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Our scoping review sought to describe how Etuaptmumk or Two-Eyed Seeing is used and reported on in Indigenous health research. Using the JBI scoping review methodology, we extracted uses of Etuaptmumk/Two-Eyed Seeing from 83 articles and then categorized the reported uses of Etuaptmumk/Two-Eyed Seeing according to Huria et al.'s eight CONSIDER statement domains (governance, prioritization, relationships, methodologies, participation, capacity, analysis and interpretation, and dissemination). We found that while authors used Etuaptmumk/Two-Eyed Seeing in varied ways and at different stages of their research projects, characterizations of the guiding principle were often insufficiently described or overly simplified. This scoping review intends to contribute to a greater dialogue about how Etuaptmumk/Two-Eyed Seeing is conceptualized and used in Indigenous health research with the goal of encouraging more intentional reporting of the guiding principle., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Roher 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.)

We found that rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing and reverse transcriptase (RT)-PCR-confirmed infection were approximately 50% higher in a population-based cohort of people with HIV compared with a matched cohort of people without HIV during the Omicron era (2 January 2022 to 31 March 2023) in Ontario, Canada, after controlling for age, sex, residential census tract, and country of birth. Rates of coronavirus disease 2019 (COVID-19)-related hospitalization and/or death were more than double. Differences persisted independent of vaccination, healthcare access, and COVID-19 diagnosis., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The ongoing opioid overdose crisis, which has killed over 30,000 people in Canada since 2016, is driven by the volatility of an unregulated opioid drug supply comprised primarily of fentanyl. The Canadian government has recently funded safer opioid supply (SOS) programs, which include off-label prescriptions of pharmaceutical-grade opioids to high risk individuals with the goal of reducing overdose deaths., Methods: In 2021, we examined the implementation and adaption of four SOS programs in Ontario. These programs use a primary care model and serve communities experiencing marginalisation. We conducted semi-structured interviews with program clients. We present the results of a thematic analysis with the aim of describing clients' self-reported impact of these programs on their health and well-being., Results: We interviewed 52 clients between June and October 2021 (mean age 47 years, 56% men, 17% self-identified Indigenous, 14% living with HIV). Our results indicate multifaceted pathways to improved self-reported health and well-being among clients including changes to drug use practices, fewer overdoses, reduced criminalised activity, improved trust and engagement in health care, and increased social stability (e.g., housing)., Discussion and Conclusion: Most clients reported that the intervention saved their life because of the reduced frequency of overdoses. Findings suggest that SOS programs improved clients' health outcomes and increase opportunities for engagement in health services. Our results provide insight into the mechanisms behind some of the emergent evidence on the impact of safer supply prescribing., (© 2023 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

We examined the effectiveness of a 26-week culture-inclusive intervention on reducing salivary stress biomarker levels, and perceived stress, depressive, and post-traumatic stress disorder (PTSD) symptoms measured using scales in 53 Indigenous women in Ontario, Canada. Statistical analyses compared the average biomarker levels, and the area under the curve (AUC) of biomarkers. Differences in biomarkers and mental health scale scores pre- and post-intervention were compared using mixed models with a random intercept. Interaction terms were included between the intervention and age, education, disability, and HIV status, individually, to test for sub-group differences. Cortisol AUC post-intervention was decreased compared to pre-intervention (β -1.29 µg/dL; 95%CI -2.35, -0.23). There was a slight decrease in perceived stress levels (aOR: -2.80; 95%CI -5.09, -0.50). The associations were stronger among women of younger age, higher education, and no disabilities. These interventions can be effective, but future interventions should target Indigenous population sub-groups to address individual needs., (© 2023. The Author(s).)

Access to cultural activities and culturally relevant healthcare has always been significant for achieving holistic Indigenous health and continues to be a key factor in shaping the health journey of Indigenous individuals and communities. Previous research has indicated the importance of cultural practices and services in sustaining cultural identity for Indigenous peoples, which is a major influence on their wellbeing. This study marks the first phase in a project aimed at establishing an Indigenous healing program and uses a qualitative research approach to understand the health and cultural services that Indigenous women want and require in Thunder Bay, Ontario. During interviews, participants (n = 22) answered questions around their understandings of health and wellbeing, and how they are able to incorporate cultural practices into their circle of care. Thematic analysis was performed on interview transcripts, and 4 key themes were identified: 'independence and self-care', 'external barriers to accessing services', 'finding comfort in the familiar' and 'sense of community'. Together these themes illustrate how Indigenous women feel a strong sense of personal responsibility for maintaining their health despite the multiple environmental factors that may act as barriers or supports. Furthermore, the necessity of embedding cultural practices into Indigenous women's circle of care is highlighted by the participants as they describe the mental, spiritual, social, and emotional health benefits of engaging in cultural activities within their community. The findings demonstrate the need for current modes of care to look beyond the individual and consider the impacts that socio-environmental factors have on Indigenous women. To accomplish this, we hope to increase access to health and cultural services through the creation of an Indigenous healing program that can be adequately incorporated into Indigenous women's circle of care if they wish to do so., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lin 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.)

