ObjectivesTimely 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.MethodsThe 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 3 months of HIV diagnosis], delayed presentation (≥ 3 months from HIV diagnosis to presentation to care), and late presentation (CD4 count < 350 cells/μL or ADC within 3 months of presentation). We identified characteristics associated with these outcomes and explored their overlap.ResultsA 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.ConclusionsLate 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.

Introduction Incidence of syphilis, chlamydia and gonorrhoea continue to rise among HIV-positive men who have sex with men (MSM) in Ontario. We previously observed an elevated risk of sexually transmitted infections (STI) among recreational drug users. Our aim was to determine the effect of a new STI diagnosis and recreational drug use on virologic failure (VF) among MSM successfully treated with antiretroviral therapy (ART). Our hypothesis is that any association between STIs and VF would be confounded by drug use. Methods The OHTN Cohort Study follows people receiving HIV care in Ontario. STI results and viral load (VL) data were retrieved via linkage with the provincial laboratory. We restricted analyses to 2610 MSM who completed>=1 annual questionnaire in 2008–2014 and had two consecutive VL<50 within a six-month period on ART. VF was defined as a single VL>=1000 or two consecutive VLs>=200. Periods of STI exposure were set around the diagnosis dates for each STI. We modelled STI diagnosis exposures and drug use as time-varying covariates on risk of VF using Cox regression adjusting for age, region and income as confounders. Our model allowed for repeat STI exposures and repeated VF events using the marginal means/rates model. Results There were 472 VFs with a 24 month cumulative incidence of 12.1% (95%CI 11.1, 13.1). VFs at time of a new chlamydia or gonorrhoea infection were close to nil. We did not observe an increased risk of VF at the time of a new syphilis infection (HR=1.2 95% CI 0.8, 2.0; aHR=1.1 95% CI 0.7, 1.7). Risk was higher among drug users (non-injection aHR=1.4 95% CI 1.1, 1.8; injection aHR=1.8 95% CI 1.1, 2.6). There was no significant interaction but some evidence of positive confounding between syphilis and VF by drug use. Conclusion Regardless of drug use, we did not find an association between a new STI diagnosis and increased risk of VF among men on suppressive ART. Our data are limited by possible misclassification of STI exposures, because not all men were tested, and among those diagnosed, exact dates of acquisition were unknown.

Objectives Rates of chlamydia and gonorrhoea have been rising in urban centres in Canada, particularly among HIV-positive men who have sex with men (MSM). Our objective was to identify behavioural risk factors for diagnosis with chlamydia and gonorrhoea in this population, with a focus on the HIV status of sexual partners. Methods The OHTN Cohort Study follows people in HIV care across Ontario. We restricted the analysis to 1997 MSM who completed questionnaires in 2010–2013 at one of seven clinics that submit all chlamydia and gonorrhoea tests to the provincial public health laboratory; we obtained test results via record linkage. We estimated cumulative incidences using Kaplan–Meier methods and identified risk factors for diagnosis of a composite outcome (chlamydia or gonorrhoea infection) using Cox regression. Results At follow-up, there were 74 new chlamydia/gonorrhoea diagnoses with a 12-month cumulative incidence of 1.7% (95% CI 1.1% to 2.2%). Risk factors for chlamydia/gonorrhoea diagnosis were: 5+ HIV-positive partners (HR=3.3, 95% CI 1.4 to 7.8; reference=none) and recreational drug use (HR=2.2, 95% CI 1.2 to 3.9). Conclusions Heightened risks with recreational drug use and multiple HIV-positive partners suggest that chlamydia/gonorrhoea may have achieved high prevalence in certain sexual networks among HIV-positive MSM. Interventions to promote safer sex and timely testing among MSM are needed.

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

1 Réseau ontarien de traitement du VIH, Université de Toronto, Toronto (Ontario) 2 Département de psychiatrie, Université de Toronto, Toronto (Ontario) 3 Centre for Research on Inner City Health, Li Ka Shing Knowledge Institute de l’hôpital St. Michael’s, Toronto (Ontario) 4 Bureau de lutte contre le sida du ministère ontarien de la Santé et des Soins de longue durée, Toronto (Ontario) 5 Dalla Lana School of Public Health, Université de Toronto, Toronto (Ontario)

Investments in community-based HIV prevention programs in Ontario over the past two and a half decades are assumed to have had an impact on the HIV epidemic, but they have never been systematically evaluated. To help close this knowledge gap, we conducted a macro-level evaluation of investment in Ontario HIV prevention programs from the payer perspective. Our results showed that, from 1987 to 2011, province-wide community-based programs helped to avert a total of 16,672 HIV infections, saving Ontario's health care system approximately $6.5 billion Canadian dollars (range 4.8-7.5B). We also showed that these community-based HIV programs were cost-saving: from 2005 to 2011, every dollar invested in these programs saved about $5. This study is an important first step in understanding the impact of investing in community-based HIV prevention programs in Ontario and recognizing the impact that these programs have had in reducing HIV infections and health care costs.

