HIV Treatment Network Cohort Study Research Articles

Hepatitis C virus testing in a clinical HIV cohort in Ontario, Canada, 2000 to 2015.

BackgroundHIV‐positive individuals may acquire HCV via injection drug use (IDU) and condomless anal sex. HIV care provides opportunities for HCV testing and cure with direct‐acting antiviral agents (DAAs).MethodsWe analyzed data from the Ontario HIV Treatment Network Cohort Study. Among those not HCV‐positive or diagnosed previously (n = 4586), we used Cox regression to test the rates of ever HCV testing (serological or RNA) in HIV care by DAA era (pre‐DAA: 2000‐2010; after DAA: 2011‐2015) and compared the proportion diagnosed with HCV. We identified correlates of annual proportions of serological testing using Poisson generalized estimating equations.ResultsAfter DAA vs pre‐DAA, the hazard rate ratio (95% CI) of ever HCV testing was 1.70 (1.59, 1.81). The proportion (95% CI) tested annually increased from 9.2% (8.0%, 10.7%) in 2000 to 39.1% (37.1%, 41.1%) in 2015 (P < 0.0001). The proportion diagnosed with HCV declined by 74% pre‐DAA to 11% after DAAs. Annual testing increased per calendar year (16% steeper slope after DAA vs pre‐DAA) and was more common among men who have sex with men; those more educated (post‐secondary vs ≤ high school); and those positive for syphilis or reporting any IDU. Annual testing decreased per decade of age and time since HIV diagnosis.DiscussionAnnual HCV testing increased over time with higher testing among those reporting sexual or IDU risk factors, but fell short of clinical guidelines. Targeted interventions to boost testing may be needed to close these gaps and reach WHO 2030 HCV elimination targets.

Racial Disparities in Anal Cancer Screening Among Men Living With HIV: Findings From a Clinical Cohort Study.

Our objective was to quantify the extent of anal cancer screening among men receiving HIV specialty care in Ontario, Canada, and evaluate factors associated with screening. Cross-sectional questionnaire within a multisite clinical HIV cohort. A questionnaire assessing knowledge and experience with human papillomavirus-associated diseases and their prevention was administered in 2016-2017 to 1677 men in the Ontario HIV Treatment Network Cohort Study. We used logistic regression to identify factors associated with having discussed screening with a health care provider and self-reported receipt of screening [digital anal rectal examinations (DARE); anal cytology or anoscopy]. Results reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Forty percent of men reported ever having had anal cytology/anoscopy, and 70% had ever had DARE. After accounting for differences in age, sexual orientation, years since HIV diagnosis, previous diagnosis with AIDS, knowing someone with human papillomavirus-associated cancer, comfort discussing anal health, education, and income, the proportion screened differed by self-identified race. Compared with white men, Asian men were less likely to have discussed screening with a health care provider (aOR = 0.48; 95% CI: 0.29 to 0.80) or to have been screened by DARE (aOR = 0.27; 95% CI: 0.17 to 0.44) or anal cytology/anoscopy (aOR = 0.51; 95% CI: 0.31 to 0.83), and African, Caribbean, or black men (aOR = 0.47; 95% CI: 0.31 to 0.70) were less likely to have had DARE. Results were consistent when restricting the analyses to gay, bisexual, and other men who have sex with men. Our findings highlight the potential for disparities in anal cancer screening that need to be considered when developing guidelines and screening programs to reduce the burden of anal cancer among men living with HIV and ensure health equity.

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.

Late diagnosis, delayed presentation and late presentation among persons enrolled in a clinical HIV cohort in Ontario, Canada (1999-2013).

