Adverse drug reactions attributed to generic substitution of antiretroviral medications among HIV treatment and pre-exposure prophylaxis clients in British Columbia, Canada.

BACKGROUND: In British Columbia, antiretrovirals (ARVs) for HIV treatment (HIV-Tx) and pre-exposure prophylaxis (PrEP) are free-of-charge through publicly-funded Drug Treatment Programs (DTPs). When available, less costly generics are substituted for brand-name ARVs. We describe the incidence and type of product substitution issue (PSI) adverse drug reactions (ADRs) attributed to generic ARVs. METHODS: Cohorts included DTP clients ≥19 years who received generic ARVs for HIV-Tx (abacavir-lamivudine, emtricitabine-tenofovir DF, efavirenz-emtricitabine-tenofovir DF, atazanavir or darunavir between 01 Jun 2017 and 30 Jun 2022) or PrEP (emtricitabine-tenofovir DF, 01 Apr 2018 to 30 Jun 2022). Demographic, ARV and ADR data were extracted from DTP databases and summarized by descriptive statistics. PSI incidence was calculated for each product during the year following brand-to-generic and generic-to-generic transitions (first-year-post-rollout), and compared between generic versions using generalized estimating equations. For context, incidence of any ARV product-related ADR was calculated in the same 1-year periods. RESULTS: During first-year-post-rollout periods, 5339 HIV-Tx (83% male, median age 52 years) and 8095 PrEP (99% male, median 33 years) clients received generic ARVs, and reported 78 and 23 generic PSIs, respectively. PSI incidence was <1% for most generic ARVs, with mild-moderate symptoms including gastrointestinal upset, headache, dizziness, fatigue/malaise and skin rash. In HIV-Tx clients, the efavirenz-containing product had higher PSI incidence than other ARVs (2.2%, p = .004), due to more neuropsychiatric adverse reactions. Any ADR incidence was stable across measurement periods, and generic PSIs represented less than one third of all product-related ADRs. CONCLUSIONS: Generic substitution of antiretrovirals for HIV-Tx and PrEP was well tolerated, with ≤2% incidence of mild-moderate PSI ADRs.

Dynamics of overdose and non-overdose mortality among people living with HIV amidst the illicit drug toxicity crisis in British Columbia.

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.

It's all about connection: Determinants of social support and the influence on HIV treatment interruptions among people living with HIV in British Columbia, Canada.

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.

Identification of people with low prevalence diseases in administrative healthcare records: A case study of HIV in British Columbia, Canada.

INTRODUCTION: Case-finding algorithms can be applied to administrative healthcare records to identify people with diseases, including people with HIV (PWH). When supplementing an existing registry of a low prevalence disease, near-perfect specificity helps minimize impacts of adding in algorithm-identified false positive cases. We evaluated the performance of algorithms applied to healthcare records to supplement an HIV registry in British Columbia (BC), Canada. METHODS: We applied algorithms based on HIV-related diagnostic codes to healthcare practitioner and hospitalization records. We evaluated 28 algorithms in a validation sub-sample of 7,124 persons with positive HIV tests (2,817 with a prior negative test) from the STOP HIV/AIDS data linkage-a linkage of healthcare, clinical, and HIV test records for PWH in BC, resembling a disease registry (1996-2020). Algorithms were primarily assessed based on their specificity-derived from this validation sub-sample-and their impact on the estimate of the total number of PWH in BC as of 2020. RESULTS: In the validation sub-sample, median age at positive HIV test was 37 years (Q1: 30, Q3: 46), 80.1% were men, and 48.9% resided in the Vancouver Coastal Health Authority. For all algorithms, specificity exceeded 97% and sensitivity ranged from 81% to 95%. To supplement the HIV registry, we selected an algorithm with 99.89% (95% CI: 99.76% - 100.00%) specificity and 82.21% (95% CI: 81.26% - 83.16%) sensitivity, requiring five HIV-related healthcare practitioner encounters or two HIV-related hospitalizations within a 12-month window, or one hospitalization with HIV as the most responsible diagnosis. Upon adding PWH identified by this highly-specific algorithm to the registry, 8,774 PWH were present in BC as of March 2020, of whom 333 (3.8%) were algorithm-identified. DISCUSSION: In the context of an existing low prevalence disease registry, the results of our validation study demonstrate the value of highly-specific case-finding algorithms applied to administrative healthcare records to enhance our ability to estimate the number of PWH living in BC.

