19 immunizations. Vaccine-induced anti-SARS-CoV-2-Spike antibodies in serum were measured using the Roche Elecsys Anti-S assay. HIV reservoirs were quantified using the intact proviral DNA assay; pVL were measured using the cobas 6800 (lower limit of quantification: 20 copies/ml). The province-wide analysis included all 290 401 pVL performed in British Columbia, Canada between 2012 and 2022., Results: Prevaccination, the median intact reservoir size was 77 [interquartile range (IQR): 20-204] HIV copies/million CD4 + T-cells, compared to 74 (IQR: 27-212) and 65 (IQR: 22-174) postfirst and -second dose, respectively (all comparisons P > 0.07). Prevaccination, 82% of participants had pVL <20 copies/ml (max: 110 copies/ml), compared to 79% postfirst dose (max: 183 copies/ml) and 85% postsecond dose (max: 79 copies/ml) ( P  > 0.4). There was no evidence that the magnitude of the vaccine-elicited anti-SARS-CoV-2-Spike immune response influenced pVL nor changes in reservoir size ( P  > 0.6). We found no evidence linking the COVID-19 mass vaccination campaign to population-level increases in detectable pVL frequency among all PWH in the province, nor among those who maintained pVL suppression on ART., Conclusion: We found no evidence that COVID-19 mRNA vaccines induced changes in HIV reservoir size nor plasma viremia., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The HIV program in Newfoundland and Labrador (NL) provides care for all persons living with HIV (PLWH) in NL, yet progress toward UNAIDS 95-95-95 goals for diagnosis, linkage to care and viral suppression has not previously been documented. This analysis describes engagement in HIV care and virologic outcomes for the NL cohort in 2016 and 2019 and compares this data to the Canadian HIV Observational Cohort (CANOC). A retrospective review of the NL clinic included adults aged >18 years and descriptive statistics for demographics, risk factors, and clinical variables were assessed and compared using χ2 test or Fisher's Exact test (categorical) or Wilcoxon Sum Rank test (continuous). Engagement in care and virologic outcomes for the NL cohort were consistently high over the 2016 to 2019 period with > 98% on antiretroviral therapy (ART), and > 96% having a suppressed virus load. Engagement in care and virologic outcomes among PLWH in NL is high and compares favorably to a national cohort., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Holder et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. We investigated whether bronchoalveolar lavage (BAL) cells of people living with HIV (PLWH) demonstrate epigenetic disruptions and advanced epigenetic aging., Methods: BAL cell DNA methylation from 25 PLWH and 16 HIV-uninfected individuals were tested for differential methylation of Alu and LINE-1 sites, markers of aging. We used a weighted gene correlation network analysis to identify HIV- and age-associated co-methylation networks. We tested the effect of HIV on DNA methylation using a robust linear model (false discovery rate < 0.10)., Results: The BAL cells of PLWH were marked by global hypomethylation in both Alu and LINE-1 elements. Six co-methylated CpG networks were identified that were significantly associated with age; of these, the red module was significantly differentially methylated in PLWH and enriched pathways (e.g., Ras signaling and T-cell receptors). We identified 6428 CpG sites associated with HIV., Conclusions: We have shown here for the first time that alterations in the DNA methylation of BAL cells in the lung with HIV show a pattern of advanced aging. This study strongly supports that HIV may contribute to an increased the risk of lung comorbidities through the epigenetics of aging.

The SARS-CoV-2 (COVID-19) pandemic has impacted the care of people living with HIV (PLWH). This study aims to characterize the impact of the pandemic on the length of HIV treatment gap lengths and viral loads among people living with HIV (PLWH) in British Columbia (BC), Canada, with a focus on Downtown Eastside (DTES), which is one of the most impoverished neighbourhoods in Canada. We analyzed data from the HIV/AIDS Drug Treatment Program from January 2019 to February 2022. The study had three phases: Pre-COVID, Early-COVID, and Late-COVID. We compared results for individuals residing in DTES, those not residing in DTES, and those with no fixed address. Treatment gap lengths and viral loads were analyzed using a zero-inflated negative binomial model and a two-part model, respectively, adjusting for demographic factors. Among the 8982 individuals, 93% were non-DTES residents, 6% were DTES residents, and 1% had no fixed address during each phase. DTES residents were more likely to be female, with Indigenous Ancestry, and have a history of injection drug use. Initially, the mean number of viral load measurements decreased for all PLWH during the Early-COVID, then remained constant. Treatment gap lengths increased for all three groups during Early-COVID. However, by Late-COVID, those with no fixed address approached pre-COVID levels, while the other two groups did not reach Early-COVID levels. Viral loads improved across each phase from Pre- to Early- to Late-COVID among people residing and not residing in DTES, while those with no fixed address experienced consistently worsening levels. Despite pandemic disruptions, both DTES and non-DTES areas enhanced HIV control, whereas individuals with no fixed address encountered challenges. This study offers insights into healthcare system preparedness for delivering HIV care during future pandemics, emphasizing community-driven interventions with a particular consideration of housing stability., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