Timely HIV diagnosis and presentation to medical care are important for treatment and prevention. Our objective was to measure late diagnosis, delayed presentation and late presentation among individuals in the Ontario HIV Treatment Network Cohort Study (OCS) who were newly diagnosed in Ontario. The OCS is a multi-site clinical cohort study of people living with HIV in Ontario, Canada. We measured prevalence of late diagnosis [CD4 count <350 cells/μL or an AIDS-defining condition (ADC) within 3months of HIV diagnosis], delayed presentation (≥3months from HIV diagnosis to presentation to care), and late presentation (CD4 count <350 cells/μL or ADC within 3months of presentation). We identified characteristics associated with these outcomes and explored their overlap. A total of 1819 OCS participants were newly diagnosed in Ontario from 1999 to 2013. Late diagnosis (53.0%) and presentation (54.0%) were common, and a quarter (23.1%) of participants were delayed presenters. In multivariable models, the participants of delayed presentation decreased over calendar time, but that of late diagnosis/presentation did not. Late diagnosis contributed to the majority (> 87%) of late presentation, and the prevalence of delayed presentation was similar among those diagnosed late versus early (13.4 versus 13.4%, respectively; P=0.99). Characteristics associated with higher odds of late diagnosis/presentation in multivariable analyses included older age at diagnosis/presentation; African, Caribbean and Black race/ethnicity; Indigenous race/ethnicity; female sex; and being a male who did not report sex with men. There were lower odds of late diagnosis/presentation among participants who had ever injected drugs. In contrast, delayed presentation risk factors included younger age at diagnosis and having ever injected drugs. Late presentation is common in Ontario, as it is in other high-income countries. Our findings suggest that efforts to reduce late presentation should focus on facilitating earlier diagnosis for the populations identified in this analysis.

A longitudinal investigation of the association between cannabis use and alcohol use among people living with HIV

BackgroundBoth cannabis use and alcohol use are elevated among people living with HIV, but few studies have investigated the relationship between cannabis use and alcohol use in this population. This study examined the longitudinal association between cannabis use and alcohol use among people living with HIV and explored the moderating role of medicinal vs. recreational cannabis use. MethodParticipants were cannabis users (N=763) enrolled in the Ontario HIV Treatment Network Cohort Study (67% White, 88% male, 68% gay, median income in the $40,000-$50,000 range). Participants completed assessments of cannabis use, reasons for cannabis use, and alcohol use at baseline and at annual follow-ups (M = 3.42 completed assessments). Multilevel modeling was used to examine between-person and within-person associations between cannabis use and alcohol use over time. ResultsGreater average frequency of cannabis use was associated with greater average alcohol consumption across participants. Participants classified as medicinal cannabis users reported more frequent cannabis use and less alcohol use on average than recreational cannabis users. Further, within-person changes in cannabis use over time were positively associated with corresponding changes in alcohol use for recreational cannabis users but not for medicinal users. ConclusionCannabis use and alcohol use were positively associated over time among people living with HIV, although this association was specific to those using cannabis for recreational reasons. As alcohol use in this population poses significant health risks, more research on the link between cannabis use and alcohol use is needed, particularly in light of recent changes to cannabis regulations.

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

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). 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. 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. 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 Effect of MSM and CD4+ Count on the Development of Cancer AIDS (AIDS-defining Cancer) and Non-cancer AIDS in the HAART Era.

Background: The HIV epidemic is increasing among Men who have Sex with Men (MSM) and the risk for AIDS defining cancer (ADC) is higher among them.Objective: To examine the effect of MSM and CD4+ count on time to cancer AIDS (ADC) and non-cancer AIDS in competing risks setting in the HAART era.Method: Using Ontario HIV Treatment Network Cohort Study data, HIV-positive adults diagnosed between January 1997 and October 2012 having baseline CD4+ counts ≤ 500 cells/mm3 were evalu-ated. Two survival outcomes, cancer AIDS and non-cancer AIDS, were treated as competing risks. Kaplan-Meier analysis, Cox cause-specific hazards (CSH) model and joint modeling of longitudinal and survival outcomes were used.Results: Among the 822 participants, 657 (79.9%) were males; 686 (83.5%) received anti-retroviral (ARV) ever. Regarding risk category, the majority (58.5%) were men who have Sex with men (MSM). Mean age was 37.4 years (SD = 10.3). In the multivariate Cox CSH models, MSM were not associated with cancer AIDS but with non-cancer AIDS [HR = 2.92; P = 0.055, HR = 0.54; P = 0.0009, respectively]. However, in joint models of longitudinal and survival outcomes, MSM were associated with cancer AIDS but not with non-cancer AIDS [HR = 3.86; P = 0.013, HR = 0.73; P = 0.10]. CD4+ count, age, ARV ever were associated with both events in the joint models.Conclusion: This study demonstrates the importance of considering competing risks, and time-dependent biomarker in the survival model. MSM have higher hazard for cancer AIDS. CD4+ count is associated with both survival outcomes.

