Increased PrEP uptake and PrEP-RN coincide with decreased HIV diagnoses in men who have sex with men in Ottawa, Canada.

Background: We sought to evaluate if increased uptake of HIV pre-exposure prophylaxis (PrEP) correlated to population-level changes in human immunodeficiency virus (HIV) epidemiology, in a setting with an integrated PrEP delivery system centred on a public health nurse-led PrEP clinic and referral process. Methods: This study was conducted in Ottawa, Canada, where all positive HIV test results are reported to the public health units. Risk factor information is also collected by nurses and subsequently entered into a provincial database. We extracted these data for Ottawa from 2017 to 2021 and restricted our analyses to first-time diagnoses. Results: We identified 154 persons with a new HIV diagnosis. Over this period, the number of new diagnoses among men who have sex with men, the group most targeted for PrEP, decreased by 50%-60%. We did not identify changes in the number of new diagnoses based on race, intravenous drug use or among women. Conclusion: Increasing PrEP uptake in Ottawa in 2017 to 2021 coincided with a significant decrease in new HIV diagnoses among men who have sex with men. PrEP uptake in Ottawa, particularly by those most at risk, is likely supported by an integrated approach via PrEP-RN, a nurse-led public health program where individuals diagnosed with syphilis or rectal gonorrhea or chlamydia receive an automatic offer of PrEP. While these findings cannot causally link PrEP-RN or PrEP with this reduction in new HIV diagnoses, these changes in HIV epidemiology in Ottawa occurred exclusively among the group targeted for PrEP. These data highlight the efficacy and importance of PrEP.

Examining the association between stress and antiretroviral therapy adherence among women living with HIV in Toronto, Ontario.

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

Cohort profile: Development and profile of a population-based, retrospective cohort of diagnosed people living with HIV in Ontario, Canada (Ontario HIV Laboratory Cohort).

PURPOSE: Population-based cohorts of diagnosed people living with HIV (PLWH) are limited worldwide. In Ontario, linked HIV diagnostic and viral load (VL) test databases are centralised and contain laboratory data commonly used to measure engagement in HIV care. We used these linked databases to create a population-based, retrospective cohort of diagnosed PLWH in Ontario, Canada. PARTICIPANTS: A datamart was created by integrating diagnostic and VL databases and linking records at the individual level. These databases contain information on laboratory test results and sociodemographic/clinical information collected on requisition/surveillance forms. Datamart individuals enter our cohort with the first record of a nominal HIV-positive diagnostic test (1985-2015) or VL test (1996-2015), and remain unless administratively lost to follow-up (LTFU; no VL test for >2 years and no VL test in later years). Non-nominal diagnostic tests are excluded as they lack identifying information to permit linkage to other tests. However, individuals diagnosed non-nominally are included in the cohort with record of a VL test. The LTFU rule is applied to indirectly censor for death/out-migration. FINDINGS TO DATE: As of the end of 2015, the datamart contained 40 372 HIV-positive diagnostic tests and 23 851 individuals with ≥1 VL test. Almost half (46.3%) of the diagnostic tests were non-nominal and excluded, although this was lower (~15%) in recent years. Overall, 29 587 individuals have entered the cohort-contributing 229 302 person-years of follow-up since 1996. Between 2000 and 2015, the number of diagnosed PLWH (cohort individuals not LTFU) increased from 8859 to 16 110, and the percent who were aged ≥45 years increased from 29.1% to 62.6%. The percent of diagnosed PLWH who were virally suppressed (<200 copies/mL) increased from 40.7% in 2000 to 79.5% in 2015. FUTURE PLANS: We plan to conduct further analyses of HIV care engagement and link to administrative databases with information on death, migration, physician billing claims and prescriptions. Linkage to other data sources will address cohort limitations and expand research opportunities.

Trends in HIV care cascade engagement among diagnosed people living with HIV in Ontario, Canada: A retrospective, population-based cohort study.