Identifying Longitudinal CD4:CD8 Ratio Trajectories Indicative of Chronic Renal Disease Risk among People Living with HIV: An Application of Growth Mixture Models.

The incidence of chronic kidney disease (CKD) is increasing among people living with HIV (PLWH). Routine monitoring of indicators such as CD4:CD8 ratio might improve the early detection of CKD. Our objective was to identify clinically relevant CD4:CD8 ratio trajectories indicative of CKD risk. Participants were ≥ 18 years old, initiated antiretroviral therapy between 2000 and 2016, and were followed for ≥6 months until 31 March 2017 or last contact date. Outcome was incidence of CKD. Growth mixture models (GMMs) and decay models were used to compare CD4:CD8 ratio trajectories. Following GMM, 4547 (93.5%) participants were classified in Class 1 with 5.4% developing CKD, and 316 (6.5%) participants were classified in Class 2 with 20.9% developing CKD. The final model suggested that participants in Class 2 had 8.72 times the incidence rate of developing CKD than those in Class 1. Exponential decay models indicated a significant CD4:CD8 ratio decline among Class 2 participants who developed CKD. Among those who developed CKD in Class 2, starting at 5.5 years of follow-up, the slope of their ratio trajectory curve changed significantly, and the rate of decline increased dramatically. Routine monitored CD4:CD8 ratios can be an effective strategy to identify early CKD risk among PLWH.

Associations between psychosocial factors and antiretroviral therapy outcomes differ by gender and sexual orientation among people living with HIV in British Columbia, Canada.

Little is known about how the co-occurrence of psychosocial factors affect sub-populations of people living with HIV (PLWH). We used cross-sectional data from 999 PLWH, aged ≥19, accessing antiretroviral therapy (ART) in British Columbia, Canada (2007-2010) to examine associations between psychosocial factors and ART-related outcomes separately for trans/cis inclusive women; heterosexual men; and gay, bisexual, and other men who have sex with men (gbMSM). Multivariable logistic regression examined associations between psychosocial factors (0-3): any violence in the past 6 months, depressive symptoms in the past week, and current street drug use (heroin, crack, meth or speedball) with sub-optimal adherence (outcome 1: average annual ART adherence <95% from interview until end of follow-up, death, or December 31st, 2018) and ever viral rebound (outcome 2) adjusting for potential confounders. Of 999 PLWH (264 women, 382 heterosexual men, and 353 gbMSM), women and heterosexual men had significantly higher median counts than gbMSM. Overall, higher counts were associated with sub-optimal adherence (adjusted odds ratio [aOR] = 1.26/1-unit increase, 95%CI = 1.07-1.49). All effect estimates were of a greater magnitude among gbMSM, but not significant for women or heterosexual men, highlighting the need for population (e.g., gender and sexual orientation)-centered care and research.

Causal and Associational Language in Observational Health Research: A Systematic Evaluation.

We estimated the degree to which language used in the high-profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases imply causality. We searched for and screened 1,170 articles from 18 high-profile journals (65 per journal) published from 2010-2019. Based on written framing and systematic guidance, 3 reviewers rated the degree of causality implied in abstracts and full text for exposure/outcome linking language and action recommendations. Reviewers rated the causal implication of exposure/outcome linking language as none (no causal implication) in 13.8%, weak in 34.2%, moderate in 33.2%, and strong in 18.7% of abstracts. The implied causality of action recommendations was higher than the implied causality of linking sentences for 44.5% or commensurate for 40.3% of articles. The most common linking word in abstracts was "associate" (45.7%). Reviewers' ratings of linking word roots were highly heterogeneous; over half of reviewers rated "association" as having at least some causal implication. This research undercuts the assumption that avoiding "causal" words leads to clarity of interpretation in medical research.

