1. Late initiation of combination antiretroviral therapy in Canada, 2000-2012: A call for a broad national public health strategy to improve engagement in HIV care Cescon A, Patterson S, Davey C, Chan K, Raboud JM, Loutfy MR, Cooper C, Burchell AN, Tsoukas C, Machouf N, Klein MB, Rachlis A, Rourke SB, Hogg RS, Montaner JSG, CANOC Collaboration Northern Health Research Conference June 6, 2015 Timmins, Ontario

2. Conflict of Interest Declaration I have no financial or personal relationships to disclose 2

3. Background HIV continues to be a public health concern in Canada As of 2011, an estimated 71,300 Canadians were living with HIV 26% remain undiagnosed With long-term combination antiretroviral therapy (ART) use, life expectancy for HIV-positive persons is approaching that of general population 1 ART suppresses the virus to undetectable levels and restores immune function (increases CD4 cell count); additional secondary benefit of preventing HIV transmission 3 1 Samji et al., 2013

4. Background 4 Initiation of ART with low CD4 cell counts or AIDS-defining illnesses increases the risk of poor treatment outcomes and mortality Figure: Life expectancy estimates at age 20, overall and by baseline CD4 count 1 1 Samji et al., 2013

5. Guidelines: When to start ART? Year(s)Primary guideline (recommended) 1996 CD4 500 if VL ≥30000 or ADI 1997-1999 VL >5000 or ADI 2000-2001 CD4 500 if VL ≥30000 or ADI 2002-2007 CD4 ≤200 or ADI 2008-2009 CD4 ≤350 or ADI 2010-2011CD4 ≤500 or ADI 2012 onwardsAll patients ADI, AIDS-defining illness; VL, HIV viral load 5

6. Rationale & Objectives 6 Despite substantial evidence supporting the benefits of early initiation of ART, HIV continues to be diagnosed and subsequently treated later than contemporary guidelines recommend in many settings Using a multi-site Canadian cohort we aim to: (1) Characterize the timing of ART initiation over time, and (2) Determine factors associated with “late” initiation of treatment

7. Primary Outcomes 7 1. Timing of ART initiation: determined by the CD4 cell count of participants at first initiation of ART 1. Late initiation: defined as a baseline CD4 cell count <200 cells/mm 3 or a baseline AIDS-defining illness

8. Canadian Observational Cohort (CANOC) Established in 2007, CANOC is Canada’s largest pan- provincial HIV treatment cohort study Participating sites: BC Centre for Excellence in HIV/AIDS Clinique Medicale l’Actuel Immune Deficiency Treatment Centre Maple Leaf Medical Clinic Montreal Chest Institute IDS OHTN Cohort Study (OCS) University Health Network Ottawa Hospital Immunodeficiency Clinic Newfoundland HIV Cohort Study Regina Qu’Appelle HIV Cohort 8

9. Inclusion Criteria CANOC: ≥ 18 years old with first ART therapy date ≥ January 1 st, 2000 Live in Canada Started ART with at least 3 individual agents naively (i.e., no prior antiretroviral experience) Available baseline CD4 and viral load results within six months of starting therapy 9

10. Statistical Methods Temporal trends were assessed using the Cochran- Armitage test Demographic and clinical variables were compared by late initiation vs. not using the Pearson χ 2 test or Fisher’s exact test for categorical variables and Wilcoxon rank-sum test for continuous variables Factors independently associated with late initiation were identified using logistic regression 10

11. Baseline demographic and clinical characteristics (n=9997) CharacteristicMedian (Q1-Q3) or % Age40 (33-47) Female18% Province British Columbia46% Ontario34% Quebec20% Aboriginal ancestry8% HCV co-infection27% CD4 count (cells/mm 3 ) 228 (125-335) HIV viral load (log 10 copies/mL) 4.8 (4.3-5.0) Results HCV, hepatitis C virus 11

12. Distribution and median of CD4 cell counts at ART initiation in CANOC, 2000-2012 (n=9997) ART, combination antiretroviral therapy 200 360 12

13. Median baseline CD4 cell counts at ART initiation by province, 2000-2012 (n=9997) ART, combination antiretroviral therapy 13

14. Percentage with late ART initiation, 2000-2012 (n=9997) ART, combination antiretroviral therapy; ADI, AIDS-defining illness 47% 14

15. 15 # Odds ratio per incremental year of calendar time Factors associated with late ART initiation, 2000-2012

16. Discussion We report a significant increase in CD4 cell counts at primary ART initiation among participants of a large Canadian HIV cohort collaboration over the twelve-year study period (2000-2012) However, CD4 cell counts at ART initiation remain below contemporary treatment guidelines 47% of participants initiating ART in 2012 starting ‘late’ Important correlates of late ART initiation were identified: Female sex, older age, residence in Ontario or BC (vs. Québec), HCV co-infection, earlier year of ART initiation These findings contribute to a better understanding of the timing of ART commencement across Canada and support the expansion of healthcare engagement strategies 16

