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.

Risk of Multiple Sclerosis in People Living with HIV: An International Cohort Study.

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

Characterizing opioid agonist therapy uptake and factors associated with treatment retention among people with HIV in British Columbia, Canada.

Accidental overdoses are now the leading cause of death among people with HIV (PWH) in British Columbia (BC). We examined the utilization and retention of opioid agonist therapy (OAT). Adult PWH (≥19 years) with ≥ 1 OAT dispensation in BC between 2008 and 2020 were included (n = 1,515). OAT treatment episodes were formed based on specific criteria for slow-release oral morphine (SROM), methadone, injectable OAT (iOAT), and buprenorphine/naloxone. Retention in treatment was defined as any episode lasting ≥ 12 months. Logistic regression with generalized estimating equations modeled retention-associated factors. There was a 56.6% decline in OAT retention over time. Buprenorphine treatment exhibited significantly lower odds of retention (OR: 0.58; 95% CI: 0.36-0.92) compared to methadone. Conversely, no significant change in retention odds was observed for SROM (0.72; 0.33-1.54) and iOAT (0.81; 0.31-2.12). Factors associated with increased odds of retention included a 10-year increase in age (1.69; 1.46-1.95), previous retention history (1.96; 1.40-2.73), achieving OAT therapeutic dose (8.22; 6.67-10.14), and suppressed HIV viral load (1.35; 1.10-1.67). Individuals with a lifetime HCV diagnosis receiving iOAT were more likely to retain (3.61; 1.20-10.83). Each additional year on OAT during the study period was associated with a 4% increase in the odds of retention. A significant proportion of PWH had a history of OAT prescribing but experienced low retention rates. Retention outcomes were more positive for SROM and iOAT. The association between OAT medication type and retention odds may be particularly influenced by HCV diagnosis. Optimal management of opioid use disorder among PWH, with an emphasis on attaining the therapeutic dose is crucial.

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.

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).

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.

Development of a computable phenotype to identify a transgender sample for health research purposes: a feasibility study in a large linked provincial healthcare administrative cohort in British Columbia, Canada.

OBJECTIVES: Innovative methods are needed for identification of transgender people in administrative records for health research purposes. This study investigated the feasibility of using transgender-specific healthcare utilisation in a Canadian population-based health records database to develop a computable phenotype (CP) and identify the proportion of transgender people within the HIV-positive population as a public health priority. DESIGN: The Comparative Outcomes and Service Utilization Trends (COAST) Study cohort comprises a data linkage between two provincial data sources: The British Columbia (BC) Centre for Excellence in HIV/AIDS Drug Treatment Program, which coordinates HIV treatment dispensation across BC and Population Data BC, a provincial data repository holding individual, longitudinal data for all BC residents (1996-2013). SETTING: British Columbia, Canada. PARTICIPANTS: COAST participants include 13 907 BC residents living with HIV (≥19 years of age) and a 10% random sample comparison group of the HIV-negative general population (514 952 individuals). PRIMARY AND SECONDARY OUTCOME MEASURES: Healthcare records were used to identify transgender people via a CP algorithm (diagnosis codes+androgen blocker/hormone prescriptions), to examine related diagnoses and prescription concordance and to validate the CP using an independent provider-reported transgender status measure. Demographics and chronic illness burden were also characterised for the transgender sample. RESULTS: The best-performing CP identified 137 HIV-negative and 51 HIV-positive transgender people (total 188). In validity analyses, the best-performing CP had low sensitivity (27.5%, 95% CI: 17.8% to 39.8%), high specificity (99.8%, 95% CI: 99.6% to 99.8%), low agreement using Kappa statistics (0.3, 95% CI: 0.2 to 0.5) and moderate positive predictive value (43.2%, 95% CI: 28.7% to 58.9%). There was high concordance between exogenous sex hormone use and transgender-specific diagnoses. CONCLUSIONS: The development of a validated CP opens up new opportunities for identifying transgender people for inclusion in population-based health research using administrative health data, and offers the potential for much-needed and heretofore unavailable evidence on health status, including HIV status, and the healthcare use and needs of transgender people.