Evolving patterns of antiretroviral drug interactions in people with HIV in British Columbia, Canada.

OBJECTIVES: To characterize the annual prevalence of antiretroviral/nonantiretroviral drug interactions in relation to antiretroviral therapy (ART)-prescribing patterns, and to describe drug interaction-related ART changes. DESIGN/METHODS: This cohort study included ART-treated adults in British Columbia, Canada between 01 January 2010 and 31 December 2016. Medication dispensing records were abstracted from a population-based, linked administrative-health dataset and used to identify antiretroviral-comedication drug interactions ('caution'/'avoid' drug interactions in HIV-focused drug interaction checkers). We identified temporal trends in annual drug interaction prevalence and quantified the association between taking higher drug interaction-risk ART and receiving nonrecommended antiretroviral-comedication combinations using Poisson regression models, modified for binary outcomes and correlated data. Clinician-reported, drug interaction-related ART changes and associated adverse events were abstracted from an HIV drug treatment registry and summarized descriptively. RESULTS: Among 8571 ART-treated adults who received nonantiretroviral comedications, prevalence of having any drug interaction or receiving nonrecommended drug combination(s) significantly declined from 85 to 71% and 5.6 to 3.2%, respectively, between 2010 and 2016 ( P  < 0.001). This paralleled a shift from higher drug interaction-risk ART (e.g. ritonavir/cobicistat-boosted protease inhibitors) to lower drug interaction-risk ART (e.g. unboosted integrase inhibitors). Risk of receiving a nonrecommended antiretroviral-comedication combination was greater for persons taking higher vs. lower drug interaction-risk ART [adjusted risk ratio (aRR) 3.12, 95% confidence interval (CI) 2.24-4.35]. Boosted antiretroviral-inhaled corticosteroid drug interactions accounted for the most commonly dispensed, nonrecommended drug combinations, and the most commonly reported drug interaction-related adverse events (adrenal insufficiency). CONCLUSION: The prevalence of antiretroviral-comedication drug interactions is declining as ART shifts towards antiretrovirals with lower drug interaction potential but nonrecommended drug combinations remain a concern. Healthcare providers should screen for drug interactions whenever drugs are prescribed or dispensed.

Neighbourhood-level material deprivation and response to combination antiretroviral therapy in the Canadian Observational Cohort (CANOC): a longitudinal cohort study.

BACKGROUND: Socioeconomic status has been associated with higher viral loads and lower CD4 cell counts among people living with HIV. The objective of this study was to evaluate the relation between neighbourhood-level material deprivation and immunologic and virologic response to combination antiretroviral therapy (ART) among people living with HIV in Canada. METHODS: The Canadian Observational Cohort (CANOC) is a longitudinal cohort of people living with HIV, containing data from 2000-2016 from 5 Canadian provinces. We defined response to combination ART as positive if the CD4 cell count increased by 50 cells/mm3 (0.05 cells × 109/L) or more (CD4+) and viral load decreased to 50 copies/mL or less (VL+) within 6 months of treatment initiation. We further categorized response to therapy as concordant positive (CD4+/VL+), concordant negative (CD4-/VL-) or discordant (CD4+/VL- or CD4-/VL+). We used adjusted multinomial logistic regression to quantify the relation between neighbourhood-level material deprivation and immunologic and virologic response. RESULTS: This study included 8274 people living with HIV, of which 1754 (21.2%) lived in the most materially deprived neighbourhoods. Most individuals (62.2%) showed a concordant positive response to combination ART. After adjustment, living in the most materially deprived neighbourhoods was associated with a CD4-/VL+ discordant response (adjusted odds ratio [OR] 1.31, 95% confidence interval [CI] 1.06-1.62) and a concordant negative response (adjusted OR 1.45, 95% CI 1.13-1.86), using a concordant positive response as the reference. No other deprivation quartile was independently associated with a particular response. INTERPRETATION: People living with HIV from the most materially deprived neighbourhoods had increased odds of poor immunologic or virologic response to combination ART. These results motivate further study of the specific socioeconomic factors that potentially affect response to combination ART among people living with HIV in Canada.