HIV-1 group M (HIV-1M) lineages downregulate HLA-I and CD4 expression via their Nef proteins. We hypothesized that these Nef functions may be partially responsible for the differences in prevalence of viruses from different lineages that co-circulate within an epidemic. Here, we characterized these two Nef activities in HIV-1M isolates from Cameroon, where multiple variants have been circulating since the pandemic's origin. Single HIV-1 Nef clones from 234 HIV-1-ART naïve individuals living in remote villages and two cosmopolitan cities of Cameroon, sampled between 2000 and 2013, were isolated from plasma HIV RNA and analyzed for their capacity to downregulate HLA-I and CD4 molecules. We found that, despite a large degree of within- and inter- lineage variation, the ability of Nef to downregulate HLA-I was similar across these different viruses. Moreover, Nef-mediated CD4 downregulation activity was also well conserved across the different lineages found in Cameroon. In addition, we observed a trend towards higher HLA-I downregulation activity of viruses circulating in the cosmopolitan cities versus the remote villages, whereas the CD4 downregulation activities were similar across the two settings. Furthermore, we noted a significant decline of HLA-I downregulation activity from 2000 to 2013, providing additional evidence supporting the attenuation of the global HIV-1M population over time. Finally, we identified 18 amino acids associated with differential HLA-I downregulation and 13 amino acids associated with differential CD4 downregulation within the dominant CRF02&#95;AG lineage. Our lack of observation of HIV lineage-related differences in Nef-mediated HLA-I and CD4 downregulation function suggests that these activities do not substantively influence the prevalence of different HIV-1M lineages in Cameroon., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

People living with HIV (PLWH) can exhibit impaired immune responses to vaccines. Accumulating evidence indicates that PLWH, particularly those receiving antiretroviral therapy, mount strong antibody responses to COVID-19 vaccines, but fewer studies have examined cellular immune responses to the vaccinations. Here, we used an activation-induced marker (AIM) assay to quantify SARS-CoV-2 spike-specific CD4+ and CD8+ T cells generated by two and three doses of COVID-19 vaccines in 50 PLWH receiving antiretroviral therapy, compared to 87 control participants without HIV. In a subset of PLWH, T-cell responses were also assessed after post-vaccine breakthrough infections and/or receipt of a fourth vaccine dose. All participants remained SARS-CoV-2 infection-naive until at least one month after their third vaccine dose. SARS-CoV-2 infection was determined by seroconversion to a Nucleocapsid (N) antigen, which occurred in 21 PLWH and 38 control participants after the third vaccine dose. Multivariable regression analyses were used to investigate the relationships between sociodemographic, health- and vaccine-related variables, vaccine-induced T-cell responses, and breakthrough infection risk. We observed that a third vaccine dose boosted spike-specific CD4+ and CD8+ T-cell frequencies significantly above those measured after the second dose (all p < 0.0001). Median T-cell frequencies did not differ between PLWH and controls after the second dose ( p > 0.1), but CD8+ T-cell responses were modestly lower in PLWH after the third dose ( p = 0.02), an observation that remained significant after adjusting for sociodemographic, health- and vaccine-related variables ( p = 0.045). In PLWH who experienced a breakthrough infection, median T-cell frequencies increased even higher than those observed after three vaccine doses ( p < 0.03), and CD8+ T-cell responses in this group remained higher even after a fourth vaccine dose ( p = 0.03). In multivariable analyses, the only factor associated with an increased breakthrough infection risk was younger age, which is consistent with the rapid increase in SARS-CoV-2 seropositivity that was seen among younger adults in Canada after the initial appearance of the Omicron variant. These results indicate that PLWH receiving antiretroviral therapy mount strong T-cell responses to COVID-19 vaccines that can be enhanced by booster doses or breakthrough infection.

COVID-19 breakthrough infection (BTI) can occur despite vaccination. Using a multi-centre, prospective, observational Canadian cohort of people with HIV (PWH) receiving ≥2 COVID-19 vaccines, we compared the SARS-CoV-2 spike (S) and receptor-binding domain (RBD)-specific IgG levels 3 and 6 months post second dose, as well as 1 month post third dose, in PWH with and without BTI. BTI was defined as positivity based on self-report measures (data up to last study visit) or IgG data (up to 1 month post dose 3). The self-report measures were based on their symptoms and either a positive PCR or rapid antigen test. The analysis was restricted to persons without previous COVID-19 infection. Persons without BTI remained COVID-19-naïve until ≥3 months following the third dose. Of 289 participants, 92 developed BTI (31.5 infections per 100 person-years). The median days between last vaccination and BTI was 128 (IQR 67, 176), with the most cases occurring between the third and fourth dose (n = 59), corresponding to the Omicron wave. In analyses adjusted for age, sex, race, multimorbidity, hypertension, chronic kidney disease, diabetes and obesity, a lower IgG S/RBD (log10 BAU/mL) at 1 month post dose 3 was significantly associated with BTI, suggesting that a lower IgG level at this time point may predict BTI in this cohort of PWH.

Background: Hepatitis C virus (HCV) is a major health threat in Canada. In British Columbia (BC) province, 1.6% of the population had been exposed to HCV by 2012. Prevalence and incidence of HCV are very high in populations of people who use drugs (PWUD) and sex workers (SW), who may experience unique barriers to healthcare. Consequently, they are less likely to be treated for HCV. Overcoming these barriers is critical for HCV elimination. This research sought to explore the healthcare experiences of PWUD and SW and how these experiences impact their willingness to engage in healthcare in the future, including HCV care., Methods: Interpretive Description guided this qualitative study of healthcare experiences in BC, underpinned by the Health Stigma and Discrimination framework. The study team included people with living/lived experience of drug use, sex work, and HCV. Twenty-five participants completed in-depth semi-structured interviews on their previous healthcare and HCV-related experiences. Thematic analysis was used to identify common themes., Results: Three major themes were identified in our analysis. First, participants reported common experiences of delay and refusal of care by healthcare providers, with many negative healthcare encounters perceived as rooted in institutional culture reflecting societal stigma. Second, participants discussed their choice to engage in or avoid healthcare. Many avoided all but emergency care following negative experiences in any kind of healthcare. Third, participants described the roles of respect, stigma, dignity, fear, and trust in communication in healthcare relationships., Conclusions: Healthcare experiences shared by participants pointed to ways that better understanding and communication by healthcare providers could support positive change in healthcare encounters of PWUD and SW, who are at high risk of HCV infection. More positive healthcare encounters could lead to increased healthcare engagement which is essential for HCV elimination., (© 2024. The Author(s).)