Characteristics of older adults living with HIV accessing home and community care services in British Columbia, Canada.

Over half of people living with HIV (PLHIV) engaged in care in British Columbia (BC) are age ≥50. The public home and community care (HCC) system offers formal support that PLHIV may turn to as they age, but little is known about access specific to PLHIV. Using data from the STOP HIV/AIDS cohort, which includes linked treatment and demographic records for PLHIV accessing care in BC, we compared older PLHIV (defined as those age ≥50) who did and did not access HCC services. We estimated adjusted odds ratios (aORs) for factors associated with HCC service utilization using logistic regression. This study included 5,603 PLHIV age ≥50, 837 (14.94%) of whom accessed any HCC service between 2005 and 2015. Services most commonly used were community nursing (8.98%, n = 503) and rehabilitation (7.73%, n = 433). Those who received HCC were more likely to be female (aOR = 1.56, 95% CI = 1.24, 1.98), have a history of injection drug use (aOR = 1.88, 95% CI = 1.57, 2.25), have a higher Charlson comorbidity score (aOR = 1.11, 95% CI:1.07, 1.15) and to have visited a general practitioner in the past year (aOR = 2.17, 95% CI = 1.77, 2.67). Approximately 15% of older PLHIV have accessed HCC, but the extent of potential unmet need for these services requires further research.

Influence of the definition of rurality on geographic differences in HIV outcomes in British Columbia: a retrospective cohort analysis.

BACKGROUND: Improving rural health is often identified as a priority area for research and policy in Canada. We examined how findings on HIV outcomes (virologic suppression) can vary depending on the definition of rurality used. METHODS: We performed retrospective cohort analyses using the Comparative Outcomes and Service Utilization Trends study population-based cohort of adults (age ≥ 19 yr) living with HIV in British Columbia between Apr. 1, 2012, and Mar. 31, 2013. We performed univariate logistic regression analyses using the following geographic variables to predict HIV virologic suppression: rurality defined by forward sortation area, by Statistical Area Classification and by health authority. We mapped suppression using geographic information systems. RESULTS: Virologic suppression was observed in 5605 (65.2%) of 8598 participants. In univariate analysis, rurality defined by Statistical Area Classification (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.65-0.82), but not by forward sortation area, was associated with lower odds of suppression. When we examined suppression by health authority, Northern Health had the lowest odds of suppression (OR 0.46, 95% CI 0.36-0.58 compared to Vancouver Coastal Health). Geographic information systems mapping showed poorer suppression in northern areas. INTERPRETATION: Health outcome findings can vary depending on the definition of the geographic variable. When including geographic variables, researchers should carefully consider variable definitions and whether other classification systems, such as north-south, are more appropriate than rurality for their analysis.

The impact of high-dose opioid prescription on mortality rates among people living with HIV: A retrospective cohort study.

OBJECTIVES: High-dose opioid use is associated with increased morbidity, mortality, and healthcare utilization. People living with HIV (PLHIV) are frequently prescribed these medications to manage their pain. However, little is known about the relationship between being prescribed high doses of opioids (> 90 MME/d) and mortality risk among this population. The objective of this study was to examine the trends in mortality and the relationship between high-dose opioid analgesic prescribing and mortality among PLHIV. METHODS: Utilizing the STOP HIV/AIDS cohort--a population-level linked database of treatment of PLHIV in British Columbia--we conducted bivariable and multivariable generalized estimating equation (GEE) models with a Poisson distribution to examine the relationship between high-dose opioid prescription and all-cause mortality rates in the study sample. RESULTS: Between 1996 and 2015, 9272 PLHIV were included in the study. Age- and sex-adjusted mortality rate (using the 2011 Canadian population as the reference) was 30.99 per 1000 person-years (95% confidence interval [CI]: 28.11-33.88). In a multivariable GEE model with adjustment for various demographic and clinical confounders, there was a positive and independent association between being prescribed high-dose opioids and all-cause mortality rates (adjusted rate ratio [ARR] = 3.01; 95%CI: 2.47-3.66). DISCUSSION: We found that mortality rates were significantly higher among PLHIV who were prescribed high-dose opioids compared to those who were prescribed lower doses. Our results highlight the risk associated with the prescribing of high-dose opioids to manage HIV-related pain and emphasize the need to explore non-opioid approaches to pain management.