The impact of lookback windows on the prevalence and incidence of chronic diseases among people living with HIV: an exploration in administrative health data in Canada.

BACKGROUND: We described the impact of different lengths of lookback window (LW), a retrospective time period to observe diagnoses in administrative data, on the prevalence and incidence of eight chronic diseases. METHODS: Our study populations included people living with HIV (N = 5151) and 1:5 age-sex-matched HIV-negative individuals (N = 25,755) in British Columbia, Canada, with complete follow-up between 1996 and 2012. We measured period prevalence and incidence of diseases in 2012 using LWs ranging from 1 to 16 years. Cases were deemed prevalent if identified in 2012 or within a defined LW, and incident if newly identified in 2012 with no previous cases detected within a defined LW. Chronic disease cases were ascertained using published case-finding algorithms applied to population-based provincial administrative health datasets. RESULTS: Overall, using cases identified by the full 16-year LW as the reference, LWs ≥8 years and ≥ 4 years reduced the proportion of misclassified prevalent and incidence cases of most diseases to < 20%, respectively. The impact of LWs varied across diseases and populations. CONCLUSIONS: This study underscored the importance of carefully choosing LWs and demonstrated data-driven approaches that may inform these choices. To improve comparability of prevalence and incidence estimates across different settings, we recommend transparent reporting of the rationale and limitations of chosen LWs.

Tobacco smoking and HIV-related immunologic and virologic response among individuals of the Canadian HIV Observational Cohort (CANOC).

We assessed the relationship between tobacco smoking and immunologic and virologic response among people living with HIV (PLWH) initiating combination antiretroviral therapy (cART) in the Canadian HIV Observational Cohort (CANOC). Positive immunologic and virologic response, respectively, were defined as ≥50 cells/mm3 CD4 count increase (CD4+) and viral suppression ≤50 copies/mL (VL+) within 6 months of cART initiation. Using multinomial regression, we examined the relationship between smoking, immunologic, and virologic response category. Model A adjusted for birth sex, baseline age, enrolling province, and era of cohort entry; models B and C further adjusted for neighbourhood level material deprivation and history of injection drug use (IDU), respectively. Among 4267 individuals (32.7%) with smoking status data, concordant positive (CD4+/VL+) response was achieved by 64.2% never, 66.9% former, and 59.4% current smokers. In the unadjusted analysis, current smoking was significantly associated with concordant negative response (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.40-2.45). Similarly, models A and B showed an increased odds of concordant negative response in current smokers (adjusted OR [aOR] 1.78, 95% CI 1.32-2.39 and 1.74, 95% CI 1.29-2.34, respectively). The association between current smoking and concordant negative response was no longer significant in model C (aOR 1.18, 95%CI 0.85-1.65).

Disparities in multimorbidity and mortality among people living with and without HIV across British Columbia's health regions: a population-based cohort study.