BACKGROUND: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).OBJECTIVE: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.METHODS: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).RESULTS: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.CONCLUSIONS: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.

BACKGROUND:The 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. METHODS:We 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. RESULTS:First 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. CONCLUSIONS:Compared 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.

There is new hope that we can significantly reduce HIV rates. The United Nations AIDS organization, UNAIDS, has challenged all countries to strive for aggressive targets that could significantly bend the curve on HIV infections and deaths: 90% of people living with HIV diagnosed; 90% of people diagnosed on treatment; and 90% of people on treatment virally suppressed. This new optimism is largely driven by strong research findings that early and ongoing HIV treatment improves individual health outcomes and reduces people's viral load, making them less infectious. However, the risk of HIV infection is far from evenly distributed among populations most at risk. Those most at risk will find it hardest to reach these targets as they are caught in a syndemic (synergistic epidemic) of intertwining health and social issues. Our research, and that of others, shows that those who are in a syndemic of co-occurring mental health, addiction and social issues (e.g. homelessness, food insecurity) are significantly more likely to fall out of care, less likely to adhere to treatment and less likely to achieve/maintain an undetectable viral load. Intervention studies have found that a combination approach to HIV prevention and treatment that goes beyond primary care and mental health tools to include social and structural interventions has a protective effect, and can reduce risk and improve adherence. People living with and at risk of HIV need better access to social and mental health services as well as clinical treatment services that will help them achieve and maintain optimal health and well-being. We strongly encourage those in the HIV sector across the country to identify a common vision, with clear goals and targets. With concerted and targeted efforts, a focus on program and implementation science, and a willingness to see and treat HIV as a social as well as a biomedical problem-the fourth decade of HIV in Canada could well be the last.

Objectives We described patterns of testing for chlamydia and gonorrhoea infection among persons in specialty HIV care in Ontario, Canada, from 2008 to 2011.Methods We analysed data from 3165 participants in the OHTN Cohort Study attending one of seven specialty HIV care clinics. We obtained chlamydia and gonorrhoea test results via record linkage with the provincial public health laboratory. We estimated the proportion of participants who underwent testing annually, the positivity rate among those tested and the proportion diagnosed with chlamydia or gonorrhoea among all under observation. We explored risk factors for testing and diagnosis using multiple logistic regression analysis.Results The proportion tested annually rose from 15.2% (95% CI 13.6% to 16.7%) in 2008 to 27.0% (95% CI 25.3% to 28.6%) in 2011 (p<0.0001). Virtually all were urine-based nucleic acid amplification tests. Testing was more common among men who have sex with men (MSM), younger adults, Toronto residents, persons attending primary care clinics and persons who had tested in the previous year or who had more clinic visits in the current year. We observed a decrease in test positivity rates over time. However, the annual proportion diagnosed remained stable and in 2011 this was 0.97% (95% CI 0.61% to 1.3%) and 0.79% (95% CI 0.46% to 1.1%) for chlamydia and gonorrhoea, respectively. Virtually all cases were among MSM.Conclusions Chlamydia and gonorrhoea testing increased over time while test positivity rates declined and the overall proportion diagnosed remained stable, suggesting that the modest increase in testing did not improve case detection.