HIV, schizophrenia, and all-cause mortality: A population-based cohort study of individuals accessing universal medical care from 1998 to 2012 in British Columbia, Canada.

Schizophrenia is a severe mental illness with important implications for morbidity and mortality. This population-based cohort study examined the impact of schizophrenia diagnoses on all-cause mortality among a sample of people living with HIV (PLHIV) and a 10% random sample of individuals living without HIV (HIV-) in British Columbia (BC), through a data linkage between the BC Centre for Excellence in HIV/AIDS and Population Data BC's data holdings. Schizophrenia diagnoses were identified via International Classification of Diseases version 9 and version 10 codes. Age- and sex-adjusted all-cause mortality rates from January 1st, 1998 to December 31st, 2012 were calculated. Multivariable logistic models assessed (1) HIV status and mortality among individuals diagnosed with schizophrenia, (2) schizophrenia diagnosis and mortality among PLHIV, and (3) correlates of mortality among PLHIV concurrently diagnosed with schizophrenia (HIV+/SZO+). From 1998 to 2012, 6.3% of those with HIV had a schizophrenia diagnosis, compared to 1.1% of those without HIV. While significant declines in mortality rates were observed throughout the study period, mortality rates were highest among HIV+/SZO+. After adjustment for substance use disorder and age at baseline, HIV+/SZO+ had a 2.64 times greater odds of mortality (95% confidence interval [CI] = 2.14-3.25) compared to HIV-/SZO+. For PLHIV, a schizophrenia diagnosis was not associated with mortality after controlling for potential confounders (adjusted odds ratio [aOR] = 0.90, 95%CI = 0.74-1.09). Among HIV+/SZO+, age, history of injection drug use, ever having an AIDS-defining illness, and never being on anti-psychotic medication or accessing psychiatric services were associated with mortality. Efforts should be made to identify and link to care individuals disproportionately affected by schizophrenia and excess mortality, including those living with HIV.

Correlates of opioid and benzodiazepine co-prescription among people living with HIV in British Columbia, Canada: A population-level cohort study.

BACKGROUND: Co-prescribing benzodiazepines and opioids is relatively contraindicated due to the possible overdose risk. However, people living with HIV (PLWH) may have concurrent psychiatric and/or chronic pain diagnoses that may lead to the use of opioids and/or benzodiazepines for symptomatic treatment. Consequently, some PLWH may be at-risk for the health harms associated with the co-prescribing of these medications. Given this, the objectives of this study were to first examine the prevalence of opioids and benzodiazepines co-prescribing, and second, to characterize patient factors associated with the co-prescribing of opioids and benzodiazepines among PLWH in British Columbia (BC), Canada. METHODS: Using data derived from a longitudinal BC cohort, we used bivariable and multivariable generalized estimating equation models to establish the prevalence of a benzodiazepine and opioid co-prescription and determine factors associated with this practice. RESULTS: Between 1996 and 2015, 14 484 PLWH were included in the study and were followed for the entire study period. At baseline, 548 people (4%) were co-prescribed opioids and benzodiazepines, 6593 (46%) were prescribed opioids only, 2887 (20%) were prescribed benzodiazepines only, and 4456 (31%) were prescribed neither medication. A total of 3835 (27%) participants were prescribed both medications at least once during the study period. Factors positively associated with concurrent opioid and benzodiazepine prescribing included: depression/mood disorder [adjusted odds ratio (AOR) = 1.32; 95% confidence interval (CI) = 1.22-1.43] and anxiety disorder (AOR = 1.45; 95% CI = 1.27-1.66), whereas female sex (AOR = 0.76; 95% CI = 0.64-0.91) and substance use disorder (SUD) (AOR = 0.82; 95% CI = 0.74-0.90) were negatively associated with the outcome. CONCLUSION: Our findings indicate that co-prescription of opioids and benzodiazepines was seen at some point during study follow-up in over a quarter of PLWH. Given the known risks associated with this prescribing practice, future research can focus on the outcomes of co-prescribing among this patient population and the development of strategies to reduce the co-prescribing of opioids and benzodiazepines.