OBJECTIVES: Longer survival has increased the likelihood of antiretroviral-treated people living with HIV (PLWH) developing age-associated comorbidities. We compared the burden of multimorbidity and all-cause mortality across HIV status in British Columbia (BC), and assessed the longitudinal effect of multimorbidity on all-cause mortality among PLWH. METHODS: Antiretroviral-treated PLWH aged ≥19 years and 1:4 age-sex-matched HIV-negative individuals from a population-based cohort were followed for ≥1 year during 2001-2012. Diagnoses of seven age-associated comorbidities were identified from provincial administrative databases and grouped into 0, 1, 2, and ≥3 comorbidities. Multimorbidity prevalence and age-standardized mortality rates (ASMRs) in both populations were stratified by BC's health regions. Marginal structural models were used to estimate the effect of multimorbidity on mortality among PLWH, adjusted for time-varying confounders affected by prior multimorbidity. RESULTS: Among 8031 PLWH and 32,124 HIV-negative individuals, 25% versus 11% developed multimorbidity, and 23.53 deaths/1000 person-years (95% confidence interval [95% CI]: 22.02-25.13) versus 3.04 (2.81-3.29) were observed, respectively. PLWH in Northern region had the highest ASMR, but those in South Vancouver Island experienced the greatest difference in mortality compared with HIV-negative individuals. Among PLWH, compared with those with zero comorbidities, adjusted hazard ratios for those with 1, 2, and ≥3 comorbidities were 3.36 (95% CI: 2.86-3.95), 6.92 (5.75-8.33), and 12.87 (10.45-15.85), respectively. CONCLUSION: PLWH across BC's health regions experience excess multimorbidity and associated mortality. We highlight health disparities which are key when planning the distribution of healthcare resources across BC, and provide evidence for improved HIV care models integrating prevention and management of chronic diseases.

RéSUMé: OBJECTIF: Les nouvelles thérapeutiques antirétrovirales (ARV) ont permis une plus longue espérance de vie aux personnes porteuses du VIH. Cependant, le vieillissement augmente la probabilité de développer des comorbidités au sein même de la population des personnes vivant avec le VIH (PVVIH) qui suivent des traitements ARV. On a comparé le fardeau de la multimorbidité et mortalité, toutes causes confondues, lié au statut VIH à travers la Colombie-Britannique. On a aussi évalué l'effet longitudinal de la multimorbidité sur la mortalité, toutes causes confondues, parmi les PVVIH. MéTHODES: L'étude comprit des PVVIH suivant un traitement ARV âgés de ≥19 ans et un groupe témoin séronégatif (4 témoins par PVVIH) comparable en termes d'âge et de sexe, tous provenant d'une cohorte de surveillance continue d'au moins 1 an sur une période allant de 2001 à 2012. Des diagnostics de sept comorbidités liées à l'âge ont été identifiés à partir des bases de données administratives provinciales et regroupés en 0, 1, 2 et ≥3 comorbidités. La prévalence de la multimorbidité et les taux de mortalité normalisés selon l'âge (TMNA) dans les deux populations ont été stratifiés selon les régions sociosanitaires de la Colombie-Britannique. Des modèles structurels marginaux ont été utilisés pour estimer l'effet de la multimorbidité sur la mortalité chez les PVVIH, ajustant pour les facteurs de confusion variables affectés par une multimorbidité antérieure. RéSULTATS: Parmi 8 031 PVVIH et 32 124 personnes séronégatives pour le VIH, 25 % contre 11 % ont développé une multimorbidité et 23,53 décès pour 1 000 personnes-années (intervalle de confiance à 95 % [IC à 95 %]: 22,02­25,13) contre 3,04 (2,81­3,29) ont été observés, respectivement. Les PVVIH de la région septentrionale avaient le TMNA le plus élevé, alors que ceux du sud de l'île de Vancouver ont connu la plus grande différence de mortalité par rapport aux personnes séronégatives. Parmi les PVVIH, les personnes atteintes de 1, 2 et ≥3 comorbidités avaient respectivement 3,36 (IC à 95 %: 2,86­3,95), 6,92 (5,75­8,33) et 12,87 (10,45­15,85) fois plus la probabilité de mourir que les personnes sans comorbidités. CONCLUSION: Les PVVIH des régions sociosanitaires de la Colombie-Britannique connaissent une multimorbidité excessive et la surmortalité s'y associant. Notre étude souligne les disparités-clés en matière de santé qu'il faut prendre en compte lors de la planification de la distribution des ressources de soins de santé à travers la Colombie-Britannique. Elle fournit aussi des preuves pour des modèles de soins du VIH améliorés, y intégrant la prévention et la gestion des maladies chroniques.

Incidence of diabetes mellitus among people living with and without HIV in British Columbia, Canada between 2001 and 2013: a longitudinal population-based cohort study.