Childhood Adversities and Physical and Mental Health Outcomes in Adults Living with HIV: Findings from the Ontario HIV Treatment Network Cohort Study.

We sought to estimate the prevalence of childhood adversity and examine its relationship with health outcomes among people living with HIV. Study participants included 1409 adults living with HIV and receiving care in Toronto, Canada. Data on childhood adversity, health behaviors, HIV outcome measures, depression, and health-related quality of life (HRQOL) were collected through face-to-face interviews and medical records. Statistical analyses included multivariable linear and logistic regression modeling. The prevalence of any childhood adversity was 71% (individual types ranged from 11% to 44%) and higher prevalence was associated with younger age, Indigenous or African/Caribbean/Black ethnicity, lower socioeconomic status, and higher rates of cigarette smoking and nonmedicinal drug use. Greater number of childhood adversities was associated with greater odds of depression and decreasing mental HRQOL. HIV care providers need to screen for childhood adversities and address childhood trauma within the context of HIV care.

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

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. 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. 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. 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.

High retention in HIV care at a tertiary care centre in Toronto, Canada

ABSTRACTPoor retention in HIV care is associated with poor clinical outcomes and mortality. Previous studies of predictors of poor retention have been conducted with a wide variety of populations, using different measures of retention, and occasionally have conflicting results. We studied demographic and psychosocial factors associated with inter-visit interval length in a setting of universal health care and modern cART. Patients attending ≥2 appointments with an HIV specialist at the Toronto General Hospital Immunodeficiency Clinic from 2004 to 2013 were studied. A sub-analysis included psychosocial measures from annual questionnaires for Ontario HIV Treatment Network Cohort Study (OCS) participants. Median inter-visit interval and constancy (percentage of 4-month intervals with ≥1 visit) were calculated by patient. Multivariable generalized estimating equation models identified factors associated with inter-visit interval length and intervals ≥12 months. 1591 patients were included. 615 patients completed an OCS questionnaire and were more likely to be older white MSM from Canada with a viral load (VL) <50 copies/ml. The median (IQR) of patients’ median inter-visit intervals was 3.15 (2.78, 3.84) months and median (IQR) constancy was 90% (71%, 100%). Two percent of inter-visit intervals were ≥12 months and 25% of patients had ≥1 interval ≥12 months. Longer inter-visit intervals were associated with younger age, white race, earlier calendar year, longer duration of HIV, VL < 50 copies/mL and higher CD4 counts. Patients who were younger, white, had injection drug use as a risk factor, had a longer duration of HIV, and had VL ≥50 copies/mL were more likely to have an inter-visit interval ≥12 months. In the OCS sub-analysis including psychosocial variables, lower levels of depression were associated with longer inter-visit intervals. Retention at this tertiary care centre was high. Efforts to maximize attendance should focus on younger patients and those with substance abuse issues.

Trends and Correlates of Cigarette Smoking and Its Impacts on Health-Related Quality of Life Among People Living with HIV: Findings from the Ontario HIV Treatment Network Cohort Study, 2008-2014.

We sought to examine the trends of cigarette smoking, identify correlates of smoking, and examine the impacts of smoking on health-related quality of life (HRQOL) among people living with HIV in Ontario, Canada. Study sample included 4473 individuals receiving care and enrolled in the Ontario HIV Treatment Network Cohort Study. Self-report data on cigarette smoking, HRQOL, and demographic and sociobehavioral variables were collected between 2008 and 2014 through annual face-to-face interviews. Clinical data were abstracted from participants' medical records and enhanced through linkage with a provincial public health laboratory database. Analyses included descriptive statistics, generalized logit regression, and linear mixed-effects modeling. At first interview, 1760 participants (39.3%) were current cigarette smokers. Smoking prevalence declined annually by 1.6% between 2008 and 2014, but remained much higher than the prevalence in the general population. Current cigarette smokers were more likely to be younger, male, white or indigenous, Canadian-born, single, unemployed with lower education, heavy drinkers, nonmedicinal drug users, and to have current depression than former cigarette smokers or those who never smoked. Current cigarette smokers also had significantly (p < 0.001) worse SF-12 physical component summary (β = -2.07) and SF-12 mental component summary (β = -1.08) scores than those who never smoked after adjusting for demographic, socioeconomic, and HIV-related clinical variables. To reduce the burden of cigarette smoking, cessation interventions that take into account the complex social, economic, and medical needs of people living with HIV are needed urgently.

