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.

Access to care and impact on HIV treatment interruptions during the COVID-19 pandemic among people living with HIV in British Columbia.

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

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.

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.

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).

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.

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.

Progress towards World Health Organization HIV Infection 95-95-95 measures in Newfoundland and Labrador, Canada.

The HIV program in Newfoundland and Labrador (NL) provides care for all persons living with HIV (PLWH) in NL, yet progress toward UNAIDS 95-95-95 goals for diagnosis, linkage to care and viral suppression has not previously been documented. This analysis describes engagement in HIV care and virologic outcomes for the NL cohort in 2016 and 2019 and compares this data to the Canadian HIV Observational Cohort (CANOC). A retrospective review of the NL clinic included adults aged >18 years and descriptive statistics for demographics, risk factors, and clinical variables were assessed and compared using χ2 test or Fisher's Exact test (categorical) or Wilcoxon Sum Rank test (continuous). Engagement in care and virologic outcomes for the NL cohort were consistently high over the 2016 to 2019 period with > 98% on antiretroviral therapy (ART), and > 96% having a suppressed virus load. Engagement in care and virologic outcomes among PLWH in NL is high and compares favorably to a national cohort.

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.

Trends in Use of Combination Antiretroviral Therapy and Treatment Response from 2000 to 2016 in the Canadian Observational Cohort (CANOC): A Longitudinal Cohort Study.

Background: Advances in treatment have turned HIV from a terminal illness to a more manageable condition. Over the past 20 years, there have been considerable changes to HIV treatment guidelines, including changes in preferred antiretrovirals and timing of initiation of combination antiretroviral therapy (cART). Objective: To examine real-world trends in cART utilization, viral control, and immune reconstitution among people living with HIV in Canada. Methods: Data were obtained from the Canadian Observational Cohort (CANOC). CANOC participants were eligible if they were antiretroviral therapy-naive at entry and initiated 3 or more antiretrovirals on or after January 1, 2000; if they were at least 18 years of age at treatment initiation; if they were residing in Canada; and if they had at least 1 viral load determination and CD4 count within 1 year of CANOC entry. Baseline and annual mean CD4 counts were categorized as less than 200, 200-350, 351-500, and more than 500 cells/mm3. Annual mean viral loads were reported as suppressed (< 50 copies/mL), low (50-199 copies/mL), or high detectable (≥ 200 copies/mL). The cART regimens were reported yearly. Results: All CANOC participants were included (n = 13 040). Over the study period, the proportion of individuals with an annual mean CD4 count above 500 cells/mm3 increased from 16.3% to 65.8%, while the proportion of individuals with an undetectable mean viral load increased from 10.6% to 83.2%. As of 2007, the most commonly prescribed 2-agent nucleoside reverse transcriptase inhibitor backbone was tenofovir disoproxil fumarate and emtricitabine. In terms of third agents, non-nucleoside reverse transcriptase inhibitors were the most common class in the periods 2000-2003 and 2014-2015, protease inhibitors were most common in the period 2004-2013, and integrase inhibitors were most common in 2016. Conclusions: Concordance with treatment guidelines was demonstrated over time with respect to cART prescribing and immunologic and virologic response.

Contexte: Les progrès effectués dans le domaine des traitements ont transformé le VIH. Celui-ci est passé d'une maladie en phase terminale à une maladie plus gérable. Au cours des 20 dernières années, des changements considérables ont eu lieu dans les directives de traitement du VIH, y compris des changements dans les antirétroviraux privilégiés et le moment de l'initiation de la thérapie antirétrovirale combinée (TARc). Objectif: Examiner les tendances réelles de l'utilisation de la TARc, du contrôle viral et de la reconstitution immunitaire chez les personnes vivant avec le VIH au Canada. Méthodes: Les données ont été obtenues auprès de la Canadian Observational Cohort (CANOC). Les participants à la CANOC étaient admissibles s'ils n'avaient jamais reçu de traitement antirétroviral à l'entrée et avaient commencé la prise de 3 antirétroviraux ou plus le 1er janvier 2000 ou après cette date; s'ils avaient au moins 18 ans au moment du début du traitement; s'ils résidaient au Canada; et s'ils avaient au moins 1 charge virale et un nombre de CD4 dans l'année suivant l'entrée à la CANOC. Les numérations initiales et annuelles moyennes de CD4 ont été classées comme inférieures à 200, 200 à 350, 351 à 500, et supérieures à 500 cellules/mm3. Les charges virales moyennes annuelles ont été signalées comme supprimées (< 50 copies/mL), faibles (50 à 199 copies/mL) ou élevées détectables (≥ 200 copies/mL). Les régimes de la TARc ont été rapportés chaque année. Résultats: Tous les participants à la CANOC ont été inclus (n = 13040). Au cours de la période d'étude, la proportion de personnes ayant une numération CD4 moyenne annuelle supérieure à 500 cellules/mm3 est passée de 16,3 % à 65,8 %, tandis que la part de personnes ayant une charge virale moyenne indétectable est passée de 10,6 % à 83,2 %. En 2007, la bithérapie de base d'inhibiteurs nucléosidiques de la transcriptase inverse la plus couramment prescrite était le fumarate de ténofovir disoproxil et l'emtricitabine. En matière de troisièmes agents, la classe la plus courante dans les périodes 2000­2003 et 2014­2015 était les inhibiteurs non nucléosidiques de la transcriptase inverse; les plus courants dans la période 2004­2013 étaient les inhibiteurs de protéase; et les inhibiteurs de l'intégrase étaient les plus courants en 2016. Conclusions: La concordance avec les directives de traitement a été démontrée au fil du temps en ce qui concerne la prescription de la cART et la réponse immunologique et virologique.