Impact of Patient-Provider Attachment on Hospital Readmissions Among People Living With HIV: A Population-Based Study.

BACKGROUND: Hospital readmission 30 days after discharge is associated with adverse health outcomes, and people living with HIV (PLWH) experience elevated rates of hospital readmission. Although continuity of care with a health care provider is associated with lower rates of 30-day readmission among the general population, little is known about this relationship among PLWH. The objective of this study is to examine whether engaging with the same provider, defined as patient-provider attachment, is associated with 30-day readmission for this population. SETTING: Data were derived from the Seek and Treat for Optimal Prevention of HIV in British Columbia cohort. METHODS: Using generalized estimating equation with a logit link function, we examined the association between patient-provider attachment and 30-day hospital readmission. We determined whether readmission was due to all cause or to a similar cause as the index admission. RESULTS: Seven thousand thirteen PLWH were hospitalized during the study period. Nine hundred twenty-one (13.1%) were readmitted to hospital for all cause and 564 (8.0%) for the similar cause as the index admission. Patient-provider attachment was negatively associated with 30-day readmission for all causes (adjusted odds ratio = 0.85, confidence interval = 0.83 to 0.86). A second multivariable model indicated that patient-provider attachment was also negatively associated with 30-day readmission for a similar cause (adjusted odds ratio = 0.86, confidence interval = 0.84 to 0.88). CONCLUSIONS: Our results indicate that a higher proportion of patient-provider attachment was negatively associated with 30-day hospital readmission among PLWH. Our study findings support the adoption of interventions that seek to build patient-provider relationships to optimize outcomes for PLWH and enhance health care sustainability.

Incidence of diabetes mellitus and factors associated with its development in HIV-positive patients over the age of 50.

OBJECTIVE: We sought to determine the incidence and factors associated with development of diabetes mellitus (DM) in older HIV-infected individuals. RESEARCH DESIGN AND METHODS: We analyzed data from people living with HIV (PLWH) ≥50 years of age enrolled in a large urban HIV outpatient clinic in Vancouver, British Columbia. Patients were categorized as having DM if they had random blood sugar ≥11.1 mmol/L, fasting blood sugar ≥7 mmol/L, HbA1C ≥6.5%, antidiabetic medication use during the follow-up period, or medical chart review confirming diagnosis of DM. We estimated the probability of developing DM, adjusting for demographic and clinical factors, using a logistic regression model. RESULTS: Among 1065 PLWH followed for a median of 13 years (25th and 75th percentile (Q1-Q3): 9-18), the incidence of DM was 1.61/100 person-years follow-up. In the analysis of factors associated with new-onset DM (n=703), 88% were male, 38% had a history of injection drug use, 43% were hepatitis C coinfected, and median body mass index was 24 kg/m2 (Q1-Q3: 21-27). Median age at antiretroviral therapy (ART) initiation was 48 years (Q1-Q3: 43-53) and at DM diagnosis was 55 years (Q1-Q3: 50-61). Patients who started ART in 1997-1999 and had a longer exposure to older ART were at the highest risk of developing DM. CONCLUSIONS: Among PLWH aged ≥50 years, the incidence of DM was 1.39 times higher than men in the general Canadian population of similar age. ART initiated in the early years of the epidemic and exposure to older ART appeared to be the main drivers of the development of DM.