Background: Men who have sex with men (MSM) in British Columbia (BC) are disproportionately affected by infectious syphilis and HIV. In this study, we developed a co-interaction model and evaluated the impact and effectiveness of possible interventions among different MSM subgroups on the syphilis epidemic., Methods: We designed a deterministic compartmental model, which stratified MSM by HIV status and HIV pre-exposure prophylaxis (HIV-PrEP) usage into (1) HIV-negative/unaware MSM (HIV-PrEP not recommended, not on HIV-PrEP), (2) HIV-negative/unaware MSM with HIV-PrEP recommended (not on HIV-PrEP), (3) HIV-negative/unaware MSM actively on HIV-PrEP, and (4) MSM diagnosed with HIV. We estimated the effect of scaling up syphilis testing frequency from Status Quo to six-, four-, and three-months, increasing the percentage of MSM using doxycycline prevention (Doxy-P) to 25%, 50%, and 100% of the target level, and a combination of both among subgroups (2)-(4). We also assessed the impact of these interventions on the syphilis incidence rates from 2020 to 2034 in comparison to the Status Quo scenario where no intervention was introduced., Findings: Under the Status Quo scenario, with the expansion of the HIV-PrEP program to improve syphilis testing, the syphilis incidence rate was estimated to peak at 16.1 [Credible Interval (CI):14.2-17.9] per 1,000 person-years (PYs) in 2023 and decrease to 6.7 (CI:3.8-10.9) per 1,000 PYs by 2034. The syphilis incidence rate in 2034 was estimated at 0.7 (0.3-1.3) per 1,000 PYs if MSM diagnosed with HIV could be tested every four months, and at 1.5 (0.7-3.0) per 1,000 PYs if HIV-negative/unaware MSM actively on HIV-PrEP could be tested every three months. By achieving 100% of the target coverage of Doxy-P, the syphilis incidence rate was estimated at 1.4 (0.5-3.4) if focusing on MSM diagnosed with HIV, and 2.6 (1.2-5.1) per 1,000 PYs if focusing on HIV-negative/unaware MSM actively on HIV-PrEP. Under the combined interventions, the syphilis incidence rate could be as low as 0.0 (0.0-0.1) and 0.8 (0.3-1.8) per 1,000 PYs, respectively., Interpretation: The HIV-PrEP program in BC plays a crucial role in increasing syphilis testing frequency among high-risk MSM and reducing syphilis transmission among this group. In addition, introducing Doxy-P can be an effective complementary strategy to minimize syphilis incidence, especially among MSM diagnosed with HIV., Funding: This work was funded by the Canadian Institutes of Health Research., Competing Interests: JSGM is the Executive Director and Physician-in-Chief of the BC Centre for Excellence in HIV/AIDS, a provincial program serving all BC health authorities and based at St. Paul’s Hospital-Providence Health Care. JSGM’s Treatment as Prevention® (TasP®) research, paid to his institution, has received support from the BC Ministry of Health, Health Canada, Canadian Institutes of Health Research, Public Health Agency of Canada, Genome Canada, Genome BC, Vancouver Coastal Health, and Vancouver General Hospital Foundation. Institutional grants have been provided by Gilead, Merck, and ViiV Healthcare. VDL received honoraria to present at the 2023 CROI (Conference on Retroviruses and Opportunistic Infections) ViiV Healthcare Ambassador Program. JS is supported by a Canadian HIV Trials Network postdoctoral fellowship award and a Michael Smith Foundation for Health Research trainee award. MH has received research funding for an investigator-initiated study from Gilead Life Sciences and Merck. MH has also received honoraria for advisory boards, and speaking engagements paid to his institution. TG’s institution has received investigator-initiated research grants from Gilead and Merck. The other authors declare that they have no competing interests., (© 2024 The Author(s).)