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

ABSTRACTContinuous 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

Prevalence, Recurrence, and Incidence of Current Depressive Symptoms among People Living with HIV in Ontario, Canada: Results from the Ontario HIV Treatment Network Cohort Study.

IntroductionCurrent studies of depression among people living with HIV focus on describing its point prevalence. Given the fluctuating nature of depression and its profound impacts on clinical and quality-of-life outcomes, this study aimed to examine the prevalence, recurrence and incidence of current depressive symptoms and its underlying catalysts longitudinally and systematically among these individuals.MethodsWe conducted a prospective cohort study between October 1, 2007 and December 31, 2012 using longitudinal linked data sources. Current depressive symptoms was identified using the Centre for Epidemiologic Studies Depression Scale or the Kessler Psychological Distress Scale, first at baseline and again during follow-up interviews. Multivariable regressions were used to characterize the three outcomes.ResultsOf the 3,816 HIV-positive participants, the point prevalence of depressive symptoms was estimated at 28%. Of the 957 participants who were identified with depressive symptoms at baseline and who had at least two years of follow-up, 43% had a recurrent episode. The cumulative incidence among 1,745 previously depressive symptoms free participants (at or prior to baseline) was 14%. During the five-year follow-up, our multivariable models showed that participants with greater risk of recurrent cases were more likely to feel worried about their housing situation. Participants at risk of developing incident cases were also likely to be younger, gay or bisexual, and unable to afford housing-related expenses.ConclusionsDepressive symptoms are prevalent and likely to recur among people living with HIV. Our results support the direction of Ontario’s HIV/AIDS Strategy to 2026, which addresses medical concerns associated with HIV (such as depression) and the social drivers of health in order to enhance the overall well-being of people living with or at risk of HIV. Our findings reinforce the importance of providing effective mental health care and demonstrate the need for long-term support and routine management of depression, particularly for individuals at high risk.

Burden and risk factors for gastrointestinal symptom distress in HIV patients in the modern antiretroviral era

ABSTRACTIn the modern antiretroviral (ARV) era, there is limited knowledge about the prevalence and risk factors for HIV patient-reported gastrointestinal (GI) symptoms (diarrhoea/soft stool, nausea/vomiting, bloating/painful abdomen, loss of appetite, and weight loss/wasting) and distress. We prospectively analysed data (2007–2014) on distressing GI symptoms from the Ontario HIV Treatment Network Cohort Study, which follows people attending HIV clinics. Using generalized estimating equations with a logit link, we estimated the associations of psychosocial, demographic, behavioural, and clinical factors with each GI symptoms compared to asymptomatic and non-bothersome symptoms. Among 1532 included participants, 80.4% were male, mean age was 45 years, and 64.6% reported being men who have sex with men. Most were Caucasian (56.3%), a median time since HIV diagnosis of 9.8 years (interquartile range (IQR): 4.1–16.9), and 83.1% were on ARV. More than two-thirds (68.7% (95% confidence intervals (CI): 63.1% to 69.2%)) reported one or more symptoms with a median of 1.2 (IQR: 0–1.7). The proportion remained stable over time since HIV diagnosis and ARV initiation. Risk factors varied for multivariable models. A strong association with Centre for Epidemiologic Studies Depression scale scores of ≥23 was found for all symptoms. Adjusted odds ratios (95% CI) were 1.72 (1.39–2.12), 2.95 (2.33–3.72), 2.20 (1.81–2.68), 4.97 (3.99–6.19), and 2.98 (2.52–3.82) for diarrhoea, nausea/vomiting, bloating, loss of appetite, and weight loss, respectively. With the exception of bloating, odds were significantly lower for those on ARV containing integrase inhibitors and greater for patients reporting current cannabis use. GI symptoms in the modern ARV era are highly prevalent and may arise as a common pathway of distress in response to psychosocial vulnerabilities, regardless of the stage of diagnosis. These findings support the need for integrated approaches to address psychological and physical distress in HIV disease.