Background: The risk of sexual HIV transmission in serodiscordant couples when the HIV-positive partner has full virologic suppression on combination antiretroviral therapy (cART) is debated. This study aims to systematically review observational studies and randomized controlled trials (RCTs), evaluating rates of sexual HIV transmission between heterosexual serodiscordant couples when the HIV-positive partner has full suppression on cART.Methods and Findings: We searched major bibliographic databases to November 2012 for relevant observational studies and RCTs without language restrictions. Conference proceedings, key journals and bibliographies were also searched. Studies reporting HIV transmission rates, cART histories and viral loads of the HIV-positive partners were included. Two reviewers extracted methodologic characteristics and outcomes. Of 20,252 citations, 3 studies met all eligibility criteria with confirmed full virologic suppression in the HIV-positive partner. We included 3 additional studies (2 cohort studies, 1 RCT) that did not confirm viral suppression in the HIV-positive partner at transmission in a secondary meta-analysis. Methodologic quality was reasonable. The rate of transmission in the 3 studies confirming virologic suppression was 0 per 100 person-years (95% CI = 0-0.05), with low heterogeneity (I-2 = 0%). When we included the 3 studies that did not confirm virologic suppression, the rate of transmission was 0.14 per 100 person-years (95%CI = 0.04-0.31) (I-2 = 0%). In a sensitivity analysis including all 6 studies, the rate of transmission was 0 per 100 person-years (95%CI = 0-0.01) after omitting all transmissions with known detectable or unconfirmed viral loads, as full suppression in these cases was unlikely. Limitations included lack of data on same-sex couples, type of sexual intercourse (vaginal vs. anal), direction of HIV transmission, exact viral load at the time of transmission, sexually transmitted infections (STI) rates, and extent of condom use.Conclusions: Our findings suggest minimal risk of sexual HIV transmission for heterosexual serodiscordant couples when the HIV-positive partner has full viral suppression on cART with caveats regarding information on sexual intercourse type, STIs, and condom use. These findings have implications when counseling heterosexual serodiscordant couples on sexual and reproductive health. More research is needed to explore HIV transmission risk between same-sex couples.

Background There is evidence of sexual HCV transmission among HIV-positive MSM from the UK and Europe. We estimated HCV seroincidence and its risk factors in a North American population of HIV-positive MSM with no known history of injection drug use. Methods We analysed data from the OHTN Cohort Study, an ongoing cohort of persons in HIV care in Ontario, Canada. Data were obtained from medical charts, interviews, and record linkage with the provincial public health laboratories. We restricted the analysis to 1,534 MSM who: (1) did not report injection drug use; (2) were under follow-up in 2000–2010; and (3) had 2+ HCV antibody tests, of which the first was negative. Person-time commenced at the later of the HCV-negative result or HIV diagnosis and ended at the first HCV+ or last date of follow-up (median 6.1 person-years (PY) of follow-up; sum 9,987PY). Results We observed 51 HCV seroconversions, for an overall incidence of 0.51 per 100PY (CI: 0.39–0.67). Annual incidence varied from 0.16 to 0.89 per 100 PY, with no statistical evidence of a temporal trend. Seroconversion was statistically-significantly associated with acute syphilis infection in the previous 6 months (adjusted hazard ratio = 4.9, CI 1.2–21) and there was a marginally statistically-significant association for men who had not yet initiated antiretroviral treatment (adjusted hazard ratio = 1.9, CI 0.91–4.0). There were no statistically significant effects of age, ethnicity, region, CD4+ cell count or viral load. Conclusion Sexual behaviour was unmeasured and we cannot exclude the possibility of HCV acquisition via unreported injection drug use. Nevertheless, the strong association with recent syphilis suggests that at least some cases were due to sexual transmission. Future research is needed to establish whether syphilis is a marker for high-risk behaviour or may potentiate sexual HCV transmission among persons with HIV.

Since 2000, reported syphilis cases increased ten-fold in Canada, particularly among men who have sex with men (MSM) co-infected with HIV. We characterized temporal patterns of of syphilis testing in a large cohort of HIV patients in Ontario, Canada.

African and Caribbean communities in Canada and other developed countries are disproportionately affected by HIV/AIDS. This qualitative study of African and Caribbean communities in Toronto sought to understand HIV-related stigma, discrimination, denial and fear, and the effects of multiple intersecting factors that influence responses to the disease, prevention practices and access to treatment and support services. Semi-structured interviews were conducted with 30 HIV-positive men and women and focus groups were conducted with 74 men and women whose HIV status was negative or unknown. We identified a range of issues faced by African and Caribbean people that may increase the risk for HIV infection, create obstacles to testing and treatment and lead to isolation of HIV-positive people. Our findings suggest the need for greater sensitivity and knowledge on the part of healthcare providers; more culturally specific support services; community development; greater community awareness; and expanded efforts to tackle housing, poverty, racism and settlement issues.

Plain Language Summary: This paper examines available evidence on the number of people with HIV in Russia who require treatment (over 20,000 and a figure that will rapidly increase in the near future) and compares that to the estimated number of those receiving treatment (no more than 2000). The paper examines the various barriers to treatment in Russia, including cost, lack of political will, stigma, and a poorly developed capacity to treat. The paper then considers the various opportunities that may be available to Russia to increase access to treatment, including increased capacity to negotiate price reductions, efforts to increase domestic production or import generics, and efforts to build the political will to address Russia's treatment needs.