BACKGROUND: The HIV cascade is an important framework for assessing systems of care, but population-based assessment is lacking for most jurisdictions worldwide. We measured cascade indicators over time in a population-based cohort of diagnosed people living with HIV (PLWH) in Ontario, Canada. METHODS: We created a retrospective cohort of diagnosed PLWH using a centralized laboratory database with HIV diagnostic and viral load (VL) test records linked at the individual-level. Individuals enter the cohort with record of a nominal HIV-positive diagnostic test or VL test, and remain unless administratively lost to follow-up (LTFU, >2 consecutive years with no VL test and no VL test in later years). We calculated the annual percent of diagnosed PLWH (cohort individuals not LTFU) between 2000 and 2015 who were in care (≥1 VL test), on ART (as documented on VL test requisition) or virally suppressed (<200 copies/ml). We also calculated time from diagnosis to linkage to care and viral suppression among individuals newly diagnosed with HIV. Analyses were stratified by sex and age. Upper/lower bounds were calculated using alternative indicator definitions. RESULTS: The number of diagnosed PLWH increased from 8,859 (8,859-11,389) in 2000 to 16,110 (16,110-17,423) in 2015. Over this 16-year period, the percent of diagnosed PLWH who were: in care increased from 81% (63-81%) to 87% (81-87%), on ART increased from 55% (34-60%) to 81% (70-82%) and virally suppressed increased from 41% (23-46%) to 80% (67-81%). Between 2000 and 2014, the percent of newly diagnosed individuals who linked to care within three months of diagnosis or achieved viral suppression within six months of diagnosis increased from 67% to 82% and from 22% to 42%, respectively. Estimates were generally lower for females and younger individuals. DISCUSSION: HIV cascade indicators among diagnosed PLWH in Ontario improved between 2000 and 2015, but gaps still remain-particularly for younger individuals.

The impact of drug coverage on viral suppression among people living with HIV in Ontario, Canada.

OBJECTIVES: We investigated the effect of drug coverage on viral suppression (sVL) in Ontario, Canada, where there is no universal coverage of prescription drugs, including antiretroviral therapy (ART). METHODS: Ontarians without employment coverage may be eligible for varying degrees of coverage through government-sponsored programs. Remaining individuals pay all expenses entirely out of pocket. Among participants on ART enrolled in the Ontario HIV Treatment Network Cohort Study (OCS) who were interviewed in 2008-2013 with known or imputable drug coverage, we estimated the prevalence with sVL (< 200 copies/mL) as of their last viral load each year. We calculated prevalence ratios (PR) according to time-updated socio-economic and behavioural factors using multivariable generalized estimating equations with a log-link function. Multiple imputation was used to assess the sensitivity of these findings to different assumed missing data models. RESULTS: One thousand two hundred forty-seven participants were included (3463 person-years). Compared to study participants with employer coverage, individuals covered through the Ontario Drug Benefit (ODB) were less likely to be suppressed (PR, 95% confidence interval (CI) 0.96, 0.93-0.98). After multivariable adjustment, ODB remained independently associated with less success in achieving sVL (adjusted PR, 95% CI 0.98, 0.95-0.99). These findings were robust to different assumptions about the missing data. CONCLUSION: Our findings suggest that drug coverage can affect viral suppression in our setting. Further research is needed to identify the mechanisms by which coverage interacts with individual patient factors to affect viral suppression. Mechanisms to improve access and coverage for ART are needed.

The Use of Multistate Models to Examine Associations of Stress and Adherence With Transitions Among HIV Care States Observed in a Clinical HIV Cohort.

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

Sociodemographic and Health Profile of Heterosexual Men Living With HIV in Ontario, Canada.

In Ontario, Canada, the number of heterosexual men living with HIV has increased over time, yet they remain an understudied population. The study objective was to describe the sociodemographic and clinical characteristics of this population, using data from a multisite clinical cohort of patients receiving HIV care. Sociodemographic and clinical characteristics of men interviewed between 2010 and 2012 were compared according to their self-identified sexual orientation, followed by multivariable linear and logistic regression to assess the association of sexual orientation with CD4 cell count, viral load, hepatitis C co-infection, self-rated health, and mental health concerns after adjustment for covariates. A total of 552 men identified as heterosexual, 2,023 as gay, and 171 as bisexual. Compared to gay and bisexual men, heterosexual men were more likely to have been born outside of Canada (34.8%); more likely to report African, Caribbean, or Black ethnicity (26.4%) or Indigenous ethnicity (13.6%); and more likely to have low socioeconomic status (59.5% earning less than $20,000 per year), and/or a history of injection drug use (31.7%). Relative to gay men, heterosexual men had 5.19 times the odds of co-infection with hepatitis C virus regardless of injection drug use history (95% confidence interval = 3.87-6.96), and 40% lower odds of rating their health as excellent or good (95% confidence interval = 0.50-0.84). HIV-positive heterosexual men in Ontario constituted a socially marginalized group characterized by a high prevalence of injection drug use history and hepatitis C co-infection.