Adequacy of Mental Health Services for HIV-Positive Patients with Depression: Ontario HIV Treatment Network Cohort Study.

BackgroundMajor depression can profoundly impact clinical and quality-of-life outcomes of people living with HIV, and this disease is underdiagnosed and undertreated in many HIV-positive individuals. Here, we describe the prevalence of publicly funded primary and secondary mental health service use and antidepressant use, as well as mental health care for depression in accordance with existing Canadian guidelines for HIV-positive patients with depression in Ontario, Canada.MethodsWe conducted a prospective cohort study linking data from the Ontario HIV Treatment Network Cohort Study with administrative health databases in the province of Ontario, Canada. Current depression was assessed using the Center for Epidemiologic Depression Scale or the Kessler Psychological Distress Scale. Multivariable regressions were used to characterize prevalence outcomes.ResultsOf 990 HIV-positive patients with depression, 493 (50%) patients used mental health services; 182 (18%) used primary services (general practitioners); 176 (18%) used secondary services (psychiatrists); and 135 (14%) used both. Antidepressants were used by 407 (39%) patients. Patients who identified as gay, lesbian, or bisexual, as having low income or educational attainment, or as non-native English speakers or immigrants to Canada were less likely to obtain care. Of 493 patients using mental health services, 250 (51%) received mental health care for depression in accordance with existing Canadian guidelines.ConclusionsOur results showed gaps in delivering publicly funded mental health services to depressed HIV-positive patients and identified unequal access to these services, particularly among vulnerable groups. More effective mental health policies and better access to mental health services are required to address HIV-positive patient needs and reduce depression’s impact on their lives.

Central nervous system penetration effectiveness of antiretroviral drugs and neuropsychological impairment in the Ontario HIV Treatment Network Cohort Study.

Since the introduction of combination antiretroviral therapy (cART), the incidence of severe HIV-associated neurocognitive impairment has declined significantly, whereas the prevalence of the milder forms has increased. Studies suggest that better distribution of cART drugs into the CNS may be important in reducing viral replication in the CNS and in reducing HIV-related brain injury. Correlates of neuropsychological (NP) performance were determined in 417 participants of the Ontario HIV Treatment Cohort Study (OCS). All participants were on three cART drugs for at least 90days prior to assessment. Multiple logistic and linear regression methods were used. Most participants were Caucasian men with mean age of 47years. About two thirds had a nadir CD4+ T-cell count below 200cells/μL and 92% had an undetectable plasma HIV viral load. The median CNS penetration effectiveness (CPE) score was 7. Sixty percent of participants had neuropsychological impairment. Higher CPE values significantly correlated with lower prevalence of impairment in bivariate and multivariate analyses. In this cross-sectional analysis of HIV+ adults who had a low prevalence of comorbidities and were taking three-drug cART regimens, greater estimated distribution of cART drugs into the CNS was associated with better NP performance.

Validation of Six Short and Ultra-short Screening Instruments for Depression for People Living with HIV in Ontario: Results from the Ontario HIV Treatment Network Cohort Study.

ObjectiveMajor depression affects up to half of people living with HIV. However, among HIV-positive patients, depression goes unrecognized 60–70% of the time in non-psychiatric settings. We sought to evaluate three screening instruments and their short forms to facilitate the recognition of current depression in HIV-positive patients attending HIV specialty care clinics in Ontario.MethodsA multi-centre validation study was conducted in Ontario to examine the validity and accuracy of three instruments (the Center for Epidemiologic Depression Scale [CESD20], the Kessler Psychological Distress Scale [K10], and the Patient Health Questionnaire depression scale [PHQ9]) and their short forms (CESD10, K6, and PHQ2) in diagnosing current major depression among 190 HIV-positive patients in Ontario. Results from the three instruments and their short forms were compared to results from the gold standard measured by Mini International Neuropsychiatric Interview (the “M.I.N.I.”).ResultsOverall, the three instruments identified depression with excellent accuracy and validity (area under the curve [AUC]>0.9) and good reliability (Kappa statistics: 0.71–0.79; Cronbach’s alpha: 0.87–0.93). We did not find that the AUCs differed in instrument pairs (p-value>0.09), or between the instruments and their short forms (p-value>0.3). Except for the PHQ2, the instruments showed good-to-excellent sensitivity (0.86–1.0) and specificity (0.81–0.87), excellent negative predictive value (>0.90), and moderate positive predictive value (0.49–0.58) at their optimal cut-points.ConclusionAmong people in HIV care in Ontario, Canada, the three instruments and their short forms performed equally well and accurately. When further in-depth assessments become available, shorter instruments might find greater clinical acceptance. This could lead to clinical benefits in fast-paced speciality HIV care settings and better management of depression in HIV-positive patients.