A 20-year population-based study of all-cause and cause-specific mortality among people with concurrent HIV and psychotic disorders.

OBJECTIVE: We aimed to characterize mortality among people with HIV (PWH) and psychotic disorders (PWH/psychosis+) vs. PWH alone (PWH/psychosis-). METHOD: A population-based analysis of mortality in PWH (age ≥19) in British Columbia (BC) from April 1996 to March 2017 was conducted using data from the Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) study. Deaths were identified from the Vital Statistics Data (classified as HIV vs. non-HIV causes). Mortality trends across all fiscal years were examined. Cox models assessed the hazard of psychotic disorders on mortality; possible differences between schizophrenia and nonschizophrenia types of psychotic disorders were also evaluated. RESULTS: Among 13 410 PWH included in the analysis, 1572 (11.7%) met the case definition for at least one psychotic disorder. Over the study period, 3274 deaths (PWH/psychosis-: n  = 2785, PWH/psychosis+: n  = 489) occurred. A decline over time in all-cause mortality and HIV-related mortality was observed in both PWH/psychosis+ and PWH/psychosis- ( P value <0.0001). A decline in non-HIV mortality was observed among PWH/psychosis- ( P value = 0.003), but not PWH/psychosis+ ( P value = 0.3). Nonschizophrenia psychotic disorders were associated with increased risk of mortality; adjusted hazard ratios with (95% confidence intervals): all-cause 1.75 (1.46-2.09), HIV-related 2.08 (1.60-2.69), non-HIV-related 1.45 (1.11-1.90). Similar associations between schizophrenia and mortality were not observed. CONCLUSION: People with co-occurring HIV and nonschizophrenia psychotic disorders experienced a significantly higher risk of mortality vs. PWH without any psychotic disorder. Implementing care according to syndemic models considering interactions between HIV and particularly episodic psychotic disorders could help manage mortality risk more effectively among PWH/psychosis+.

Knowledge of hepatitis C and awareness of reinfection risk among people who successfully completed direct acting antiviral therapy.

BACKGROUND: Hepatitis C virus (HCV) education may be changing following the simplification of HCV treatment and emergence of direct acting antiviral (DAA). We aimed to characterize HCV knowledge among people who recently completed DAA therapy. METHODS: The Per-SVR (Preservation of Sustained Virologic Response) is a prospective cohort of patients who achieved a sustained virologic response upon successful completion of DAA therapy. The per-SVR study provided the sampling frame of participants who completed a psychometrically validated 19-item HCV knowledge scale at cohort entry (n = 227). To score the questionnaire, for each correct response one point was awarded, with no point for incorrect response. We assessed mean HCV knowledge score in the overall sample and mutually exclusive populations: people who inject drug (PWID) (n = 71); people with co-occurring HIV (n = 23); PWID and co-occurring HIV (n = 29), and others (n = 104) Using a latent class analysis based on distal outcome, we identified unobserved subgroups and assessed HCV knowledge amongst them. RESULTS: Total mean (SD) percent of correct responses were 83 (11) in the overall sample; 83 (10) in PWID; 79 (12) in people with co-occurring HIV; 81 (10) in PWID and co-occurring HIV, and 84 (11) in rest of the sample Three latent groups were identified: baby boomers who ever experienced homelessness (n = 126); women sex workers who ever experienced homelessness (n = 68); men who inject drug, ever experienced homelessness and had ever diagnosis of mental health disorders (n = 18). Mean percent of correct responses were 85 (8), 82 (11), 85 (10), in latent class 1, 2, and 3, respectively. CONCLUSION: Patients successfully treated with DAAs had a high HCV knowledge. High knowledge and awareness of reinfection among complex patient groups often facing barriers to HCV care is encouraging and emphasizes the positive outcomes of universal access to treatment.