Objectives: The community-based, longitudinal, Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) explored the experiences of women with HIV in Canada over the past decade. CHIWOS' high-impact publications document significant gaps in the provision of healthcare to women with HIV. We used concept mapping to analyse and present a summary of CHIWOS findings on women's experiences navigating these gaps., Design: Concept mapping procedures were performed in two steps between June 2019 and March 2021. First, two reviewers (AY and PM) independently reviewed CHIWOS manuscripts and conference abstracts written before 1 August 2019 to identify main themes and generate individual concept maps. Next, the preliminary results were presented to national experts, including women with HIV, to consolidate findings into visuals summarising the experiences and care gaps of women with HIV in CHIWOS., Setting: British Columbia, Ontario and Quebec, Canada., Participants: A total of 18 individual CHIWOS team members participated in this study including six lead investigators of CHIWOS and 12 community researchers., Results: Overall, a total of 60 peer-reviewed manuscripts and conference abstracts met the inclusion criteria. Using concept mapping, themes were generated and structured through online meetings. In total, six composite concept maps were co-developed: quality of life, HIV care, psychosocial and mental health, sexual health, reproductive health, and trans women's health. Two summary diagrams were created encompassing the concept map themes, one for all women and one specific to trans women with HIV. Through our analysis, resilience, social support, positive healthy actions and women-centred HIV care were highlighted as strengths leading to well-being for women with HIV., Conclusions: Concept mapping resulted in a composite summary of 60 peer-reviewed CHIWOS publications. This activity allows for priority setting to optimise care and well-being for women with HIV., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: People living with hepatitis C infection (HCV) have a significant impact on the global healthcare system, with high rates of inpatient service use. Direct-acting antivirals (DAAs) have the potential to alleviate this burden; however, the evidence on the impact of HCV infection and hospital outcomes is undetermined. This systematic review aims to assess this research gap, including how DAAs may modify the relationship between HCV infection and hospital-related outcomes., Methods: We searched five databases up to August 2022 to identify relevant studies evaluating the impact of HCV infection on hospital-related outcomes. We created an electronic database of potentially eligible articles, removed duplicates, and then independently screened titles, abstracts, and full-text articles., Results: A total of 57 studies were included. Analysis of the included studies found an association between HCV infection and increased number of hospitalizations, length of stay, and readmissions. There was less consistent evidence of a relationship between HCV and in-hospital mortality. Only four studies examined the impact of DAAs, which showed that DAAs were associated with a reduction in hospitalizations and mortality. In the 14 studies available among people living with HIV, HCV coinfection similarly increased hospitalization, but there was less evidence for the other hospital-related outcomes., Conclusions: There is good to high-quality evidence that HCV negatively impacts hospital-related outcomes, primarily through increased hospitalizations, length of stay, and readmissions. Given the paucity of studies on the effect of DAAs on hospital outcomes, future research is needed to understand their impact on hospital-related outcomes., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2024 Michelle Ng et al.)

Current antiretroviral therapy for HIV-1 infection does not represent a cure for infection as viral rebound inevitably occurs following discontinuation of treatment. The "block and lock" therapeutic strategy is intended to enforce proviral latency and durably suppress viremic reemergence in the absence of other intervention. The transcription-associated cyclin-dependent protein kinases (tCDKs) are required for expression from the 5´ HIV-1 long-terminal repeat, but the therapeutic potential of inhibiting these kinases for enforcing HIV-1 latency has not been characterized. Here, we expanded previous observations to directly compare the effect of highly selective small molecule inhibitors of CDK7 (YKL-5-124), CDK9 (LDC000067), and CDK8/19 (Senexin A), and found each of these prevented HIV-1 provirus expression at concentrations that did not cause cell toxicity. Inhibition of CDK7 caused cell cycle arrest, whereas CDK9 and CDK8/19 inhibitors did not, and could be continuously administered to establish proviral latency. Upon discontinuation of drug administration, HIV immediately rebounded in cells that had been treated with the CDK9 inhibitor, while proviral latency persisted for several days in cells that had been treated with CDK8/19 inhibitors. These results identify the mediator kinases CDK8/CDK19 as potential "block and lock" targets for therapeutic suppression of HIV-1 provirus expression., Competing Interests: The authors declare no conflict of interest.

Aims: To cope with homonegativity-generated stress, gay, bisexual and other men who have sex with men (GBM) use more mental health services (MHS) compared with heterosexual men. Most previous research on MHS among GBM uses data from largely white HIV-negative samples. Using an intersectionality-based approach, we evaluated the concomitant impact of racialization and HIV stigma on MHS use among GBM, through the mediating role of perceived discrimination (PD)., Methods: We used baseline data from 2371 GBM enrolled in the Engage cohort study, collected between 2017 and 2019, in Montreal, Toronto and Vancouver, using respondent-driven sampling. The exposure was GBM groups: Group 1 ( n = 1376): white HIV-negative; Group 2 ( n = 327): white living with HIV; Group 3 ( n = 577): racialized as non-white HIV-negative; Group 4 ( n = 91): racialized as non-white living with HIV. The mediator was interpersonal PD scores measured using the Everyday Discrimination Scale (5-item version). The outcome was MHS use (yes/no) in the prior 6 months. We fit a three-way decomposition of causal mediation effects utilizing the imputation method for natural effect models. We obtained odds ratios (ORs) for pure direct effect (PDE, unmediated effect), pure indirect effect (PIE, mediated effect), mediated interaction effect (MIE, effect due to interaction between the exposure and mediator) and total effect (TE, overall effect). Analyses controlled for age, chronic mental health condition, Canadian citizenship, being cisgender and city of enrolment., Results: Mean PD scores were highest for racialized HIV-negative GBM (10.3, SD: 5.0) and lowest for white HIV-negative GBM (8.4, SD: 3.9). MHS use was highest in white GBM living with HIV (GBMHIV) (40.4%) and lowest in racialized HIV-negative GBM (26.9%). Compared with white HIV-negative GBM, white GBMHIV had higher TE (OR: 1.71; 95% CI: 1.27, 2.29) and PDE (OR: 1.68; 95% CI: 1.27, 2.24), and racialized HIV-negative GBM had higher PIE (OR: 1.09; 95% CI: 1.02, 1.17). Effects for racialized GBMHIV did not significantly differ from those of white HIV-negative GBM. MIEs across all groups were comparable., Conclusions: Higher MHS use was observed among white GBMHIV compared with white HIV-negative GBM. PD positively mediated MHS use only among racialized HIV-negative GBM. MHS may need to take into account the intersecting impact of homonegativity, racism and HIV stigma on the mental health of GBM.