High incidence of diagnosis with syphilis co-infection among men who have sex with men in an HIV cohort in Ontario, Canada.

BackgroundThe re-emergence of syphilis among HIV-positive gay and other men who have sex with men (MSM) requires vigilance. We estimated incidence of and risk factors for first and subsequent syphilis diagnoses among MSM in HIV care in Ontario, Canada.MethodsWe analyzed data from 2,280 MSM under follow-up from 2006 to 2010 in the Ontario HIV Treatment Network Cohort Study (OCS), a multi-site clinical cohort. We obtained syphilis serology results via record linkage with the provincial public health laboratory. Rates were calculated using Poisson regression.ResultsFirst syphilis diagnoses occurred at a rate of 2.0 per 100 person-years (95 % CI 1.7, 2.4; 121 cases) whereas the re-diagnosis rate was 7.5 per 100 person-years (95 % CI 6.3, 8.8; 136 cases). We observed higher rates over time and among men who were aged <30 years, receiving care in the two largest urban centers, or had a previous syphilis diagnosis. Syphilis diagnosis was less common among Indigenous men, men with higher CD4 cell counts, and, for first diagnoses only, among men with less than high school education.ConclusionsCompared to reported cases in the general male population, incidence of a new syphilis diagnosis was over 300 times greater among HIV-positive MSM but year-to-year changes reflected provincial trends. Re-diagnosis was common, suggesting treatment failure or re-infection. Novel syphilis control efforts are needed among HIV-positive MSM.

Implementation and Operational Research

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. 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. 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. 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.

Hepatitis C virus seroconversion among HIV-positive men who have sex with men with no history of injection drug use: Results from a clinical HIV cohort.

Internationally, there is a growing recognition that hepatitis C virus (HCV) may be sexually transmitted among HIV-positive men who have sex with men (MSM). To report the first Canadian estimate of HCV seroincidence in 2000 to 2010 and its risk factors among HIV-positive MSM with no known history of injection drug use. Data from the Ontario HIV Treatment Network Cohort Study, an ongoing cohort of individuals in HIV care in Ontario, were analyzed. Data were obtained from medical charts, interviews and record linkage with the provincial public health laboratories. The analysis was restricted to 1534 MSM who did not report injection drug use and had undergone ≥2 HCV antibody tests, of which the first was negative (median 6.1 person-years [PY] of follow-up; sum 9987 PY). In 2000 to 2010, 51 HCV seroconversions were observed, an overall incidence of 5.1 per 1000 PY (95% CI 3.9 to 6.7). Annual incidence varied from 1.6 to 8.9 per 1000 PY, with no statistical evidence of a temporal trend. Risk for seroconversion was elevated among men who had ever had syphilis (adjusted HR 2.5 [95% CI 1.1 to 5.5) and men who had acute syphilis infection in the previous 18 months (adjusted HR 2.8 [95% CI 1.0 to 7.9]). Risk was lower for men who had initiated antiretroviral treatment (adjusted HR 0.49 [95% CI 0.25 to 0.95]). There were no statistically significant effects of age, ethnicity, region, CD4 cell count or HIV viral load. These findings suggest that periodic HCV rescreening may be appropriate in Ontario among HIV-positive MSM. Future research should seek evidence whether syphilis is simply a marker for high-risk sexual behaviour or networks, or whether it potentiates sexual HCV transmission among individuals with HIV.