Correction to: Factors Associated with Mood Disorder Diagnosis Among a Population Based Cohort of Men and Women Living With and Without HIV in British Columbia Between 1998 and 2012.

Using data from the Comparison of Outcomes and Service Utilization Trends (COAST) study we examined factors associated with mood disorder diagnosis (MDD) among people living with HIV (PLHIV) and HIV-negative individuals in British Columbia, Canada. MDD cases were identified between 1998 and 2012 using International Classification of Disease 9 and 10 codes. A total of 491,796 individuals were included and 1552 (23.7%) and 60,097 (12.4%) cases of MDD were identified among the HIV-positive and HIV-negative populations, respectively. Results showed HIV status was associated with greater odds of MDD among men and lower odds among women. Among PLHIV, MDD was significantly associated with: identifying as gay, bisexual or other men who have sex with men compared to heterosexuals; higher viral load; history of injection drug use; and concurrent anxiety, dysthymia, and substance use disorders. Findings highlight the need for comprehensive and holistic HIV and mental health care.

Substance Use, Violence, and Antiretroviral Adherence: A Latent Class Analysis of Women Living with HIV in Canada.

We used latent class analysis to identify substance use patterns for 1363 women living with HIV in Canada and assessed associations with socio-economic marginalization, violence, and sub-optimal adherence to combination antiretroviral therapy (cART). A six-class model was identified consisting of: abstainers (26.3%), Tobacco Users (8.81%), Alcohol Users (31.9%), 'Socially Acceptable' Poly-substance Users (13.9%), Illicit Poly-substance Users (9.81%) and Illicit Poly-substance Users of All Types (9.27%). Multinomial logistic regression showed that women experiencing recent violence had significantly higher odds of membership in all substance use latent classes, relative to Abstainers, while those reporting sub-optimal cART adherence had higher odds of being members of the poly-substance use classes only. Factors significantly associated with Illicit Poly-substance Users of All Types were sexual minority status, lower income, and lower resiliency. Findings underline a need for increased social and structural supports for women who use substances to support them in leading safe and healthy lives with HIV.

Factors Associated with Mood Disorder Diagnosis Among a Population Based Cohort of Men and Women Living With and Without HIV in British Columbia Between 1998 and 2012.

Using data from the Comparison of Outcomes and Service Utilization Trends (COAST) study we examined factors associated with mood disorder diagnosis (MDD) among people living with HIV (PLHIV) and HIV-negative individuals in British Columbia, Canada. MDD cases were identified between 1998 and 2012 using International Classification of Disease 9 and 10 codes. A total of 491,796 individuals were included and 1552 (23.7%) and 60,097 (12.4%) cases of MDD were identified among the HIV-positive and HIV-negative populations, respectively. Results showed HIV status was associated with greater odds of MDD among men and lower odds among women. Among PLHIV, MDD was significantly associated with: identifying as gay, bisexual or other men who have sex with men compared to heterosexuals; higher viral load; history of injection drug use; and concurrent anxiety, dysthymia, and substance use disorders. Findings highlight the need for comprehensive and holistic HIV and mental health care.

Mortality among people living with HIV/AIDS with non-small-cell lung cancer in the modern HAART Era.