Objective: People with HIV were underrepresented in coronavirus disease 2019 (COVID-19) vaccine clinical trials. We estimated vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for the BNT162b2, mRNA-1273, and ChAdOx1 vaccines among a population-based cohort of people with HIV in Ontario, Canada., Design: Test-negative design., Methods: We identified people with HIV aged ≥19 years who were tested for SARS-CoV-2 by RT-PCR between December 14, 2020 (first availability of COVID-19 vaccines) and November 21, 2021 (pre-Omicron circulation). Outcomes included any infection, symptomatic infection, and COVID-19-related hospitalization/death. We compared the odds of vaccination between test-positive cases and test-negative controls using multivariable logistic regression with adjustment for age, sex, region, calendar time, SARS-CoV-2 test histories, influenza vaccination, comorbidities, and neighborhood-level socio-economic status. VE was derived as (1 - adjusted odds ratio) × 100%., Results: Among 21 023 adults living with HIV, there were 801 (8.3%) test-positive cases and 8,879 (91.7%) test-negative controls. 20.1% cases and 47.8% of controls received ≥1 COVID-19 vaccine dose; among two-dose recipients, 93.4% received ≥1 mRNA dose. Two-dose VE ≥7 days before specimen collection was 82% (95% confidence interval [CI] = 74-87%) against any infection, 94% (95% CI = 82-98%) against symptomatic infection, and 97% (95% CI = 85-100%) against hospitalization/death. Against any infection, VE declined from 86% (95% CI = 77-92%) within 7-59 days after the second dose to 66% (95% CI = -15-90%) after ≥180 days; we did not observe evidence of waning protection for other outcomes., Conclusion: Two doses of COVID-19 vaccine offered substantial protection against symptomatic illness and hospitalization/death in people with HIV prior to the emergence of the Omicron variant. Our findings do not support a broad conclusion that COVID-19 VE is lower among people with HIV in populations that, for the most part, are attending HIV care, taking antiretroviral medication, and are virally suppressed., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Women living with HIV are at higher risk for human papillomavirus (HPV)-related dysplasia and cancers and thus are prioritized for HPV vaccination. We measured HPV vaccine uptake among women engaged in HIV care in Ontario, Canada, and identified socio-demographic, behavioural, and clinical characteristics associated with HPV vaccination. During annual interviews from 2017 to 2020, women participating in a multi-site, clinical HIV cohort responded to a cross-sectional survey on HPV vaccine knowledge and receipt. We used logistic regression to derive age-adjusted odds ratios and 95% confidence intervals (CI) for factors associated with self-reported vaccine initiation (≥1 dose) or series completion (3 doses). Among 591 women (median age = 48 years; interquartile range = 40-56 years), 13.2% (95%CI = 10.5-15.9%) had received ≥1 dose. Of those vaccinated, 64.6% had received 3 doses. Vaccine initiation (≥1 dose) was significantly higher among women aged 20-29 years at 31.0% but fell to 13.9% in those aged 30-49 years and < 10% in those aged ≥50 years. After age adjustment, vaccine initiation was significantly associated with being employed (vs. unemployed but seeking work), income $40,000-$59,999 (vs. <$20,000), being married/common-law (vs. single), living with children, immigrating to Canada >5 years ago (vs. immigrating ≤5 years ago), never smoking (vs. currently smoking), and being in HIV care longer (per 10 years). Similar factors were identified for series completion (3 doses). HPV vaccine uptake remains low among women living with HIV in our cohort despite regular engagement in care. Recommendations for improving uptake include education of healthcare providers, targeted community outreach, and public funding of HPV vaccination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the effects of psychological, psychosocial, educational and alternative interventions on mental health outcomes of Indigenous adult populations in Australia, Canada, New Zealand and the United States and the Indigenous involvement and content in each study., Methods: We systematically searched databases, key journals and gray literature, for records until June 2020. Eligible studies were in English or French and examined the impact of interventions on mental health outcomes including anxiety disorders, posttraumatic stress disorder, depression, psychological distress or stress for Indigenous adults (⩾16 years). Data were extracted using a modified Cochrane Data Extraction Form and the Template for Intervention Description and Replication. Quality was evaluated using the Effective Public Health Practice Project quality assessment form., Results: In total, 21 studies were eligible, comprising 8 randomized controlled trials, 10 single-group pre-post studies and 3 pre-post studies with comparison groups. Twenty studies had Indigenous individuals or organizations involved in some decision-making capacity, though extent of involvement varied widely. In total, 9 studies were rated moderate and 12 weak in the Effective Public Health Practice Project quality assessment. Eight studies measuring depression, three measuring posttraumatic stress disorder, three measuring psychological distress and two measuring stress showed statistically significant improvements following the intervention., Conclusion: A wide range of interventions demonstrated mental health improvements. However, it is difficult to draw generalizable conclusions on intervention effectiveness, given heterogeneity among studies. Studies should employ a thorough assessment of the Indigenous involvement and content of their interventions for reporting and for critical consideration of the implications of their research and whether they address Indigenous determinants of mental health.

Background: Hydraulic fracturing (fracking) is a method used to extract unconventional natural gas (UNG). Living near UNG operations has been associated with various health outcomes, but few have explored the association between UNG and mental health and substance use. Our objective was to evaluate the association between metrics of residential UNG well density/proximity and mental illness and substance use among pregnant individuals in Northeastern British Columbia, Canada., Methods: Individuals who gave birth at the Fort St John hospital between December 30, 2006 and December 29, 2016 (n = 6278) were included in the study. Exposure was determined using inverse distance weighting (IDW) to calculate the density and proximity of UNG wells to the postal code centroid ofindividual's residential address at delivery. Four exposure metrics, categorized by quartiles, were calculated based on 50, 10, 5 and 2.5 km buffer zones around each postal code centroid. Logistic regression was used to separately evaluate associations between IDW quartiles of each metric and diagnosis of depression and anxiety prior to or during pregnancy, and self-reported substance use during pregnancy, controlling for relevant and available confounders., Results: The second and third quartile (Q) of the 10 km IDW were associated with greater odds of depression (Q2: adjusted (aOR) 1.30, 95% (confidence interval) CI 1.03-1.64; Q3: aOR 1.35, 95% CI 1.07-1.70) compared to the first quartile, but not the fourth. Using the 5 km IDW, we observed a suggestive positive association with depression in the second and third quartile (aOR Q2: 1.21, 95% CI 0.96-1.53; aOR Q3: 1.24, 95% CI 0.98-1.57) compared to the first quartile. No statistically significant association was observed using the 2.5 km IDW exposure metric., Conclusion: We observed some evidence of greater odds of mental illness prior to or during pregnancy, and substance use during pregnancy in pregnant individuals living in postal codes with increased UNG well density/proximity, although associations were not observed in smaller buffer zones. This study adds to the growing literature on the adverse health outcomes surrounding living in proximity to UNG operations., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Our scoping review sought to consider how Etuaptmumk or Two-Eyed Seeing is described in Indigenous health research and to compare descriptions of Two-Eyed Seeing between original authors (Elders Albert and Murdena Marshall, and Dr. Cheryl Bartlett) and new authors. Using the JBI scoping review methodology and qualitative thematic coding, we identified seven categories describing the meaning of Two-Eyed Seeing from 80 articles: guide for life, responsibility for the greater good and future generations, co-learning journey, multiple or diverse perspectives, spirit, decolonization and self-determination, and humans being part of ecosystems. We discuss inconsistencies between the original and new authors, important observations across the thematic categories, and our reflections from the review process. We intend to contribute to a wider dialogue about how Two-Eyed Seeing is understood in Indigenous health research and to encourage thoughtful and rich descriptions of the guiding principle., Competing Interests: The authors have declared no competing interests exist.