Impact of Canadian human immunodeficiency virus non-disclosure case law on experiences of violence from sexual partners among women living with human immunodeficiency virus in Canada: Implications for sexual rights.

OBJECTIVES: People living with human immunodeficiency virus in Canada can face criminal charges for human immunodeficiency virus non-disclosure before sex, unless a condom is used and their viral load is <1500 copies/mL. We measured the reported impact of human immunodeficiency virus non-disclosure case law on violence from sexual partners among women living with human immunodeficiency virus in Canada. METHODS: We used cross-sectional survey data from wave 3 participant visits (2017-2018) within Canadian HIV Women's Sexual and Reproductive Health Cohort Study; a longitudinal, community-based cohort of women living with human immunodeficiency virus in British Columbia, Ontario and Quebec. Our primary outcome was derived from response to the statement: '[HIV non-disclosure case law has] increased my experiences of verbal/physical/sexual violence from sexual partners'. Participants responding 'strongly agree/agree' were deemed to have experienced increased violence due to the law. Participants responding 'not applicable' (i.e. those without sexual partners) were excluded. Multivariate logistic regression identified factors independently associated with increased violence from sexual partners due to human immunodeficiency virus non-disclosure case law. RESULTS: We included 619/937 wave 3 participants. Median age was 46 (interquartile range: 39-53) and 86% had experienced verbal/physical/sexual violence in adulthood. Due to concerns about human immunodeficiency virus non-disclosure case law, 37% had chosen not to have sex with a new partner, and 20% had disclosed their human immunodeficiency virus status to sexual partners before a witness. A total of 21% self-reported that human immunodeficiency virus non-disclosure case law had increased their experiences of verbal/physical/sexual violence from sexual partners. In adjusted analyses, women reporting non-White ethnicity (Indigenous; African/Caribbean/Black; Other), unstable housing and high human immunodeficiency virus-related stigma had significantly higher odds of reporting increased violence from sexual partners due to human immunodeficiency virus non-disclosure case law. CONCLUSION: Findings bolster concerns that human immunodeficiency virus criminalization is a structural driver of intimate partner violence, compromising sexual rights of women living with human immunodeficiency virus. Human immunodeficiency virus non-disclosure case law intersects with other oppressions to regulate women's sexual lives.

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.

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.

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.

An exact arithmetic toolbox for a consistent and reproducible structural analysis of metabolic network models.

Constraint-based models are currently the only methodology that allows the study of metabolism at the whole-genome scale. Flux balance analysis is commonly used to analyse constraint-based models. Curiously, the results of this analysis vary with the software being run, a situation that we show can be remedied by using exact rather than floating-point arithmetic. Here we introduce MONGOOSE, a toolbox for analysing the structure of constraint-based metabolic models in exact arithmetic. We apply MONGOOSE to the analysis of 98 existing metabolic network models and find that the biomass reaction is surprisingly blocked (unable to sustain non-zero flux) in nearly half of them. We propose a principled approach for unblocking these reactions and extend it to the problems of identifying essential and synthetic lethal reactions and minimal media. Our structural insights enable a systematic study of constraint-based metabolic models, yielding a deeper understanding of their possibilities and limitations.

Multicoil2: predicting coiled coils and their oligomerization states from sequence in the twilight zone.

The alpha-helical coiled coil can adopt a variety of topologies, among the most common of which are parallel and antiparallel dimers and trimers. We present Multicoil2, an algorithm that predicts both the location and oligomerization state (two versus three helices) of coiled coils in protein sequences. Multicoil2 combines the pairwise correlations of the previous Multicoil method with the flexibility of Hidden Markov Models (HMMs) in a Markov Random Field (MRF). The resulting algorithm integrates sequence features, including pairwise interactions, through multinomial logistic regression to devise an optimized scoring function for distinguishing dimer, trimer and non-coiled-coil oligomerization states; this scoring function is used to produce Markov Random Field potentials that incorporate pairwise correlations localized in sequence. Multicoil2 significantly improves both coiled-coil detection and dimer versus trimer state prediction over the original Multicoil algorithm retrained on a newly-constructed database of coiled-coil sequences. The new database, comprised of 2,105 sequences containing 124,088 residues, includes reliable structural annotations based on experimental data in the literature. Notably, the enhanced performance of Multicoil2 is evident when tested in stringent leave-family-out cross-validation on the new database, reflecting expected performance on challenging new prediction targets that have minimal sequence similarity to known coiled-coil families. The Multicoil2 program and training database are available for download from http://multicoil2.csail.mit.edu.