People living with HIV (PLWHA) with adequate access to modern combination antiretroviral therapy (cART) are living longer and experiencing reduced AIDS-related morbidity and mortality. However, increases in non-AIDS related conditions, such as certain cancers, have accompanied these therapeutic advances over time. As such, our study objective was to determine the impact of HIV on all-cause and lung cancer-specific mortality amongst PLWHA with diagnoses of non-small-cell lung cancer (NSCLC) and HIV-negative individuals with NSCLC. This analysis was inclusive of PLWHA on and off cART over the age of 19 years and a 10% comparison sample from the BC population ≥19 years, over a 13-year period (2000-2013). Kaplan-Meier estimates, Cox PH models, and competing risk analysis for all-cause and cause-specific mortality (respectively) compared PLWHA to HIV-negative individuals, controlling for age, gender, cancer stage, co-morbidities; and nadir CD4 count, viral load, and injection drug use for a HIV-positive specific analysis. We identified 71 PLWHA and 2463 HIV-negative individuals diagnosed with NSCLC between 2000 and 2013. PLWHA with NSCLC were diagnosed at a significantly younger age than HIV-negative individuals (median age 57 vs 71 years, p < 0.01). We found no significant difference in lung cancer-specific mortality. However, in multivariate analysis, HIV was associated with greater all-cause mortality (adjusted hazard ratio [aHR]:1.44; 95% confidence interval [CI]: 1.08-1.90), with median survival of 4 months for PLWHA, and 10 months for HIV-negative. Higher nadir CD4 count was protective against mortality (aHR: 0.33, 95% CI: 0.17-0.64) amongst PLWHA in multivariate analysis. Our analysis suggests that PLWHA in the modern cART era experience similar lung cancer survival outcomes compared to the general BC population with NSCLC. However, we also observed significantly higher all-cause mortality among PLWHA with NSCLC, which may warrant further inquiry into the role of HIV in exacerbating mortality among PLWHA with comorbidities and cancer.

Transition from Pediatric to Adult HIV Care for Young Women Living with HIV.

Transitioning from pediatric to adult care is a complicated process for youth with chronic illnesses. This study elucidates the unique factors affecting transition preparedness and perception of adult HIV care among a cohort of young women with HIV. Between 2013 and 2015, 48 women with HIV, who had experience with pediatric HIV care, were enrolled in a large Canadian cohort study. Variables were self-reported during peer-administered surveys. Only 60% reported feeling prepared for transition. Having never had contact with child protection services (P = .049), never been in foster care (P = .011), never been in a group home (P = .036), reporting a higher current CD4 count (P = .033), and reporting a younger ideal age for transition (P = .041) were associated with transition preparedness. Eighty-four percent reported equivalent or better HIV care following transition. Correlates of equivalent/better care following transition included lower personal income (P = .023), higher CD4 count (P = .021), care by an adult infectious diseases specialist (P = .002), and transition preparedness (P = .005). Our findings highlight the importance of adequate transition preparation and its effect on perception of care following transition.

Prevalence and Correlates of Forced Sex as a Self-Reported Mode of HIV Acquisition Among a Cohort of Women Living With HIV in Canada.

Gender-based violence (GBV) is a global epidemic associated with increased HIV exposure. We assessed the prevalence and correlates of HIV acquisition via forced sex among women living with HIV (WLWH) in Canada. Baseline questionnaire data were analyzed for WLWH (≥16 years) with data on self-reported mode of HIV acquisition, enrolled in a community-based cohort study in British Columbia, Ontario, and Québec. We assessed forced sex (childhood, adulthood) as a self-reported mode of HIV acquisition. Of 1,330 participants, the median age was 42 (interquartile range [IQR] = 35-50) years; 23.5% were Indigenous, 26.3% African/Caribbean/Black, 43% White, and 7.2% of Other ethnicities. Forced sex was the third dominant mode of HIV transmission at 16.5% (n = 219; vs. 51.6% consensual sex, 19.7% sharing needles, 5.3% blood transfusion, 3.8% perinatal, 1.3% contaminated needles, 0.4% other, 1.6% do not know/prefer not to answer). In multivariable analyses, significant correlates of HIV acquisition from forced versus consensual sex included legal status as a landed immigrant (adjusted odds ratio [aOR] = 1.99; 95% confidence interval [CI] = [1.12, 3.54]) or refugee (aOR = 3.62; 95% CI = [1.63, 8.04]) versus Canadian citizen; African/Caribbean/Black ethnicity versus Caucasian (aOR = 2.49; 95% CI = [1.43, 4.35]), posttraumatic stress disorder symptoms (aOR = 3.00; 95% CI = [1.68, 5.38]), histories of group home residence (aOR = 2.40; 95% CI = [1.10, 5.23]), foster care (aOR = 2.18; 95% CI = [1.10, 4.34]), and having one child relative to having three or more children (aOR = 0.52; 95% CI = [0.31, 0.89]). GBV must be considered a distinct HIV risk factor; forced sex is a significant underrecognized risk factor and mode of women's HIV acquistion. Public health reporting systems can separate consensual and forced sex in reporting modes of HIV acquisition. Practitioners can engage in screening practices to meet client needs.