Objective: There has been interest in a possible negative association between HIV and multiple sclerosis (MS). We aimed to compare the risk of MS in a cohort of individuals living with HIV to that in the general population., Methods: Population-based health data were accessed for 2 cohorts of HIV-positive persons from Sweden and British Columbia, Canada. Incident MS was identified using MS registries or a validated algorithm applied to administrative data. Individuals with HIV were followed from 1 year after the first clinical evidence of HIV or the first date of complete administrative health data (Canada = April 1, 1992 and Sweden = January 1, 2001) until the earliest of incident MS, emigration, death, or study end (Canada = March 31, 2020 and Sweden = December 31, 2018). The observed MS incidence rate in the HIV-positive cohort was compared to the expected age-, sex-, calendar year-, income-specific, and region of birth-specific rates in a randomly selected sample of >20% of each general population. The standardized incidence ratio (SIR) for MS following the first antiretroviral therapy exposure ("ART-exposed") was also calculated., Results: The combined Sweden-Canada cohort included 29,163 (75% men) HIV-positive persons. During 242,248 person-years of follow-up, 14 incident MS cases were observed in the HIV-positive cohort, whereas 26.19 cases were expected. The SIR for MS in the HIV-positive population was 0.53 (95% confidence interval [CI] = 0.32-0.90). The SIR for MS following the first ART exposure was 0.55 (95% CI = 0.31-0.96)., Interpretation: This international population-based study demonstrated a lower risk of MS among HIV-positive individuals, and HIV-positive ART-exposed individuals. These findings provide support for further exploration into the relationship among HIV, ART, and MS. ANN NEUROL 2024;95:487-494., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Within-host HIV populations continually diversify during untreated infection, and this diversity persists within infected cell reservoirs during antiretroviral therapy (ART). Achieving a better understanding of on-ART proviral evolutionary dynamics, and a better appreciation of how the overall persisting pool of (largely genetically defective) proviruses differs from the much smaller replication-competent HIV reservoir, is critical to HIV cure efforts. We reconstructed within-host HIV evolutionary histories in blood from seven participants of the Women's Interagency HIV Study who experienced HIV seroconversion, and used these data to characterize the diversity, lineage origins, and ages of proviral env-gp120 sequences sampled longitudinally up to 12 years on ART. We also studied HIV sequences emerging from the reservoir in two participants. We observed that proviral clonality generally increased over time on ART, with clones frequently persisting long term. While on-ART proviral integration dates generally spanned the duration of untreated infection, HIV emerging in plasma was exclusively younger (i.e., dated to the years immediately pre-ART). The genetic and age distributions of distinct proviral sequences remained stable during ART in all but one participant, in whom there was evidence that younger proviruses had been preferentially eliminated after 12 years on ART. Analysis of the gag region in three participants corroborated our env-gp120 -based observations, indicating that our observations are not influenced by the HIV region studied. Our results underscore the remarkable genetic stability of the distinct proviral sequences that persist in blood during ART. Our results also suggest that the replication-competent HIV reservoir is a genetically restricted, younger subset of this overall proviral pool.IMPORTANCECharacterizing the genetically diverse HIV sequences that persist in the reservoir despite antiretroviral therapy (ART) is critical to cure efforts. Our observations confirm that proviruses persisting in blood on ART, which are largely genetically defective, broadly reflect the extent of within-host HIV evolution pre-ART. Moreover, on-ART clonal expansion is not appreciably accompanied by the loss of distinct proviral lineages. In fact, on-ART proviral genetic composition remained stable in all but one participant, in whom, after 12 years on ART, proviruses dating to around near ART initiation had been preferentially eliminated. We also identified recombinant proviruses between parental sequence fragments of different ages. Though rare, such sequences suggest that reservoir cells can be superinfected with HIV from another infection era. Overall, our finding that the replication-competent reservoir in blood is a genetically restricted, younger subset of all persisting proviruses suggests that HIV cure strategies will need to eliminate a reservoir that differs in key respects from the overall proviral pool., Competing Interests: The authors declare no conflict of interest.

There is mixed evidence on whether experiences of HIV-related stigma are mitigated with lived experience. We sought to examine whether people living with HIV (PLWH) with longer living experience reported varying levels of HIV-related stigma. Between January 2016-September 2018, we used purposive sampling to enrol PLWH aged ≥19 across British Columbia, Canada, where participants completed the 10-item Berger HIV Stigma Scale. We conducted bivariate analyzes examining key sociodemographic characteristics and HIV-related stigma scores. Multivariable linear regression modelled the association between year of HIV diagnosis by treatment era and HIV-related stigma scores. We enrolled 644 participants; median age at enrolment was 50 years (Q1-Q3: 42-56), with 37.4% ( n  = 241) diagnosed before the year 2000. The median HIV-stigma scores of all participants (19.0, Q1-Q3: 13-25, range 0-40) stratified by treatment era were: 17.0 (pre-1996), 20.0 (1996-1999), 20.0 (2000-2009), 19.0 (2010-2018) ( p  = 0.03). While there was a significant association at the univariate level, year of HIV diagnosis by treatment era was not associated with stigma scores after controlling for age, gender, HIV key populations, ethnicity, relationship status, social support, and ever having a mental health disorder diagnosis. This suggests that PLWH still experience HIV-related stigma today, compared to those diagnosed in earlier time periods.