The use of data intensive health research has allowed for greater understandings of population health. When conducting data intensive health research, engaging and involving the community is essential for conducting meaningful research that is responsive to the public's needs. Particularly, when engaging Indigenous communities in research, there is a need to understand historical and ongoing impacts of colonialism and recognize the strengths in Indigenous Peoples' knowledges and experiences while supporting Indigenous leadership and self-determination in research. This article describes the approach our research team/organization used to engage and involve Indigenous people living with HIV in three research projects using large, linked datasets and looking at HIV outcomes of Indigenous populations in Canada. The foundation of these projects was simultaneously: 1) supporting Indigenous people living with HIV to be involved as research team members, 2) developing research questions to answer with available datasets, and 3) integrating Indigenous and Western ways of knowing. We have identified important considerations and suggestions for engaging and involving Indigenous communities and individuals in the generation of research ideas and analysis of linked data using community-based participatory research approaches through our work. These include engaging stakeholders at the start of the project and involving them throughout the research process, honouring Indigenous ways of knowing, the land, and local protocols and traditions, prioritizing Indigenous voices, promoting co-learning and building capacity, and focusing on developing longitudinal relationships. We describe keys to success and learnings that emerged. Importantly, the methodology practiced and presented in this manuscript is not  a qualitative study design whereby research subjects are surveyed about their experiences or beliefs. Rather, the study approach described herein is about engaging people with living experience to co-lead as researchers. Our approach supported Indigenous people to share research that addresses their research priorities and responds to issues relevant to Indigenous Peoples and communities., Competing Interests: Statement on conflicts of interest: No conflicts of interest

Objectives: We sought to map the evidence and identify interventions that increase initiation of antiretroviral therapy, adherence to antiretroviral therapy and retention in care for people living with HIV at high risk for poor engagement in care., Methods: We conducted an overview of systematic reviews and sought for evidence on vulnerable populations (men who have sex with men (MSM), African, Caribbean and Black (ACB) people, sex workers (SWs), people who inject drugs (PWID) and indigenous people). We searched PubMed, Excerpta Medica dataBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Web of Science and the Cochrane Library in November 2018. We screened, extracted data and assessed methodological quality in duplicate and present a narrative synthesis., Results: We identified 2420 records of which only 98 systematic reviews were eligible. Overall, 65/98 (66.3%) were at low risk of bias. Systematic reviews focused on ACB (66/98; 67.3%), MSM (32/98; 32.7%), PWID (6/98; 6.1%), SWs and prisoners (both 4/98; 4.1%). Interventions were: mixed (37/98; 37.8%), digital (22/98; 22.4%), behavioural or educational (9/98; 9.2%), peer or community based (8/98; 8.2%), health system (7/98; 7.1%), medication modification (6/98; 6.1%), economic (4/98; 4.1%), pharmacy based (3/98; 3.1%) or task-shifting (2/98; 2.0%). Most of the reviews concluded that the interventions effective (69/98; 70.4%), 17.3% (17/98) were neutral or were indeterminate 12.2% (12/98). Knowledge gaps were the types of participants included in primary studies (vulnerable populations not included), poor research quality of primary studies and poorly tailored interventions (not designed for vulnerable populations). Digital, mixed and peer/community-based interventions were reported to be effective across the continuum of care., Conclusions: Interventions along the care cascade are mostly focused on adherence and do not sufficiently address all vulnerable populations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We aimed to identify the association between stress and antiretroviral therapy (ART) adherence among women in HIV care in Toronto, Ontario participating in the Ontario HIV Treatment Network Cohort Study (OCS) between 2007 and 2012., Materials and Methods: We conducted cross-sectional analyses with women on ART completing the AIDS Clinical Trial Group (ACTG) Adherence Questionnaire. Data closest to, or at the last completed interview, were collected from medical charts, through record linkage with Public Health Ontario Laboratories, and from a standardized self-reported questionnaire comprised of socio-demographic and psycho-socio-behavioral measures (Center for Epidemiologic Studies Depression Scale (CES-D), Alcohol Use Disorders Identification Test (AUDIT)), and stress measures (National Population Health Survey). Logistic regression was used to quantify associations with optimal adherence (≥95% adherence defined as missing ≤ one dose of ART in the past 4 weeks)., Results: Among 307 women, 65.5% had optimal adherence. Women with suboptimal compared to optimal adherence had higher median total stress scores (6.0 [interquartile range (IQR): 3.0-8.1] vs. 4.1 [IQR: 2.0-7.1], p = 0.001), CES-D scores (16 [IQR: 6-28] vs. 12 [IQR: 3-22], p = 0.008) and reports of hazardous and harmful alcohol use (31.1% vs. 17.9%, p = 0.008). In our multivariable model, we found an increased likelihood of optimal adherence with the absence of hazardous and harmful alcohol use (Adjusted Odds Ratio (AOR)=2.20, 95% confidence interval (CI): 1.12-4.32) and a decreased likelihood of optimal adherence with more self-reported stress (AOR = 0.56, 95% CI: 0.33-0.94)., Conclusions: Interventions supporting optimal ART adherence should address stress and include strategies to reduce or eliminate hazardous and harmful alcohol use for women living with HIV.

Background: Processes for epidemiology embedded with Indigenous methodology are needed. Building Bridges was developed to engage Indigenous peoples in epidemiology to address health issues relevant to them., Objectives: We describe our process for meaningfully engaging Indigenous leaders and peoples living with human immunodeficiency virus (HIV) in epidemiology research., Methods: As a community-based research (CBR) project, Indigenous methodologies and leadership ensured the quality and relevance of findings. Study phases included 1) advisory board formation, 2) recruitment, 3) research question identification, 4) data analysis from the Canadian HIV Observational Cohort (CANOC) collaboration, 5) data interpretation and contextualization, and 6) knowledge translation and exchange., Lessons Learned: Support and guidance from Indigenous team members, Spiritual Leaders and Elders along with meaningful relationships with allied academic researchers were pivotal. Expertise and lived experiences in Indigenous culture, HIV, epidemiology and services enabled multidirectional learning., Conclusions: Building Bridges' success hinged on ongoing co-learning and engagement of Indigenous peoples, service providers and researchers.

Background: A community-based research (CBR) approach is critical to redressing the exclusion of women-particularly, traditionally marginalized women including those who use substances-from HIV research participation and benefit. However, few studies have articulated their process of involving and engaging peers, particularly within large-scale cohort studies of women living with HIV where gender, cultural and linguistic diversity, HIV stigma, substance use experience, and power inequities must be navigated., Methods: Through our work on the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS), Canada's largest community-collaborative longitudinal cohort of women living with HIV (n = 1422), we developed a comprehensive, regionally tailored approach for hiring, training, and supporting women living with HIV as Peer Research Associates (PRAs). To reflect the diversity of women with HIV in Canada, we initially hired 37 PRAs from British Columbia, Ontario, and Quebec, prioritizing women historically under-represented in research, including women who use or have used illicit drugs, and women living with HIV of other social identities including Indigenous, racialized, LGBTQ2S, and sex work communities, noting important points of intersection between these groups., Results: Building on PRAs' lived experience, research capacity was supported through a comprehensive, multi-phase, and evidence-based experiential training curriculum, with mentorship and support opportunities provided at various stages of the study. Challenges included the following: being responsive to PRAs' diversity; ensuring PRAs' health, well-being, safety, and confidentiality; supporting PRAs to navigate shifting roles in their community; and ensuring sufficient time and resources for the translation of materials between English and French. Opportunities included the following: mutual capacity building of PRAs and researchers; community-informed approaches to study the processes and challenges; enhanced recruitment of harder-to-reach populations; and stronger community partnerships facilitating advocacy and action on findings., Conclusions: Community-collaborative studies are key to increasing the relevance and impact potential of research. For women living with HIV to participate in and benefit from HIV research, studies must foster inclusive, flexible, safe, and reciprocal approaches to PRA engagement, employment, and training tailored to regional contexts and women's lives. Recommendations for best practice are offered.

