Background Sustained optimal use of combination antiretroviral treatment (cART) has been shown to decrease morbidity mortality and HIV transmission. consecutive days off cART. We used descriptive analyses to study TI trends over time and Cox regression to identify factors predicting time to first TI and time to treatment resumption after a first TI. Results 7 633 participants were eligible of whom 1 860 (24.5%) experienced a TI. The prevalence of TI in the first calendar year of cART decreased by half over the study period. Our analyses highlighted GSK J1 a higher risk of TI among women (adjusted hazard ratio (aHR): 1.59 95 1.33 younger individuals (aHR: 1.27 95 1.15 per decade increase) earlier treatment initiators (CD4 count ≥350 versus <200 mm3 aHR: 1.46 95 1.17 Aboriginal participants (aHR: 1.67 95 1.27 injecting drug users (aHR: 1.43 95 1.09 and users of zidovudine versus tenofovir in the initial cART regimen (aHR: 2.47 95 1.92 Conversely factors predicting treatment resumption were male sex older age and a CD4 cell count <200 mm3 at cART initiation. Conclusion Despite significant improvements in cART since its advent our results demonstrate that TIs remain relatively prevalent. Strategies to support continuous HIV treatment are needed to maximize the benefits of cART. Mmp19 Keywords: Treatment interruption HIV antiretroviral therapy retention Canada Introduction The expanded use of combination antiretroviral therapy (cART) since 1996 has dramatically enhanced the quality of care and the life expectancy of HIV-positive individuals . However sustained optimal use of cART is necessary to ensure maximum therapeutic benefits. Incomplete adherence and treatment interruptions (TIs) due to treatment fatigue side effects and cART toxicities [2-4] have emerged as major challenges to the full realization of the therapeutic promise of cART effectiveness. Explored as a strategy to reduce cost and cART-related toxicities and improve patient quality of life TIs whether physician-directed (structured) or patient-initiated (unstructured) have been found to promote viral rebound and CD4 cell loss and more importantly to increase the risk of opportunistic infections and death in observational studies and prospective clinical trials [5-14]. As evidence GSK J1 accumulated demonstrating the adverse effects of TIs culminating in the publication of results from the seminal SMART trial in 2006  TIs were no longer recommended. However results from several studies indicate that unstructured patient-elected TIs continue to occur [5 16 17 Despite the relatively high frequency of TIs their determinants and outcomes from the year 2000 onwards a time period often characterized as the era of modern cART [16 18 and since 2006 when treatment recommendations were developed that precluded physician-directed TIs are still not well-characterized . As the paradigm of “treatment as prevention” and universal treatment become entrenched in contemporary treatment guidelines in North America [19-22] and globally  it is vital that we minimize the occurrence of TIs. In particular GSK J1 the World Health Organization’s revised guidelines effectively increase the number of individuals eligible for treatment globally by 50%  providing an urgent impetus to better understand and address TIs. Thus we conducted the present analysis to characterize trends and determinants of treatment interruption and resumption in a Canadian setting of universal free access to HIV care including medical and laboratory monitoring as well as cART. We hypothesized that individuals who are intermittent or episodic users of cART (defined here as those with gaps in cART of at GSK J1 least 90 days [5 10 24 are different from continuous users. Moreover we hypothesized that TIs should be less common than in previous studies due to improvements in cART profiles over time. We also assessed characteristics of individuals more likely to reinitiate cART once interrupted. Methods Study Population The Canadian Observational Cohort (CANOC) collaboration is a national collaboration of eight cohorts situated in three provinces (British Columbia (BC) Quebec and Ontario) of antiretroviral-naive HIV-positive individuals initiating cART after January 1 2000 The cohort has been described in more detail elsewhere . Briefly patient eligibility criteria for inclusion into CANOC are documented HIV infection.