We sought to characterize overdose and non-overdose mortality among PLWH amidst the illicit drug toxicity crisis in British Columbia, Canada. A population-based analysis of PLWH (age ≥19) in British Columbia accessing healthcare from April 1996 to March 2017 was conducted using data from the Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort linkage. Underlying causes of deaths were stratified into overdose and non-overdose causes. We compared (bivariate analysis) health-related characteristics and prescription history between PLWH died of overdose and non-overdose causes between April 2009 and March 2017. Among 9,180 PLWH, we observed 962 deaths (142 [14.7%] overdoses; 820 [85.2%] other causes). Compared to those who died from other causes, those who died of overdose were significantly younger (median age [Q, Q3]: 46 years [42, 52] vs. 54 years [48, 63]); had an indication of chronic pain (35.9% vs. 27.1%) and hepatitis C virus (64.8% vs. 50.4%), but fewer experienced hospitalization in the year before death. PLWH who died were most likely to be prescribed with opioids (>50%) and least likely with opioid agonist therapy (<10%) in a year before death. These findings highlight the syndemic of substance use, HCV, and chronic pain, and how the crisis is unqiuely impacting females and younger people.

Background: Estimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030., Methods and Findings: Using the PEARL model-an agent-based simulation of PWH who have initiated ART in the US-the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information). In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19% heterosexual women. Additionally, 44% were Black/AA, 32% White, and 23% Hispanic. Along with a gradual rise in population size of PWH receiving ART-reaching 908,000 individuals by 2030-PEARL forecasted a surge in prevalence of most comorbidities to 2030. Depression and/or anxiety was high and increased from 60% in 2020 to 64% in 2030. Hypertension decreased while dyslipidemia, diabetes, CKD, and MI increased. There was little change in prevalence of cancer and ESLD. The forecasted multimorbidity among PWH receiving ART increased from 63% in 2020 to 70% in 2030. There was heterogeneity in trends across subgroups. Among Black women with history of injection drug use in 2030 (oldest demographic subgroup with median age of 66 year), dyslipidemia, CKD, hypertension, diabetes, anxiety, and depression were most prevalent, with 92% experiencing multimorbidity. Among Black MSM in 2030 (youngest demographic subgroup with median age of 42 year), depression and CKD were highly prevalent, with 57% experiencing multimorbidity. These results are limited by the assumption that trends in new HIV diagnoses, mortality, and comorbidity risk observed in 2009 to 2017 will persist through 2030; influences occurring outside this period are not accounted for in the forecasts., Conclusions: The PEARL forecasts suggest a continued rise in comorbidity and multimorbidity prevalence to 2030, marked by heterogeneities across race/ethnicity, gender, and HIV acquisition risk subgroups. HIV clinicians must stay current on the ever-changing comorbidities-specific guidelines to provide guideline-recommended care. HIV clinical directors should ensure linkages to subspecialty care within the clinic or by referral. HIV policy decision-makers must allocate resources and support extended clinical capacity to meet the healthcare needs of people aging with HIV., Competing Interests: KNA serves on the scientific review board for TrioHealth Inc and as a consultant to the All of Us Research Program. MJG has been an Hoc member on national HIV Advisory Boards of Merck, Gilead and ViiV. CW is currently employed by Regeneron Pharmaceuticals Inc and contributed to this article as a prior trainee of Johns Hopkins University. KG declares that his institution receives funding from U.S. Department of Defense’s (DOD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), in collaboration with the Defense Health Agency (DHA) (contract number: W911QY2090012), Bloomberg Philanthropies, State of Maryland, NIH National Center for Advancing Translational Sciences (NCATS) U24TR001609, Division of Intramural Research NIAID NIH, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation for her work. KG received royalties from UptoDate and served as a paid consultant to Aspen Institute, and Teach for America. KG declares that none of these funding sources are related to this manuscript. PFR declares consultation with Gilead & Janssen pharmaceuticals (money paid to individual); research grants from NIH/NIAID (money paid to institution). JT declares to be consultant for AbbVie, Canfield, Gilead, Roche and Tarsier and being Equity owner for Tarsier. VFM has received support from the Emory CFAR (P30 AI050409) and received investigator-initiated research grants (to the institution) and consultation fees (both unrelated to the current work) from Eli Lilly, Bayer, Gilead Sciences, and ViiV. HNK declares that Gilead Sciences program funding paid to the author’s institution. The following authors have declared that no competing interests exist: CS, EH, LG, CB, ACJ, EH, SC, RL, MJS, MH, VL, MK, AJR, HC, MK, AR, SL, GDS, SN, KMG, GDK, TRS, RDM, PK., (Copyright: © 2024 Althoff et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: We explored attitudes of gay, bisexual, and other men who have sex with men (GBM) toward their amphetamine-use and associations with reduced use over time., Methods: We recruited sexually-active GBM aged 16+ years in Montreal, Toronto, and Vancouver, Canada, from 02-2017 to 08-2019, with follow-up visits every 6-12 months until November 2020. Among participants who reported past-six-month (P6M) amphetamine-use at enrollment, we used logistic regression to identify demographic, psychological, social, mental health, other substance-use, and behavioral factors associated with reporting needing help reducing their substance-use. We used mixed-effects logistic regression to model reduced P6M amphetamine-use with perceived problematic-use as our primary explanatory variable., Results: We enrolled 2,449 GBM across sites. 15.5-24.7% reported P6M amphetamine-use at enrollment and 82.6 - 85.7% reported needing no help or only a little help in reducing their substance use. Reporting needing a lot/of help or completely needing help in reducing substance-use was associated with group sex participation (AOR = 2.35, 95%CI:1.25-4.44), greater anxiety symptomatology (AOR = 2.11, 95%CI:1.16-3.83), greater financial strain (AOR = 1.35, 95%CI:1.21-1.50), and greater Escape Motive scores (AOR = 1.07, 95%CI:1.03-1.10). Reductions in P6M amphetamine-use were less likely among GBM who perceived their amphetamine-use as problematic (AOR = 0.17 95% CI 0.10 - 0.29)., Conclusions: Most amphetamine-using GBM did not feel they needed help reducing their substance use, and many reported reduced amphetamine-use at subsequent visits. Those who perceived their use as problematic were less likely to reduce their use. Further interventions to assist GBM in reducing their use are needed to assist those who perceive their use as problematic.