Introduction: While access to antiretroviral therapy (ART) for people living with HIV has expanded in recent years, additional efforts are required to support adherence to medication and retention in care. Interventions should be applicable in real-world settings and amenable to widespread use. The objectives of this overview are to identify effective pragmatic interventions that increase adherence to ART and retention in care for people living with HIV at high risk for suboptimal adherence and retention in high-income countries., Methods and Analysis: We will conduct an overview of systematic reviews of studies on interventions which target improved adherence to medication and retention in care among high-risk people living with HIV in high-income countries (men who have sex with men, African, Caribbean and black people, sex workers, people who inject drugs, indigenous people and other socially marginalised groups). We will search the following databases: PubMed, EMBASE (Exerpta Medica Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of Science and the Cochrane Library. We will conduct screening, data extraction and assessment of methodological quality of the systematic reviews. Analysis will be narrative. Our findings will be interpreted in light of the certainty of the evidence, level of pragmatism, setting and population of interest., Ethics and Dissemination: Only published secondary data will be used in this study, and therefore ethics approval is not required. Our findings will be disseminated as peer-reviewed manuscripts, conference abstracts and through community activities. The findings from this overview will inform a mixed-methods study among people living with HIV and health workers in Ontario, Canada., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Teenage mothers are at increased risk for adverse social outcomes and short-term health problems, but long-term impacts on mental health are poorly understood. The aims of our systematic review were to determine the association between teenage pregnancy and mental health beyond the postpartum period, critically appraise the literature's quality and guide future research., Methods: We systematically searched MEDLINE, Embase, PsycINFO, CINAHL, Scopus and Web of Science from inception to June 2017 for peer-reviewed articles written in English or French. Data were collected using a modified Cochrane Data Extraction Form. Study quality was assessed using the Effective Public Health Practice Project critical appraisal tool. Heterogeneity of studies permitted only a qualitative synthesis., Results: Nine quantitative studies comprising the results from analyses of 11 cohorts met our criteria and were rated as strong (n=5), moderate (n=2) or weak (n=2). Three cohorts found a statistically significant association between teenage pregnancy and poor long-term mental health after adjustment, three found a statistically significant association before but not after adjustment and five did not find a statistically significant association. Studies observed varying degrees of attenuation after considering social context. Studies with statistically significant findings tended to comprise earlier cohorts, with outcomes measured at older ages., Conclusions: The association between teenage pregnancy and mental health beyond the postpartum period remains unclear. Future studies should employ age-period-cohort frameworks to disentangle effects of normative patterns and stress accumulation. Social factors are important in determining long-term mental health of teenage mothers and should be prioritised in prevention and intervention strategies., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Our objectives were to (1) compare the risks for poor long-term mental health outcomes among indigenous women with and without a teenage pregnancy and (2) determine if community and cultural factors modify this risk. We conducted a secondary analysis of the 2012 Aboriginal Peoples Survey. Respondents were women aged 25 to 49 years who had given birth to at least one child. Teenage mothers (age at first birth 13 to 19 years; n = 1330) were compared to adult mothers (age at first birth 20 years or older; n = 2630). Mental health outcomes were psychological distress, mental health status, suicide ideation/attempt, and alcohol consumption. To address objective 1, we used binary logistic regression analyses before and after controlling for covariates. To address objective 2, we tested the significance of interaction terms between teenage pregnancy status and effect measure modifiers. In unadjusted analyses, teenage pregnancy was associated with increased risk for poor/fair mental health [odds ratio (OR) 1.77, 95% confidence interval (CI) 1.24-2.53] and suicide attempt/ideation (OR 1.95, 95% CI 1.07-3.54). However, the associations were not statistically significant after adjusting for demographic, socioeconomic, environmental, and health covariates. Teenage pregnancy was not associated with increased risk for high psychological distress or heavy alcohol consumption in unadjusted or adjusted analyses. The interaction term for involvement in cultural activities was statistically significant for poor/fair mental health; however, after stratification, ORs were non-significant. Among indigenous mothers, teenage pregnancy was less important than broader social and health circumstances in predicting long-term mental health.

We sought to estimate the prevalence of childhood adversity and examine its relationship with health outcomes among people living with HIV. Study participants included 1409 adults living with HIV and receiving care in Toronto, Canada. Data on childhood adversity, health behaviors, HIV outcome measures, depression, and health-related quality of life (HRQOL) were collected through face-to-face interviews and medical records. Statistical analyses included multivariable linear and logistic regression modeling. The prevalence of any childhood adversity was 71% (individual types ranged from 11% to 44%) and higher prevalence was associated with younger age, Indigenous or African/Caribbean/Black ethnicity, lower socioeconomic status, and higher rates of cigarette smoking and nonmedicinal drug use. Greater number of childhood adversities was associated with greater odds of depression and decreasing mental HRQOL. HIV care providers need to screen for childhood adversities and address childhood trauma within the context of HIV care.

Background: Associations between HIV-related stigma and reduced antiretroviral therapy (ART) adherence are widely established, yet the mechanisms accounting for this relationship are underexplored. There has been less attention to HIV-related stigma and its associations with ART initiation and current ART use. We examined pathways from HIV-related stigma to ART initiation, current ART use, and ART adherence among women living with HIV in Canada., Methods: We used baseline survey data from a national cohort of women living with HIV in Canada (n = 1425). Structural equation modeling using weighted least squares estimation methods was conducted to test the direct effects of HIV-related stigma dimensions (personalized, negative self-image, and public attitudes) on ART initiation, current ART use, and 90% ART adherence, and indirect effects through depression and HIV disclosure concerns, adjusting for sociodemographic factors., Results: In the final model, the direct paths from personalized stigma to ART initiation (β = -0.104, P < 0.05) and current ART use (β = -0.142, P < 0.01), and negative self-image to ART initiation (β = -0.113, P < 0.01) were significant, accounting for the mediation effects of depression and HIV disclosure concerns. Depression mediated the pathways from personalized stigma to ART adherence, and negative self-image to current ART use and ART adherence. Final model fit indices suggest that the model fit the data well [χ(25) = 90.251, P < 0.001; comparative fit index = 0.945; root-mean-square error of approximation = 0.044]., Conclusions: HIV-related stigma is associated with reduced likelihood of ART initiation and current ART use, and suboptimal ART adherence. To optimize the benefit of ART among women living with HIV, interventions should reduce HIV-related stigma and address depression.