Pathways From HIV-Related Stigma to Antiretroviral Therapy Measures in the HIV Care Cascade for Women Living With HIV in Canada.

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 (ß = -0.104, P < 0.05) and current ART use (ß = -0.142, P < 0.01), and negative self-image to ART initiation (ß = -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.

Rates and predictors of injury in a population-based cohort of people living with HIV.

OBJECTIVES: Injuries are responsible for 10% of the global burden of disease; however, the epidemiology of injury among people living with HIV (PLHIV) has not been well elucidated. This study seeks to characterize rates and predictors of injury among PLHIV compared to the general population in British Columbia (BC), Canada. DESIGN: A population-based dataset was created via linkage between the BC Centre for Excellence in HIV/AIDS and PopulationDataBC. METHODS: PLHIV aged 20 years and older were compared to a random 10% sample of the adult general population. The International Classification of Diseases 9 and 10 codes were used to classify unintentional and intentional injuries based on the external cause of the injury from 1996 to 2013. Generalized estimating equation (GEE) Poisson regression models were fit to estimate the effect of HIV status on rates of unintentional and intentional injury, and to identify correlates of injury among PLHIV. RESULTS: The crude incidence rate of unintentional injury was 18.56/1000 person-years [95% confidence interval (CI) 17.77-19.39] among PLHIV and 8.51/1000 person-years (95% CI 8.42-8.59) in the general population. Among PLHIV, 13.45% of deaths were due to injury, compared to 5.52% of deaths in the general population. In adjusted models, PLHIV were more likely to report unintentional (incidence rate ratio 1.42, 95% CI 1.32-1.52) and intentional injury (incidence rate ratio 1.93, 95% CI 1.70-2.18) compared to the general population. CONCLUSIONS: We identified elevated rates of intentional and unintentional injury among PLHIV. Injuries are largely preventable; as such, targeted efforts are needed to decrease the burden of injury-related disability and death among PLHIV.

Health-adjusted life expectancy in HIV-positive and HIV-negative men and women in British Columbia, Canada: a population-based observational cohort study.

BACKGROUND: We sought to understand whether people living with HIV (PLHIV) ever on highly active antiretroviral therapy (ART) follow a pattern where morbidity is compressed into the last years of life or lessened as people age. We aimed to estimate health-adjusted life expectancy (HALE) among adults living with and without HIV, and examine dependency between causes of comorbidities. METHODS: The Comparative Outcomes and Service Utilization Trends (COAST) study is a retrospective cohort of adults (≥20 years) including all known PLHIV and a 10% random sample of the general population of British Columbia, and with longitudinal data spanning from April 1, 1996, to Dec 31, 2012. We determined the prevalence of select comorbidities (cardiovascular, respiratory, liver, and renal diseases, and non-AIDS defining cancers because of their high prevalence among PLHIV) by age and sex by use of case-finding algorithms. Deaths were obtained from a vital event registry from British Columbia, Canada. Comorbid-specific HALE was estimated from 20 years of age by HIV status and sex. For each comorbidity, a healthy state was defined as the proportion of life expectancy comorbid-free, and was adjusted on the probability of occurrence of other different comorbidities. The sensitivity of HALE estimates was assessed to the sequencing of select comorbidities for the dependent comorbidity adjustments. FINDINGS: Our sample consisted of electronic health records from 9310 HIV-infected and 510 313 uninfected adults over the period April 1, 1996, to Dec 31, 2012. These individuals contributed 49 605 deaths and 5 576 841 person-years over the study period. At exactly age 20 years, HALE was about 31 years (SD 0·16) among men living with HIV and 27 years (0·16) among women living with HIV. In the HIV-negative population, HALE was around 58 years (SD 0·02) for men and 63 years (0·02) for women. These results seem independent of ordering. However, PLHIV, particularly women living with HIV, had much shorter overall life expectancies than did their HIV-negative counterparts in the general population [29·1 years (SD 0·1) vs 65·4 years (0·1)], and thus spent less time in a healthy state. INTERPRETATION: Although we noted little differences in the levels of morbidity compression by HIV status, PLHIV-especially women living with HIV-spent less time in a healthy state. Expanded service delivery interventions to address complex care needs of ageing PLHIV are crucial to address shorter life expectancies, and improve their healthy states. FUNDING: Canadian Institutes of Health Research.