Social determinants of health and retention in HIV care in a clinical cohort in Ontario, Canada.

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

Individual variability in response to a single sickling event for normal, sickle cell, and sickle trait erythrocytes.

Hemoglobin S (Hb-S) polymerization is the primary event in sickle cell disease causing irreversible damage to red blood cell (RBC) membranes over repeated polymerization cycles. A single polymerization triggered by a hypoxic environment was reported to result in reversibly (upon reoxygenation) decreased RBC deformability and increased mechanical fragility (MF). Individualized responses have not been reported, although RBC fragility can vary significantly even among healthy individuals. This study evaluates individual variability in response to a single hypoxia-induced sickling event, through changes in RBC MF. Blood was drawn from 10 normal (AA), 11 sickle cell (SS), and 7 sickle trait (AS) subjects-with Hb-S fraction, osmotic fragility, and medical history also collected. Mechanical stress was applied using a bead mill at 50-Hz oscillation for 0.5-30 minutes. MF profiles here give percent hemolysis upon successive durations of stressing. MF was measured for AA, SS, and AS cells-each equilibrated (1) with air, (2) with nitrogen in an anaerobic chamber, and (3) with air after the hypoxic event. While AA subjects exhibited significantly different changes in fragility upon hypoxia, in all cases there was recovery to close to the initial MF values on reoxygenation. For AS subjects, recovery at reoxygenation was observed only in about half of the cases. Fragility of SS cells increased in hypoxia and decreased with reoxygenation, with significantly variable magnitude of recovery. The variability of response for individual AS and SS subjects indicates that some are potentially at higher risk of irreversible hypoxia-induced membrane damage.

Sexual behaviors among women living with HIV in Ontario, Canada.

Understanding the sexual activities and partnerships of women living with human immunodeficiency virus (HIV) remains important to promote healthy sexuality and to reduce the transmission of HIV and other sexually transmitted infections. We described sexual behaviors of women living with HIV enrolled in an ongoing study in Ontario, Canada. Data were available from 582 women who self-completed a sexual behavior questionnaire between 2010 and 2012. Nearly half (46.1%) of women reported a sexual partner in the preceding three months; women less likely to be sexually active were older, Black/African, separated, divorced, widowed, single, and unemployed. Most sexually active women had one partner (76.4%), a regular partner (75.9%), male (96.2%) partner(s), and partners who were HIV-negative or unknown HIV status (75.2%). Women were more likely to use a condom with HIV-negative/status unknown partners (81.3%) than with HIV-positive partners (58.6%; p = .008). Only 8.0% of sexually active women reported condomless sex with a discordant HIV-negative/status unknown partner when their viral load was detectable. Overall, most women living with HIV were sexually inactive or engaged in sexual activities that were low risk for HIV transmission.

Promoting HIV Testing for Gay and Bisexual Men: An Evaluation of the 2011-2012 Campaign in Toronto and Ottawa.

This article reports on a social marketing campaign directed toward high-risk men who have sex with men in Toronto and Ottawa to encourage testing for HIV and syphilis; improve knowledge about HIV transmission, seroconversion symptoms, and the HIV window period; and heighten awareness of syphilis transmission and its relationship to facilitating HIV transmission. Evaluation data were collected from a large-scale online pre-and postcampaign survey of sexually active men who have sex with men and from laboratory testing data. Men who turned up to be tested also filled out an exit survey. The campaign websites attracted some 15,000 unique visitors, 54% of whom had an IP address in Toronto or Ottawa. Laboratory data showed a 20% increase in HIV testing in Toronto over the campaign compared to the previous year. The overall rate of HIV-positive tests remained relatively constant. Knowledge levels about seroconversion symptoms, sexually transmitted infection and HIV transmission, and the HIV window period were significantly better among postcampaign survey respondents aware of the campaign compared to postcampaign respondents who were not aware and compared to precampaign respondents.