In Canada, Indigenous women are more likely than non-Indigenous women to be survivors of sexual assault and experience sexual assaults that are more serious in terms of physical injury and other health-related consequences. Despite their related needs for care and support, there is a paucity of research to date that has examined their uptake of specialized acute health services post sexual assault. To address this gap, we explored the presentation, sociodemographic, assailant, assault, and service use characteristics of Indigenous women, as compared to non-Indigenous adult and adolescent women aged 12 and older presenting to 30 of 35 hospital-based sexual assault treatment centres in Ontario from 2009 to 2011, using bivariate analyses. Of the 948 women in our sample, 116 (12%) identified as being Indigenous. Indigenous survivors differed significantly from non-Indigenous survivors on many presentation, sociodemographic, and assault characteristics. For example, they were more likely to present to a hospital within 24 hours of being assaulted and a treatment centre serving a primarily rural population. They tended to be younger, were more likely to be living in an institutional setting, report community or group affiliations and government or community services as sources of social support, and be assaulted by a parent, guardian, or other relative. In terms of receipt of services, they were more likely to have undergone safety planning and to be referred to child protection or community agencies. They reported high levels of satisfaction with the services received, however, were less likely than non-Indigenous survivors to rate the overall care provided as excellent or good. On the whole, the results of our study suggest that Indigenous women value acute hospital-based sexual assault services. However, they experience sexual assaults in contexts different from non-Indigenous survivors. It is important for health care providers to be attuned to this so that they can appropriately respond to their unique needs.

Background: The "cascade of care" is a framework for quantifying the trajectory of people with HIV along the continuum of HIV care. We extended this framework to recognize that individuals may transition back and forth between states of care and to identify factors associated with movement among states of care over time, with particular focus on stress, depression, and adherence., Methods: The Ontario HIV Treatment Network Cohort Study is a multisite HIV clinical cohort. We analyzed data from participants who had initiated antiretroviral therapy, achieved virologic suppression, completed ≥1 study questionnaire including psychosocial data, and had ≥1 viral load (VL) result within 2 years of a questionnaire. Follow-up time from the first suppressed VL was divided into 6-month intervals and classified into 1 of 3 states for HIV care retention: (1) suppressed VL (VL <50 copies/mL), (2) unsuppressed VL (VL >50 copies/mL), and (3) unobserved. Multistate models were used to determine the association of transitioning between states and time-updated demographic and clinical characteristics., Results: In total, 1842 participants were included. After multivariable adjustment, poor adherence [hazard ratio (HR) 1.88, 95% confidence interval (CI): 1.19 to 2.98) and stress (HR = 1.38; 95% CI: 1.04 to 1.83) were associated with transitions from suppressed to unsuppressed VL. Similarly, low adherence (HR = 1.52; 95% CI: 1.14 to 2.04) and stress (HR = 1.25; 95%: 1.03, 1.51) were associated with transitions from suppressed to unobserved states., Conclusions: Higher levels of stress and low adherence are associated with transitions to less favorable states of care. Interventions to manage stress and facilitate adherence may improve engagement in HIV care.

Globally, women are at increased vulnerability to HIV due to biological, social, structural, and political reasons. Women living with HIV also experience unique issues related to their medical and social healthcare, which makes a clinical care model specific to their needs worthy of exploration. Furthermore, there is a dearth of research specific to women living with HIV. Research for this population has often been narrowly focused on pregnancy-related issues without considering their complex structural inequalities, social roles, and healthcare and biological needs. For these reasons, we have come together, as researchers, clinicians and community members in Canada, to develop the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) to investigate the concept of women-centred HIV care (WCHC) and its impact on the overall, HIV, women's, mental, sexual, and reproductive health outcomes of women living with HIV. Here, we present the CHIWOS cohort profile, which describes the cohort and presents preliminary findings related to perceived WCHC. CHIWOS is a prospective, observational cohort study of women living with HIV in British Columbia (BC), Ontario, and Quebec. Two additional Canadian provinces, Saskatchewan and Manitoba, will join the cohort in 2018. Using community-based research principles, CHIWOS engages women living with HIV throughout the entire research process meeting the requirements of the 'Greater Involvement of People living with HIV/AIDS'. Study data are collected through an interviewer-administered questionnaire that uses a web-based platform. From August 2013 to May 2015, a total of 1422 women living with HIV in BC, Ontario, and Quebec were enrolled and completed the baseline visit. Follow-up interviews are being conducted at 18-month intervals. Of the 1422 participants at baseline, 356 were from BC (25%), 713 from Ontario (50%), 353 from Quebec (25%). The median age of the participants at baseline was 43 years (range, 16-74). 22% identified as Indigenous, 30% as African, Caribbean or Black, 41% as Caucasian/White, and 7% as other ethnicities. Overall, 83% of women were taking antiretroviral therapy at the time of the baseline interview and of them, 87% reported an undetectable viral load. Of the 1326 women who received HIV medical care in the previous year and responded to corresponding questions, 57% (95% CI: 54%-60%) perceived that the care they received from their primary HIV doctor had been women-centred. There were provincial and age differences among women who indicated that they received WCHC versus not; women from BC or Ontario were more likely to report WCHC compared to participants in Quebec. They were also more likely to be younger. CHIWOS will be an important tool to develop care models specific for women living with HIV. Moreover, CHIWOS is collecting extensive information on socio-demographics, social determinants of health, psychological factors, and sexual and reproductive health and offers an important platform to answer many relevant research questions for and with women living with HIV. Information on the cohort can be found on the study website (http://www.chiwos.ca).