INTRODUCTION: People living with HIV (PLHIV) are increasingly at risk of age-related comorbidities such as diabetes mellitus (DM). While DM is associated with elevated mortality and morbidity, understanding of DM among PLHIV is limited. We assessed the incidence of DM among people living with and without HIV in British Columbia (BC), Canada, during 2001-2013. METHODS: We used longitudinal data from a population-based cohort study linking clinical data and administrative health data. We included PLHIV who were antiretroviral therapy (ART) naïve at baseline, and 1:5 age-sex-matched persons without HIV. All participants had ≥5 years of historic data pre-baseline and ≥1 year(s) of follow-up. DM was identified using the BC Ministry of Health's definitions applied to hospitalisation, physician billing and drug dispensation datasets. Incident DM was identified using a 5-year run-in period. In addition to unadjusted incidence rates (IRs), we estimated adjusted incidence rate ratios (IRR) using Poisson regression and assessed annual trends in DM IRs per 1000 person years (PYs) between 2001 and 2013. RESULTS: A total of 129 PLHIV and 636 individuals without HIV developed DM over 17 529 PYs and 88,672 PYs, respectively. The unadjusted IRs of DM per 1000 PYs were 7.4 (95% CI 6.2 to 8.8) among PLHIV and 7.2 (95% CI 6.6 to 7.8) for individuals without HIV. After adjustment for confounding, HIV serostatus was not associated with DM incidence (adjusted IRR: 1.03, 95% CI 0.83 to 1.27). DM incidence did not increase over time among PLHIV (Kendall trend test: p=0.9369), but it increased among persons without HIV between 2001 and 2013 (p=0.0136). CONCLUSIONS: After adjustment, HIV serostatus was not associated with incidence of DM, between 2001 and 2013. Future studies should investigate the impact of ART on mitigating the potential risk of DM among PLHIV.

Estimation of time of HIV seroconversion using a modified CD4 depletion model.

INTRODUCTION: Several methods have been proposed to estimate the time of HIV seroconversion, including those based on CD4 cell depletion models. However, previous models have failed to consider the heterogeneity that exists in CD4 trajectories among different sub-populations. Our objective was to estimate the time from HIV seroconversion relative to the HIV diagnosis date in a population-based cohort of people living with HIV (PLWH) in the province of British Columbia, Canada. METHODS: We used linked administrative and clinical data from the British Columbia Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort, which contains longitudinal individual-level data on all PLWH ever diagnosed in the province. Eligible participants were aged ≥18 years and diagnosed with HIV between 1989 and 2013. The outcome was pre-antiretroviral treatment CD4 cell count measurements assessed every six months. Models were stratified by age and stage of HIV infection at diagnosis. Several explanatory variables were considered including longitudinal viral load measurements. Longitudinal CD4, square root transformed, was modeled via a non-linear mixed effects model; time was modeled using an exponential decay function. We assumed a Gaussian distribution (identity link), an AR(1) correlation structure, and a random intercept and slope for the longitudinal viral load measurements. Due to the population variation in CD4 count among uninfected individuals, we assumed 500 to 1500 cells/mm3 as the normal range when estimating the time of HIV seroconversion. RESULTS: Longitudinal data on 1,253 individuals were analysed: 80% male, 33% White, and the median age at diagnosis was 38 years (25th-75th percentile [Q1-Q3], 31 to 45). CD4 decay differed by stage of infection at diagnosis and age, with those ≥50 years in Stages 1 and 2 experiencing a faster decline in CD4 over time. The median duration of infection from seroconversion until HIV diagnosis was 6.9 (Q1-Q3, 3.9 to 10.1) years. CONCLUSIONS: Considering the heterogeneity that exists in individual CD4 cell trajectories in a population, we presented a methodology that only relies on routinely collected HIV-related data, which can be further extended to estimate other epidemic measures.

Excess burden of age-associated comorbidities among people living with HIV in British Columbia, Canada: a population-based cohort study.

