M Hull, A Cescon, JM Raboud, MB Klein , S Walmsley,

1. Switching from first ART regimen while virologically suppressed is common in the CANOC cohort and is associated with increased risk of subsequent virologic failure M Hull, A Cescon, JM Raboud, MB Klein, S Walmsley, E Ding, W Zhang, S Shurgold, N Machouf, AN Burchell, C Cooper, MR Loutfy, JSG Montaner, C Tsoukas, RS Hogg, CANOC Collaboration 20th International AIDS Conference Melbourne Australia July 2014

2. Disclosures • Supported by a Chercheur Nationaux award from the Fonds de Recherche Sante, Quebec (FRQ-S) • Received honoraria and acted as a consultant: • ViiV, Gilead, Janssen and Merck • Research funding from: • Merck and ViiV

3. Background Current first-line ART regimens are well-tolerated and associated with long-term virologic suppression Switching or modifying regimens is common for tolerability and convenience reasons In the early ART era 44% of individuals were found to modify their regimen at a single site1 Approximately 40% of individuals in the ART-CC analysis modified first-line ART between 2002-20092 1Mocroft A. AIDS 2001;15: 185. 2Abgrall S. AIDS 2013;27:803.

4. Rationale & Objectives • Outcomes after switching for tolerability are presumed to be similar to those who remain on first-line regimens • We aimed to evaluate the risk of virologic failure in people who switch for reasons other than virologic failure • Describe factors associated with regimen switch for reasons other than virologic failure

5. Cohort • CANOC is Canada’s largest pan-provincial HIV treatment cohort study • This collaboration focuses on evaluating the impact of antiretroviral care on the health of persons living with HIV across various regions of Canada • Participating cohorts (approx 10,000 pts): • BC Centre for Excellence in HIV/AIDS • Clinique Medicale l’Actuel • Immune Deficiency Treatment Centre (IDTC) • Maple Leaf Medical Clinic • Montreal Chest Institute IDS • OHTN Cohort Study (OCS) • Toronto General Hospital • University of Ottawa BC QC ON

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

7. Inclusion Criteria • For this analysis: • Started ART January 1, 2005 – June 30, 2012 • Achieved virologic suppression on ART • Defined as 2 plasma viral loads (pVL) < 50 copies/mL > 1 month apart • Subsequent regimen switch while suppressed • Within same class of ART • To different class of ART

8. Outcomes • Factors associated with regimen switch • Time to virologic failure (from first suppression)  Virologic failure defined as pVL > 1000 copies/mL

9. Statistical Methods Multinomial logistic regression model to assess factors associated with first and subsequent regimen switches Marginal Structural Model for risk of virologic failure after switch Time-varying switch as the primary variable of interest Time-varying CD4 cell count as time-dependent confounder Time fixed covariates: age, gender, IDU status, baseline CD4 count, province and calendar year of ART initiation

10. Baseline demographic and clinical characteristics (n=2807) Results *Results are median (Q1-Q3) or n (%).

11. Characteristics of Individuals with ART switch *Results are median (Q1-Q3) or n (%).

12. Multinomial Logistic Regression Analysis - Factors associated with single or multiple regimen switches

13. Results – Marginal Structural Model for regimen switch and risk of virologic failure

14. Discussion Even with modern ART, regimen switch while virologically suppressed was common, occurring in 36% of individuals Presumed toxicity/tolerability/simplification/DDI Switching was associated with longer duration of ART Switching ≥ 2 times was female gender Provincial differences in rates of switching (BC having more persons switching ≥2 times) Switching from first ART regimen while virologically suppressed was associated with subsequent virologic failure

15. Discussion • Switching ART for “tolerability” reasons might represent specific patient characteristics where ART intolerance is a marker for factors associated with poor adherence rather than with ART-agent specific concerns (e.g. IDU) • Women more likely to switch and to experience subsequent virologic failure-- may represent regimen changes around pregnancies

16. Limitations We could not identify specific reasons for switch We were unable to assess role of adherence We did not evaluate specific components of regimens being switched Virologic failure was defined by virologic rebound Development of associated resistance mutations has not yet been assessed

17. Conclusions • Regimen switching while virologically suppressed may not be completely benign • Closer follow up among patients switching for non-virologic reasons may be warranted as such switches may serve as a marker for problems with adherence or poorer tolerance of medications (e.g. women)

18. Thank you www.canoc.ca @CANOCresearch 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).