Continuous HIV care supports antiretroviral therapy initiation and adherence, and prolongs survival. We investigated the association of social determinants of health (SDH) and subsequent retention in HIV care in a clinical cohort in Ontario, Canada. The Ontario HIV Treatment Network Cohort Study is a multi-site cohort of patients at 10 HIV clinics. Data were collected from medical charts, interviews, and via record linkage with the provincial public health laboratory for viral load tests. For participants interviewed in 2009, we used three-category multinomial logistic regression to identify predictors of retention in 2010-2012, defined as (1) continuous care (≥2 viral loads ≥90 days in all years; reference category); (2) discontinuous care (only 1 viral load/year in ≥1 year); and (3) a gap in care (≥1 year in 2010-2012 with no viral load). In total, 1838 participants were included. In 2010-2012, 71.7% had continuous care, 20.9% had discontinuous care, and 7.5% had a gap in care. Discontinuous care in 2009 was predictive (p < .0001) of future retention. SDH associated with discontinuous care were Indigenous ethnicity, being born in Canada, being employed, reporting hazardous drinking, and non-injection drug use. Being a heterosexual male was associated with having a gap in care, and being single and younger were associated with discontinuous care and a gap in care. Various SDH were associated with retention. Care discontinuity was highly predictive of future gaps. Targeted strategic interventions that better engage those at risk of suboptimal retention merit exploration., Abbreviations: AOR: adjusted odds ratio; ART: antiretroviral therapy; AUDIT: Alcohol Use Disorders Identification Test; CES-D: Center for Epidemiologic Studies Depression Scale; CIs: confidence intervals; HIV: human immunodeficiency virus; IQR: interquartile range; MSM: men who have sex with men; NA-ACCORD: North American AIDS Cohort Collaboration on Research and Design; OCS: Ontario HIV Treatment Network Cohort Study; OHTN: Ontario HIV Treatment Network; OR: odds ratio; PHOL: Public Health Ontario Laboratories; REB: Research Ethics Board; SDH: social determinants of health; US: United States.

Objective: Compare all-cause mortality between Indigenous participants and participants of other ethnicities living with HIV initiating combination antiretroviral therapy (cART) in an interprovincial multi-site cohort., Methods: The Canadian Observational Cohort is a collaboration of 8 cohorts of treatment-naïve persons with HIV initiating cART after January 1, 2000. Participants were followed from the cART initiation date until death or last viral load (VL) test date on or before December 31, 2012. Cox proportional hazard models were used to estimate the effect of ethnicity on time until death after adjusting for age, gender, injection drug use, being a man who has sex with men, hepatitis C, province of origin, baseline VL and CD4 count, year of cART initiation and class of antiretroviral medication., Results: The study sample consisted of 7080 participants (497 Indigenous, 2471 Caucasian, 787 African/Caribbean/Black (ACB), 629 other, and 2696 unknown ethnicity). Most Indigenous persons were from British Columbia (BC) (83%), with smaller numbers from Ontario (13%) and Québec (4%). During the study period, 714 (10%) participants died. The five-year survival probability was lower for Indigenous persons (0.77) than for Caucasian (0.94), ACB (0.98), other ethnicities (0.96) and unknown ethnicities (0.85) (p &lt; 0.0001). In an adjusted proportional hazard model for which missing data were imputed, Indigenous persons were more likely to die than Caucasian participants (hazard ratio = 2.69, p &lt; 0.0001)., Conclusion: The mortality rate for Indigenous persons was higher than for other ethnicities and is largely reflective of the BC population. Addressing treatment challenges and identifying HIV- and non-HIV-related causes for mortality among Indigenous persons is required to optimize their clinical management.

Background: This study compared time to virological suppression and rebound between Indigenous and non-Indigenous individuals living with HIV in Canada initiating combination antiretroviral therapy (cART)., Methods: Data were from the Canadian Observational Cohort collaboration; eight studies of treatment-naive persons with HIV initiating cART after 1/1/2000. Fine and Gray models were used to estimate the effect of ethnicity on time to virological suppression (two consecutive viral loads [VLs] <50 copies/ml at least 3 months apart) after adjusting for the competing risk of death and time until virological rebound (two consecutive VLs >200 copies/ml at least 3 months apart) following suppression., Results: Among 7,080 participants were 497 Indigenous persons of whom 413 (83%) were from British Columbia. The cumulative incidence of suppression 1 year after cART initiation was 54% for Indigenous persons, 77% for Caucasian and 80% for African, Caribbean or Black (ACB) persons. The cumulative incidence of rebound 1 year after suppression was 13% for Indigenous persons, 6% for Caucasian and 7% for ACB persons. Indigenous persons were less likely to achieve suppression than Caucasian participants (aHR=0.58, 95% CI 0.50, 0.68), but not more likely to experience rebound (aHR=1.03, 95% CI 0.84, 1.27) after adjusting for age, gender, injection drug use, men having sex with men status, province of residence, baseline VL and CD4 + T-cell count, antiretroviral class and year of cART initiation., Conclusions: Lower suppression rates among Indigenous persons suggest a need for targeted interventions to improve HIV health outcomes during the first year of treatment when suppression is usually achieved.

We measured stress, depression and post-traumatic stress disorder (PTSD) levels of urban Indigenous women living with and without HIV in Ontario, Canada, and identified correlates of depression. We recruited 30 Indigenous women living with HIV and 60 without HIV aged 18 years or older who completed socio-demographic and health questionnaires and validated scales assessing stress, depression and PTSD. Descriptive statistics were conducted to summarize variables and linear regression to identify correlates of depression. 85.6 % of Indigenous women self-identified as First Nation. Co-morbidities other than HIV were self-reported by 82.2 % (n = 74) of the sample. High levels of perceived stress were reported by 57.8 % (n = 52) of the sample and 84.2 % (n = 75) had moderate to high levels of urban stress. High median levels of race-related (51/88, IQR 42-68.5) and parental-related stress (40.5/90, IQR 35-49) scores were reported. 82.2 % (n = 74) reported severe depressive symptoms and 83.2 % (n = 74) severe PTSD. High levels of perceived stress was correlated with high depressive symptoms (estimate 1.28 (95 % CI 0.97-1.58), p < 0.001). Indigenous women living with and without HIV reported elevated levels of stress and physical and mental health concerns. Interventions cutting across diverse health care settings are required for improving and preventing adverse health outcomes.

Background: The resistance profiles for patients on first-line antiretroviral therapy (ART) regimens after viremia have not been well studied in community clinic settings in the modern treatment era., Objective: To determine time to viremia and the ART resistance profiles of viremic patients., Methods: HIV-positive patients aged ≥16 years initiating a three-drug regimen were retrospectively identified from 01/01/06 to 12/31/12. The regimens were a backbone of two nucleoside reverse transcriptase inhibitors (NRTIs) and a third agent: a protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or an integrase inhibitor (II). Time to viremia was compared using a proportional hazards model, adjusting for demographic and clinical factors. Resistance profiles were described in those with baseline and follow-up genotypes., Results: For 653 patients, distribution of third-agent use and viremia was: 244 (37%) on PIs with 80 viremia, 364 (56%) on NNRTIs with 84 viremia, and 45 (7%) on II with 11 viremia. Only for NNRTIs, time to viremia was longer than PIs (p = 0.04) for patients with a CD4 count ≥200 cells/mm(3). Of the 175 with viremia, 143 (82%) had baseline and 37 (21%) had follow-up genotype. Upon viremia, emerging ART resistance was rare. One new NNRTI (Y181C) mutation was identified and three patients taking PI-based regimens developed NRTI mutations (M184 V, M184I, and T215Y)., Conclusions: Time to viremia for NNRTIs was longer than PIs. With viremia, ART resistance rarely developed without PI or II mutations, but with a few NRTI mutations in those taking PI-based regimens, and NNRTI mutations in those taking NNRTI-based regimens.