OBJECTIVES: As people living with HIV (PLWH) live longer, morbidity and mortality from non-AIDS comorbidities have emerged as major concerns. Our objective was to compare prevalence trends and age at diagnosis of nine chronic age-associated comorbidities between individuals living with and without HIV. DESIGN AND SETTING: This population-based cohort study used longitudinal cohort data from all diagnosed antiretroviral-treated PLWH and 1:4 age-sex-matched HIV-negative individuals in British Columbia, Canada. PARTICIPANTS: The study included 8031 antiretroviral-treated PLWH and 32 124 HIV-negative controls (median age 40 years, 82% men). Eligible participants were ≥19 years old and followed for ≥1 year during 2000 to 2012. PRIMARY AND SECONDARY OUTCOME MEASURES: The presence of non-AIDS-defining cancers, diabetes, osteoarthritis, hypertension, Alzheimer's and/or non-HIV-related dementia, cardiovascular, kidney, liver and lung diseases were identified from provincial administrative databases. Beta regression assessed annual age-sex-standardised prevalence trends and Kruskal-Wallis tests compared the age at diagnosis of comorbidities stratified by rate of healthcare encounters. RESULTS: Across study period, the prevalence of all chronic age-associated comorbidities, except hypertension, were higher among PLWH compared with their community-based HIV-negative counterparts; as much as 10 times higher for liver diseases (25.3% vs 2.1%, p value<0.0001). On stratification by healthcare encounter rates, PLWH experienced most chronic age-associated significantly earlier than HIV-negative controls, as early as 21 years earlier for Alzheimer's and/or dementia. CONCLUSIONS: PLWH experienced higher prevalence and earlier age at diagnosis of non-AIDS comorbidities than their HIV-negative controls. These results stress the need for optimised screening for comorbidities at earlier ages among PLWH, and a comprehensive HIV care model that integrates prevention and treatment of chronic age-associated conditions. Additionally, the robust methodology developed in this study, which addresses concerns on the use of administrative health data to measure prevalence and incidence, is reproducible to other settings.

Correlates of social isolation among people living with HIV in British Columbia, Canada.

Our study aims to define and identify correlates of social isolation among people living with HIV (PLHIV). The Longitudinal Investigation into Supportive and Ancillary health services (LISA) study provided a cross-sectional analytic sample of 996 PLHIV in British Columbia, Canada (sampled between 2007 and 2010). Individuals marginalized by socio-structural inequities were oversampled; sampling bias was addressed through inverse probability of participation weighting. Through latent class analysis, three groups were identified: Socially Connected (SC) (n = 364, 37%), Minimally Isolated (MI) (n = 540, 54%) and Socially Isolated (SI) (n = 92, 9%). Correlates of the SI and MI classes, determined through multivariable multinomial regression using the SC class as a reference, include: recent violence (aOR 1.61, 95%CI 1.28-2.02 [MI vs. SC]; aOR 2.04, 95%CI 1.41-2.96 [SI vs. SC]) and a mental health diagnosis (aOR 1.50, 95% CI 1.31-1.72 [MI vs. SC]; aOR 1.43, 95%CI 1.11-1.83 [SI vs. SC]). Women (aOR 0.47; 95%CI 0.32-0.68 [SI vs. SC]), individuals of Indigenous ancestry (aOR 0.59; 95%CI 0.40-0.87 [SI vs. SC]) and people identifying as gay or lesbian (aOR 0.37; 95%CI 0.26-0.52 [SI vs. SC]) were less likely to experience isolation. These findings highlight the importance of supporting communities fostering connectedness and identifies populations susceptible to isolation.

Social Isolation and Mortality Among People Living with HIV in British Columbia, Canada.