Objective: Sexual minority men (SMM) living with HIV report significantly greater methamphetamine use compared with heterosexual and HIV-negative peers. Greater use may be related to stressors (e.g., HIV-related stigma) faced by SMM living with HIV and subsequent psychological and behavioral sequelae. We tested an integrated theoretical model comprised of pathways between stigma, discrimination, childhood sexual abuse, psychological distress, sexual compulsivity, and cognitive escape in predicting methamphetamine use among SMM living with HIV., Methods: Among 423 SMM living with HIV, we tested a structural equation model examining factors hypothesized to be directly and indirectly associated with methamphetamine use. Analyses were adjusted for demographic covariates and sampling bias., Results: The model showed good fit (CFI = 0.96, RMSEA = 0.01). Heterosexist discrimination was associated with psychological distress ( β  = 0.39, p  < 0.001) and psychological distress was associated with sexual compulsivity ( β  = 0.33, p  < 0.001). Sexual compulsivity was associated with cognitive escape ( β  = 0.31, p  < 0.001), which was associated with methamphetamine use ( β  = 0.51, p  < 0.001). Psychological distress was associated with methamphetamine use via serial indirect effects of sexual compulsivity and cognitive escape ( β  = 0.05, p  < 0.05)., Conclusions: Heterosexist discrimination contributed to psychological distress among SMM living with HIV. Psychological distress is linked to methamphetamine use via sexual compulsivity and cognitive avoidance. Interventions seeking to reduce the likelihood that SMM living with HIV use methamphetamine should include coping strategies specific to heterosexism and related psychological distress.

Abstract: Buprenorphine extended-release (BUP-XR) provides sustained delivery of buprenorphine to control withdrawal and craving symptoms in the form of a monthly injectable and has been shown to improve health outcomes in patients with opioid use disorder. It is recommended that patients are stabilized with a transmucosal buprenorphine product, for at least 7 days per the product monograph; however, clinically, this timeline may be expedited. We report a case of a hospitalized patient with unregulated fentanyl use who underwent a successful transdermal buprenorphine induction for 48 hours to initiate BUP-XR with minimal levels of withdrawal and without precipitating opioid withdrawal. The approach described could provide a practical, patient-centered, accelerated induction strategy that, once independently validated, could considerably facilitate the use of BUP-XR., Competing Interests: Pouya Azar is a consultant on Indivior-led buprenorphine extended-release studies, which are unrelated to this case report. The other authors report no conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