17. Discussion: Late Diagnosis? An important contributing factor Undiagnosed HIV infections in Canada – 26% HIV infection HIV diagnosis Linked to HIV care Retained in HIV care Need ARTOn ART Adherent & suppressed Gardner et al., 2011 17

18. Discussion: Late Diagnosis? An important contributing factor Undiagnosed HIV infections in Canada – 26% Figure: Proportion of undiagnosed HIV infection in Canada by risk category 1 IDU, injection drug use; MSM, men who have sex with men 1 PHAC, 2011

19. Practice Implications In Canada, the offering of HIV testing during routine clinical encounters remains largely based on perceived risks (“risk-based” testing) Hinders diagnosis opportunities and contributes to ongoing stigmatization related to HIV testing We recommend the consideration of strategies that include the regular and routine offering of testing, irrespective of perceived or identified risks BC: implementation of routine HIV testing Family medicine, ED, inpatient 19

20. Limitations Data were obtained from only 3 provinces and are not generalizable to all HIV-positive persons in Canada BC data represents the entire sample of people on ART in the province, while data from ON and QC are based on a selection of clinics Missing data for select variables 20

21. Conclusions Our results demonstrate that CD4 counts at ART initiation remain below contemporary treatment guidelines These findings contribute to a better understanding of the timing of ART commencement across Canada, and should help to inform the implementation of improved healthcare engagement strategies We advocate for expanded HIV testing programs and the development of Canadian consensus guidelines as a useful next step to provide uniform, evidence-based clinical directives for HIV management across Canada 21

22. We would like to thank all of the participants for allowing their information to be a part of CANOC. CANOC is supported by the Canadian Institutes of Health Research (CIHR) and the CIHR Canadian HIV Trials Network (CTN 242). The CANOC Collaboration includes: Gloria Aykroyd (Ontario HIV Treatment Network), Louise Balfour (University of Ottawa, Contributes to the Ontario HIV Treatment Network), Ahmed Bayoumi (University of Toronto, Contributes to the Ontario HIV Treatment Network), John Cairney (University of Toronto, Contributes to the Ontario HIV Treatment Network), Liviana Calzavara (University of Toronto, Contributes to the Ontario HIV Treatment Network), Angela Cescon (British Columbia Centre for Excellence in HIV/AIDS), Curtis Cooper (University of Ottawa, Contributes to the Ontario HIV Treatment Network), Fred Crouzat (Maple Leaf Medical Clinic), Kevin Gough (University of Toronto, Contributes to the Ontario HIV Treatment Network), Silvia Guillemi (British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia), Richard Harrigan (British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia), Marianne Harris (British Columbia Centre for Excellence in HIV/AIDS), George Hatzakis (McGill University), Robert Hogg (British Columbia Centre for Excellence in HIV/AIDS, Simon Fraser University), Sean Hosein (CATIE), Don Kilby (University of Ottawa, Ontario HIV Treatment Network), Marina Klein (Montreal Chest Institute Immunodeficiency Service Cohort, McGill University), Richard Lalonde (The Montreal Chest Institute Immunodeficiency Service Cohort and McGill University), Viviane Lima (British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia), Mona Loutfy (University of Toronto, Maple Leaf Medical Clinic), Nima Machouf (Clinique Medicale l’Actuel, University de Montreal), Ed Mills (British Columbia Centre for Excellence in HIV/AIDS, University of Ottawa), Peggy Millson (University of Toronto, Contributes to the Ontario HIV Treatment Network), Julio Montaner (British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia), David Moore (British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia), Alexis Palmer (British Columbia Centre for Excellence in HIV/AIDS), Janet Raboud (University of Toronto, University Health Network), Anita Rachlis (University of Toronto, Contributes to the Ontario HIV Treatment Network), Stanley Read (University of Toronto, Contributes to the Ontario HIV Treatment Network), Sean Rourke (Ontario HIV Treatment Network, University of Toronto), Marek Smieja (McMaster University, Contributes to the Ontario HIV Treatment Network), Irving Salit (University of Toronto, Contributes to the Ontario HIV Treatment Network), Darien Taylor (Canadian AIDS Treatment Information Exchange Contributes to the Ontario HIV Treatment Network), Benoit Trottier (Clinique Medicale l’Actuel, University de Montreal), Chris Tsoukas (McGill University), Sharon Walmsley (University of Toronto, Contributes to the Ontario HIV Treatment Network), and Wendy Wobeser (Queen’s University, Contributes to the Ontario HIV Treatment Network). Thank you 22

23. For more information please visit: www.canoc.ca @CANOCresearch Contact: acescon@nosm.ca 23