Social isolation, a risk factor for poor health within the general population, may be exacerbated by unique challenges faced by people living with HIV (PLHIV). This analysis examines the association between social isolation and all-cause mortality among a cohort of PLHIV experiencing multiple social vulnerabilities. The analytical sample included 936 PLHIV ≥ 19 years, living in British Columbia, Canada, and enrolled in the Longitudinal Investigation into Supportive and Ancillary Health Services (LISA) Study (2007-2010). Participants were classified as Socially Connected (SC), Minimally Isolated (MI) or Socially Isolated (SI) via latent class analysis. Cross-sectional survey data was linked to longitudinal clinical data from a provincial HIV treatment database. Mortality was assessed longitudinally up to and including December 31st, 2017. Through multivariable logistic regression, an association between SI and all-cause mortality was found (adjusted OR: 1.48; 95% CI 1.08, 2.01). These findings emphasize the need to mitigate effects of social isolation among PLHIV.

Severe intimate partner violence is associated with all-cause mortality among women living with HIV.

OBJECTIVE: To examine the independent association between intimate partner violence (IPV) severity and all-cause mortality among women living with HIV (WLHIV). DESIGN: Cross-sectional questionnaire linked to longitudinal vital statistics data. METHODS: We examined the lifetime prevalence of IPV and age-standardized all-cause mortality rates by IPV severity reported by WLHIV. Lifetime IPV (emotional/verbal, physical, or sexual) severity was assessed as a categorical variable: no history of any IPV (none); experienced one or two forms of IPV (moderate); or experienced all three forms of IPV (severe IPV). Two separate logistic regression models examined associations between any IPV (vs. none) as well as IPV severity (none vs. moderate, severe) and all-cause mortality. RESULTS: At the time of interview (2007-2010), 260 participants self-identified as women with a median (Q1-Q3) age of 41 years (35-46). Of these women, the majority were unemployed (85%), 59% reported any IPV and 24% reported severe IPV. Of the 252 women followed until 31 December 2017, 25% (n = 63) died. Age-standardized all-cause mortality rates for WLHIV who experienced severe IPV were two-times higher than women with no history of IPV (44.7 per 1000 woman-years vs. 20.9 per 1000 woman-years). After adjustment for confounding, experiences of severe IPV (vs. none) were significantly associated with all-cause mortality (aOR = 2.42, 95% CI = 1.03-5.70). CONCLUSION: Although we found that any lifetime experience of IPV was not associated with all-cause mortality, women ever experiencing severe IPV were significantly more likely to die during the study period. This may suggest a need for increased trauma- and violence-aware approaches.

Loneliness and self-rated physical health among gay, bisexual and other men who have sex with men in Vancouver, Canada.

BACKGROUND: Due to stigma and discrimination, gay, bisexual and other men who have sex with men (gbMSM) potentially carry a heightened burden of loneliness. This analysis investigates loneliness among gbMSM and its relationship with self-rated physical health, along with the mediating effect of depression. METHODS: Participants were recruited using respondent-driven sampling into the Momentum Health Study (February 2012-February 2015) with follow-up visits occurring every 6 months till February 2018. Using computer-assisted self-interviews, measures of loneliness were assessed using a 6-item Loneliness Scale for Emotional and Social Loneliness (lonely vs not lonely). Current physical health was self-assessed (poor, fair, good, very good or excellent). A multivariable generalised linear-mixed model with a logit link function was used to examine the relationship between loneliness and self-rated physical health. We further investigated the mediating effect of depressive symptomatology on this relationship via the Hospital Anxiety and Depression Scale. RESULTS: Of the 770 participants included, we found that 61% (n=471) experienced loneliness at baseline. Of the 674 (88%) who reported good/very good/excellent physical health, 59% (n=391) reported loneliness, compared with 87% (n=80) of those in poor/fair self-rated physical health who reported feeling lonely. After adjustment for confounding, loneliness was associated with poor self-rated physical health (adjusted OR 1.71; 95% CI 1.13 to 2.60). Depressive symptomatology was found to partially mediate this relationship. CONCLUSION: There may be a need for the integration of social, mental and physical health programming, targeted towards gbMSM, to alleviate the degree of loneliness experienced and its co-occurrence with poor self-rated physical health.