Background: Hospital readmission trends for persons with human immunodeficiency virus (PWH) in North America in the context of policy changes, improved antiretroviral therapy (ART), and aging are not well-known. We examined readmissions during 2005-2018 among adult PWH in NA-ACCORD., Methods: Linear risk regression estimated calendar trends in 30-day readmissions, adjusted for demographics, CD4 count, AIDS history, virologic suppression (<400 copies/mL), and cohort., Results: We examined 20 189 hospitalizations among 8823 PWH (73% cisgender men, 38% White, 38% Black). PWH hospitalized in 2018 versus 2005 had higher median age (54 vs 44 years), CD4 count (469 vs 274 cells/μL), and virologic suppression (83% vs 49%). Unadjusted 30-day readmissions decreased from 20.1% (95% confidence interval [CI], 17.9%-22.3%) in 2005 to 16.3% (95% CI, 14.1%-18.5%) in 2018. Absolute annual trends were -0.34% (95% CI, -.48% to -.19%) in unadjusted and -0.19% (95% CI, -.35% to -.02%) in adjusted analyses. By index hospitalization reason, there were significant adjusted decreases only for cardiovascular and psychiatric hospitalizations. Readmission reason was most frequently in the same diagnostic category as the index hospitalization., Conclusions: Readmissions decreased over 2005-2018 but remained higher than the general population's. Significant decreases after adjusting for CD4 count and virologic suppression suggest that factors alongside improved ART contributed to lower readmissions. Efforts are needed to further prevent readmissions in PWH., Competing Interests: Potential conflicts of interest. K. N. A. reports grants to their institution from NIH; royalties or licenses from Coursera; and consulting fees from NIH and TrioHealth. R. J. B. reports grants to their institution from NIH and support for travel from NIH. J. A. C. reports grants to their institution from NIH and payment or honoraria from Prime Education and Integritas Communications. H. M. C. reports grants to their institution from AHRQ, NIH, and ViiV Healthcare; and participation in a data and safety monitoring board (DSMB) or advisory board for Gilead Sciences, NIH Office of AIDS Research, and ViiV Healthcare. J. J. E. reports grants to their institution from NIH, ViiV Healthcare, Gilead Sciences, and Janssen; consulting fees from ViiV Healthcare, Gilead Sciences, and Merck & Co; and participation on a DSMB or advisory board for TAIMED. K. A. G. reports grants to their institution from the US Department of Defense, NIH, Mental Wellness Foundation, HealthNetwork Foundation, Bloomberg Philanthropies, Defense Health Agency, the State of Maryland, Octapharma, Moriah Fund, and National Center for Advancing Translational Sciences; consulting fees from Spark HealthCare, Teach for America, and Aspen Institute; and participation on a DSMB or advisory board for Pfizer. M. J. G. reports grants to their institution from NIH; and participation on a DSMB or advisor board for Merck & Co, Gilead Sciences, and ViiV Healthcare. B. C. H. reports grants to their institution from NIH. M. A. H. reports grants to their institution from NIH. M. Y. K. reports grants to their institution from Gilead Sciences and ViiV Healthcare; payment or honoraria to their institution from Practice Point Communications CME; leadership in the AIDS Clinical Trials Group (ACTG) Underrepresented Populations Committee (Vice Chair) with payments to their institution; and uncompensated leadership on the Being Alive San Diego Board (member). M. B. K. reports grants to their institution from NIH, ViiV Healthcare, AbbVie, and Gilead Sciences; and consulting fees from ViiV Healthcare, AbbVie, and Gilead Sciences. R. L. reports support for travel from CIHR. V. D. L. reports grants to their institution from CIHR; payment or honoraria from ViiV Healthcare; support for travel from the Conference on Retroviruses and Opportunistic Infections; and participation on a DSMB or advisory board for the Providence Health Care Ethics Board. R. D. M. reports grants to their institution from NIH. S. N. reports grants to their institution from NIH. A. N. reports grants to their institution from Gilead Sciences. P. F. R. reports grants to their institution from NIH and consulting fees from Gilead Sciences and Janssen. J. E. T. reports grants to their institution from the National Eye Institute and ACTG; consulting fees from Gilead Sciences, Canfield, and UpToDate; participation on a DSMB or advisory board for NEI and Tarsier; stock or stock options in Tarsier; and fees for serving as Editor-in-Chief for Ocular Immunology and Inflammation. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Characterizing the human immunodeficiency virus (HIV) reservoir that endures despite antiretroviral therapy (ART) is critical to cure efforts. We observed that the oldest proviruses persisting during ART were exclusively defective, while intact proviruses (and rebound HIV) dated to nearer ART initiation. This helps explain why studies that sampled sub-genomic proviruses on-ART (which are largely defective) routinely found sequences dating to early infection, whereas those that sampled replication-competent HIV found almost none. Together with our findings that intact proviruses were more likely to be clonal, and that on-ART low-level/isolated viremia originated from proviruses of varying ages (including possibly defective ones), our observations indicate that (i) on-ART and rebound viremia can have distinct within-host origins, (ii) intact proviruses have shorter lifespans than grossly defective ones and thus depend more heavily on clonal expansion for persistence, and (iii) an HIV reservoir predominantly "dating" to near ART initiation will be substantially adapted to within-host pressures, complicating immune-based cure strategies., Competing Interests: The authors declare no conflict of interest.

Background: Social support has previously been found to be associated with improved health outcomes of individuals managing chronic illnesses, including amongst people living with HIV (PLWH). For women and people who use injection drugs who continue to experience treatment disparities in comparison to other PLWH, social support may have potential in facilitating better treatment engagement and retention. In this analysis, we examined determinants of social support as measured by the Medical Outcomes Study - Social Support Survey (MOS-SSS) scale, and quantified the relationship between MOS-SSS and HIV treatment interruptions (TIs) among PLWH in British Columbia, Canada., Methods: Between January 2016 and September 2018, we used purposive sampling to enroll PLWH, 19 years of age or older living in British Columbia into the STOP HIV/AIDS Program Evaluation study. Participants completed a baseline survey at enrolment which included the MOS-SSS scale, where higher MOS-SSS scores indicated greater social support. Multivariable linear regression modeled the association between key explanatory variables and MOS-SSS scores, whereas multivariable logistic regression modeled the association between MOS-SSS scores and experiencing TIs while controlling for confounders., Results: Among 644 PLWH, we found that having a history of injection drug use more than 12 months ago but not within the last 12 months, self-identifying as Indigenous, and sexual activity in the last 12 months were positively associated with MOS-SSS, while being single, divorced, or dating (vs. married), experiences of lifetime violence, and diagnosis of a mental health disorder were inversely associated. In a separate multivariable model adjusted for gender, ethnicity, recent homelessness, sexual activity in the last 12 months, and recent injection drug use, we found that higher MOS-SSS scores, indicating more social support, were associated with a lower likelihood of HIV treatment interruptions (adjusted odds ratio: 0.90 per 10-unit increase, 95% confidence interval: 0.83, 0.99)., Conclusions: Social support may be an important protective factor in ensuring HIV treatment continuity among PLWH. Future research should examine effective means to build social support among communities that have potential to promote increased treatment engagement., (© 2023. The Author(s).)

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., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)