Complex historical and cultural factors have contributed to the HIV epidemic among Aboriginal populations in Canada. This study assesses social supports, adaptive and maladaptive coping mechanisms, stress, and mastery of Canadian-born Aboriginal and Canadian-born Caucasian people living with HIV in Ontario and posits that coping and social support are important micro- and meso-level factors associated with the epidemic. This cross-sectional analysis included questionnaire data collected from 2007 to 2011 at HIV clinics in Toronto. Categorical and continuous variables were compared using chi-square and Wilcoxon rank sum tests, respectively. Correlates of social support and coping were determined using univariate and multivariable linear regression. The analysis included 70 Aboriginal and 665 Caucasian participants. Aboriginal participants had lower levels of employment, education, and annual household income. Aboriginal participants reported more overall (7 vs. 4, p = 0.0003), ongoing (4 vs. 2, p = 0.0004), and early childhood (2 vs. 1, p = 0.02) stressors. Maladaptive coping, adaptive coping, and mastery scores were similar between Aboriginal and Caucasian participants. In multivariable analysis, injection drug use and lower education levels were significant correlates of higher maladaptive coping and lower overall support scores. Despite numerous socioeconomic challenges and personal stressors, Aboriginal people living with HIV who are accessing care exhibited comparable coping and mastery scores to Canadian-born Caucasian people living with HIV, suggesting remarkable strengths within Aboriginal people living with HIV and their communities.

This study investigates the differences in severity and correlates of depression symptoms among 1069 men and 267 women living with HIV in Ontario, Canada, who completed the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Women had higher CES-D scores than that of men (median [interquartile range]: 13 [5-26] versus 9 [3-20], P=.0004). More women had total CES-D scores>15 (mild-moderate depression; 44% versus 33%, P=.002) and >21 (severe depression; 31% versus 23%, P=.003). Unlike men, at age 40, women's scores increased yearly (0.4 per increased year, P=.005). The distribution of scores differed by gender: There was no difference in the 10th percentile of depression scores, 0 (95% confidence interval [CI]: 1.0-1.0) but the 75th percentile of depression scores for women was 6 (95% CI: 2.0-10.0) points higher than that of men. Important gender differences exist in depression symptoms and in correlates of symptoms in people living with HIV., (© The Author(s) 2014.)

Background: The Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) engaged in an innovative community-based survey development process., Objectives: We sought to provide 1) an overview of the survey development process, and 2) personal reflections from women living with human immunodeficiency virus (HIV; "peers") on their own observations of strengths and short-comings of the process and opportunities for improvement., Methods: Guided by the principles of community-based research (CBR) and meaningful involvement of women living with HIV (WLWH), CHIWOS coordinated a national, multidisciplinary research team, and facilitated a community based survey development process., Lessons Learned: Four key lessons emerged highlighting the importance of 1) accommodating different preferences for feedback collection, 2) finding the right combination of people and skills, 3) formalizing mentorship, and 4) creating guidelines on survey item reduction and managing expectations from the outset., Conclusions: Peers discussed the strengths and weaknesses of participatory methodologies in survey development.

Background: Ensuring that people living with HIV are accessing and staying in care is vital to achieving optimal health outcomes including antiretroviral therapy (ART) success. We sought to characterize engagement in HIV care among participants of a large clinical cohort in Ontario, Canada, from 2001 to 2011., Methods: The Ontario HIV Treatment Network Cohort Study (OCS) is a multisite HIV clinical cohort, which conducts record linkage with the provincial public health laboratory for viral load tests. We estimated the annual proportion meeting criteria for being in care (≥1 viral load per year), in continuous care (≥2 viral load per year ≥90 days apart), on ART, and with suppressed viral load <200 copies per milliliter. Ratios of proportions according to socio-demographic and clinical characteristics were examined using multivariable generalized estimating equations with a log-link., Results: A total of 5380 participants were followed over 44,680 person-years. From 2001 to 2011, we observed high and constant proportions of patients in HIV care (86.3%-88.8%) and in continuous care (76.4%-79.5%). There were statistically significant rises over time in the proportions on ART and with suppressed viral load; by 2011, a majority of patients were on ART (77.3%) and had viral suppression (76.2%). There was minimal variation in HIV engagement indicators by socio-demographic and HIV risk characteristics., Conclusions: In a setting with universal health care, we observed high proportions of HIV care engagement over time and an increased proportion of patients attaining successful virologic suppression, likely due to improvements in ART regimens and changing guidelines.

Introduction: The resistance profiles of first-line antiretroviral therapy (ART) regimens after virologic failure have yet to be studied in a clinic setting in the modern treatment era. Time to virologic failure among three standard first-line regimens and the resistance profiles of these failures were compared., Materials and Methods: All HIV-positive persons aged 16 and over starting a three-drug first-line ART regimen were retrospectively identified at a Toronto community clinic (1 January 2006-1 January 2013). The regimens included a backbone of two NRTIs and a third agent; a PI, an NNRTI, or an II. Patients must have been on treatment for at least 14 days and have at least one VL test within 6 months after starting treatment. The primary outcome was virologic failure defined as either: no suppression by 6 months, or after suppression, two consecutive, detectable VL200 copies/mL at least 14 days apart or one VL>200 copies/mL. Time to failure was compared using a proportional hazards model adjusting for demographic and clinical factors. Resistance profiles of NRTIs and third agents are described in patients with virologic failure who had both baseline and virologic failure genotypes., Results: Six hundred sixty patients (93% male) were included with a mean age of 38.9 and a median follow-up period of 35.3 (32.2-39.3) months. Distribution of third agent use was: PI 37.3% (n=246), NNRTI 55.9% (n=369) and II 6.8% (n=45). Virologic failures occurred in 81/246 (33%) with PI, 87/369 (24%) with NNRTI and 11/45 (24%) with II. Compare to PIs, time to failure was longer with NNRTIs (p=0.0013) and similar for IIs (p=0.1562). No evidence that failure with NNRTIs was different from IIs (p=0.9139). Of the 660 patients, 567 (86%) had a baseline genotype. Of the 567 patients, 179 had virological failure. Of the 179, 145(81%) had a baseline genotype and only 37 (21%) had both a baseline and follow-up genotype. Upon failure, emerging ART resistance was rare. No new PI or II mutations were identified and one new NNRTI (Y181C) mutation was identified. Three patients taking PI-based regimens developed NRTI mutations (M184V, M184I, T215Y)., Conclusions: Time to virologic failure was significantly greater in the NNRTI group compared to the PI group. If failure did occur, ART resistance rarely developed with no PI mutations but a few NRTI mutations in those taking PI-based regimens, and NNRTI mutations in those taking NNRTI-based regimen.