Pregnancy incidence and intention after HIV diagnosis among women living with HIV in Canada.

BACKGROUND: Pregnancy incidence rates among women living with HIV (WLWH) have increased over time due to longer life expectancy, improved health status, and improved access to and HIV prevention benefits of combination antiretroviral therapy (cART). However, it is unclear whether intended or unintended pregnancies are contributing to observed increases. METHODS: We analyzed retrospective data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS). Kaplan-Meier methods and GEE Poisson models were used to measure cumulative incidence and incidence rate of pregnancy after HIV diagnosis overall, and by pregnancy intention. We used multivariable logistic regression models to examine independent correlates of unintended pregnancy among the most recent/current pregnancy. RESULTS: Of 1,165 WLWH included in this analysis, 278 (23.9%) women reported 492 pregnancies after HIV diagnosis, 60.8% of which were unintended. Unintended pregnancy incidence (24.6 per 1,000 Women-Years (WYs); 95% CI: 21.0, 28.7) was higher than intended pregnancy incidence (16.6 per 1,000 WYs; 95% CI: 13.8, 20.1) (Rate Ratio: 1.5, 95% CI: 1.2-1.8). Pregnancy incidence among WLWH who initiated cART before or during pregnancy (29.1 per 1000 WYs with 95% CI: 25.1, 33.8) was higher than among WLWH not on cART during pregnancy (11.9 per 1000 WYs; 95% CI: 9.5, 14.9) (Rate Ratio: 2.4, 95% CI: 2.0-3.0). Women with current or recent unintended pregnancy (vs. intended pregnancy) had higher adjusted odds of being single (AOR: 1.94; 95% CI: 1.10, 3.42), younger at time of conception (AOR: 0.95 per year increase, 95% CI: 0.90, 0.99), and being born in Canada (AOR: 2.76, 95% CI: 1.55, 4.92). CONCLUSION: Nearly one-quarter of women reported pregnancy after HIV diagnosis, with 61% of all pregnancies reported as unintended. Integrated HIV and reproductive health care programming is required to better support WLWH to optimize pregnancy planning and outcomes and to prevent unintended pregnancy.

Cohort profile: The Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS).

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).

SNP-SNP interactions discovered by logic regression explain Crohn's disease genetics.

In genome-wide association studies (GWAS), the association between each single nucleotide polymorphism (SNP) and a phenotype is assessed statistically. To further explore genetic associations in GWAS, we considered two specific forms of biologically plausible SNP-SNP interactions, 'SNP intersection' and 'SNP union,' and analyzed the Crohn's Disease (CD) GWAS data of the Wellcome Trust Case Control Consortium for these interactions using a limited form of logic regression. We found strong evidence of CD-association for 195 genes, identifying novel susceptibility genes (e.g., ISX, SLCO6A1, TMEM183A) as well as confirming many previously identified susceptibility genes in CD GWAS (e.g., IL23R, NOD2, CYLD, NKX2-3, IL12RB2, ATG16L1). Notably, 37 of the 59 chromosomal locations indicated for CD-association by a meta-analysis of CD GWAS, involving over 22,000 cases and 29,000 controls, were represented in the 195 genes, as well as some chromosomal locations previously indicated only in linkage studies, but not in GWAS. We repeated the analysis with two smaller GWASs from the Database of Genotype and Phenotype (dbGaP): in spite of differences of populations and study power across the three datasets, we observed some consistencies across the three datasets. Notable examples included TMEM183A and SLCO6A1 which exhibited strong evidence consistently in our WTCCC and both of the dbGaP SNP-SNP interaction analyses. Examining these specific forms of SNP interactions could identify additional genetic associations from GWAS. R codes, data examples, and a ReadMe file are available for download from our website: http://www.ualberta.ca/~yyasui/homepage.html.