Design and implementation of a sexual health intervention for migrant construction workers situated in Shanghai, China.

BACKGROUND: China's growing population of internal migrants has exceeded 236 million. Driven by rapid development and urbanization, this extreme population mobility creates opportunities for transmission of HIV and sexually-transmitted infections (STI). Large numbers of rural migrants flock to megacities such as Shanghai in search of employment. Although migrants constitute a key population at heightened risk of acquiring HIV or an STI, there is a lack of easily accessible sexual health services available for them. In response, we designed a short, inexpensive sexual health intervention that sought to improve HIV and STI knowledge, while reducing stigma, risky sexual behaviour, and sexual transmission of HIV and STI among migrant construction workers (MCW) situated in Shanghai, China. RESULTS: We implemented a three-armed, community-randomized trial spread across three administrative districts of Shanghai. The low-intensity intervention included educational pamphlets. The medium-intensity intervention included pamphlets, posters, and videos. The high-intensity intervention added group and individual counselling sessions. Across 18 construction sites, 1871 MCW were allocated at baseline to receive one intervention condition. Among baseline participants, 1304 workers were retained at 3-months, and 1013 workers were retained at 6-months, representing a total of 579 person-years of follow-up. All workers, regardless of participation, had access to informational materials even if they did not participate in the evaluation. Overall outputs included: 2284 pamphlets distributed, 720 posters displayed, 672 h of video shown, 376 participants accessed group counselling, and 61 participants attended individual counselling sessions. A multivariable analysis of participation found that men (aOR = 2.2; 95 % CI 1.1, 4.1; p = 0.036), workers situated in Huangpu district (aOR = 5.0; 95 % CI 2.6, 9.5; p < 0.001), and those with a middle school education (aOR = 1.9; 95 % CI 1.2, 3.0; p = 0.01) were more likely to have participated in intervention activities. CONCLUSION: A brief educational intervention that prioritized ease of delivery to a highly mobile workforce was feasible and easily accessed by participants. Routine implementation of sexual health interventions in workplaces that employ migrant labour have the potential to make important contributions toward improving HIV and STI outcomes among migrant workers in China's largest cities.

Implementation and Operational Research: Engagement in HIV Care Among Persons Enrolled in a Clinical HIV Cohort in Ontario, Canada, 2001-2011.

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

Similar donors-similar blood?

BACKGROUND: Red blood cell (RBC) storage lesions have been suggested as contributing factors to suboptimal clinical outcomes. While undesirable effects of storage are well documented, their clinical relevance is still debated. Focus on storage time as the sole determinant of RBC quality ignores the variability in cell properties that may depend on factors other than age. Mechanical fragility (MF) aggregately reflects many storage-related functional and structural changes. This study evaluates interdonor versus intradonor variability, throughout storage, of both MF and autohemolysis (AH). STUDY DESIGN AND METHODS: Thirteen uniformly manufactured RBC units were collected initially as whole blood from nonsmoking, group A+, male Caucasian research donors. Mechanical stress was applied using a bead mill with oscillation at 50 Hz over durations varying from 0.5 to 60 minutes. MF profiles were described in terms of percent hemolysis after stresses of specified durations. Two months later, 11 of the 13 donors returned and assays were performed using the same protocol to allow comparison of intradonor versus interdonor variation. RESULTS: At 5 days postcollection, RBC MF profiles exhibited marked interdonor variability (up to twofold) overall. Both autolysis and MF across all units increased during storage-with rates of these increases varying by up to 10-fold for certain MF variables. Especially high AH and MF were observed for an outlier donor (with p < 0.05), for whom follow-up revealed previously undisclosed hereditary hypertriglyceridemia (levels exceeding approx. 1000 mg/dL). CONCLUSIONS: RBCs, even from similar donors, vary significantly in levels and changes of both AH and MF, the clinical significance of which must still be ascertained. While further study is needed, donors with severe hypertriglyceridemia may not be appropriate as blood donors due to the unacceptable level of hemolysis observed during storage of our affected study subject.

Demographic and clinical factors correlating with high levels of psychological distress in HIV-positive women living in Ontario, Canada.

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