The concept of psychological distress includes a range of emotional states with symptoms of depression and anxiety and has yet to be reported in HIV-positive women living in Ontario, Canada, who are known to live with contributing factors. This study aimed to determine the prevalence, severity, and correlates of psychological distress among women accessing HIV care participating in the Ontario HIV Treatment Network Cohort Study using the Kessler Psychological Distress Scale (K10). The K10 is a 10-item, five-level response scale. K10 values range from 10 to 50 with values less than or equal to 19 categorized as not clinically significant, scores between 20 and 24 as moderate levels, 25-29 as high, and 30-50 as very high psychological distress. Correlates of psychological distress were assessed using the Pearson's chi-square test and univariate and multivariate logistic regression analysis. Moderate, high, and very high levels of psychological distress were experienced by 16.9, 10.4, and 15.1% of the 337 women in our cohort, respectively, with 57.6% reporting none. Psychological distress levels greater than 19, correlated with being unemployed (vs. employed/student/retired; AOR = 0.33, 95% CI: 0.13-0.83), living in a household without their child/children (AOR = 2.45, 95% CI: 1.33-4.52), CD4 counts < 200 cells/mm(3) (AOR = 2.07, 95% CI: 0.89-4.80), and to a lesser degree an education of some college or less (vs. completed college or higher; AOR=1.71, 95% CI: 0.99-2.95). Age and ethnicity, a priori variables of interest, did not correlate with psychological distress. Findings suggest that socioeconomic factors which shape the demography of women living with HIV in Ontario, low CD4 counts, and losing the opportunity to care for their child/children has a significant relationship with psychological distress. Approaches to manage psychological distress should address and make considerations for the lived experiences of women since they can act as potential barriers to improving psychological well-being.

Background: CD8 T lymphocytes from chronically infected HIV-positive patients degenerate into a preapoptotic state and exhibit impaired functionality. Particularly in viremic patients, this was associated with an increased proportion of interleukin-7 receptor-alpha low-expressing (IL-7Ralpha(low)) effector-like CD8 T cells. As cytokine signaling through signal transducers and activators of transcription (STAT) is essential for cellular function, we hypothesized that activation of this pathway may be impaired in these cells., Objectives: To evaluate cytokine-induced STAT activation in IL-7Ralpha(low) and IL-7Ralpha(high) CD8 T cells from chronically infected HIV-positive patients and investigate the potential molecular mechanism involved in the reduced IL-7Ralpha expression., Methods: CD8 T cells from HIV-positive patients on and off antiretroviral therapy were assayed respectively for STAT activation, cytokine receptor, and transcription factor expression by flow cytometry and real-time PCR., Results: IL-7 stimulation failed to activate STAT5 in a substantial proportion of patient CD8 T cells. This correlated with reduced IL-7Ralpha mRNA and surface protein expression. Interestingly, IL-7Ralpha(low) cells appeared to be fully capable of recruiting the STAT pathway in response to IL-2, IL-4, IL-10, and IL-15. mRNA expression suggested a potential role for growth factor independent (Gfi)-1 as an IL-7Ralpha transcriptional repressor, but not that of other transcriptional regulators studied, including Gfi-1B and GA-binding protein alpha. Programmed death-1 inhibitory receptor, though upregulated in CD8 T cells from HIV-positive patients, appeared unrelated to IL-7Ralpha expression and STAT signaling capacity.

Respiratory syncytial virus (RSV) is a leading cause of respiratory disease among infants, the elderly and immunocompromised adults. In this study, we assessed the effects of alpha-galactosylceramide, a known immunoregulatory lipid, on liposomal RSV vaccine-induced responses in BALB/c mice subsequently challenged with RSV. Liposomes containing a recombinant fragment of the RSV G protein were prepared with and without alpha-galactosylceramide and used to immunize mice by the intranasal route. The inclusion of alpha-galactosylceramide in the liposomal formulation caused a dramatic reduction in bronchoalveolar lavage neutrophils, but also an increase in eosinophils, following subsequent RSV challenge. The reduction in neutrophils was specific to mice receiving alpha-galactosylceramide-containing liposomes and was not reproduced in mice administered liposomes containing another alpha-galactosyl lipid, alpha-galactosylphosphatidylglyceroylalkylamine. Lung IL-13 mRNA levels were particularly elevated in mice administered alpha-galactosylceramide-containing liposomes followed by RSV challenge. This study demonstrates a striking ability of alpha-galactosylceramide to modulate the cellular airway infiltrate in mice immunized with liposomal RSV vaccine followed by RSV challenge.

Human papillomavirus (HPV)-induced cervical cancer is the second most common cancer among women worldwide with half a million new cases per year. Despite the encouraging development of a preventive vaccine for HPV, a therapeutic vaccine for cervical cancer or pre-cancerous lesions remains a high priority. The preclinical study reported here used VacciMax((R)) (VM) to deliver a peptide-based vaccine composed of an HPV 16 E7-derived cytotoxic T lymphocyte (CTL) epitope fused to the T helper epitope PADRE (FP) and combined with CpG or lipopeptide adjuvant. In the study, C57BL/6 mice received 0.5million HPV 16-expressing C3 tumor cells. Mice were inoculated post-tumor challenge with a single s.c. injection of FP-CpG-VM on either day 4, 5, 6, 9, or 14. All mice that received the FP-CpG-VM vaccine were tumor-free to day 130 when the experiment was terminated. In contrast, only a minority of mice that received a control vaccine were tumor-free on day 60. Cytotoxicity assays, ELISPOT and intracellular staining for interferon (IFN)-gamma showed the immune response was specific for the selected CTL epitope. All mice that received the FP-CpG-VM vaccine remained tumor-free when re-challenged with 6million C3 cells. Cytotoxicity assays 4 months post-challenge showed that only splenocytes from mice inoculated with the FP-CpG-VM vaccine had high lysis activity. These results indicate that VacciMax((R)) causes a rapid, robust, durable and therapeutic CTL response to HPV 16 E7 protein expressing tumors.