TRENDS, PREDICTORS AND OUTCOMES ASSOCIATED WITH UNSTRUCTURED TREATMENT INTERRUPTIONS AMONG HIV-POSITIVE INDIVIDUALS ON ANTIRETROVIRAL THERAPY IN CANADA
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Background The expanded use of combination antiretroviral therapy (cART) has dramatically enhanced the quality of care and life expectancy of HIV-positive individuals. However, incomplete adherence and treatment interruptions (TIs) due to treatment fatigue, side effects and cART toxicities have emerged as major challenges to the full realization of the therapeutic promise of cART. Despite the relatively high frequency of TIs, their determinants and outcomes are still not well-characterized. Methods Trends, predictors and consequences of treatment interruption (TI) and resumption in two study populations were estimated. First, the Longitudinal Investigations into Supportive and Ancillary health services (LISA) is a cross-sectional study of hard-to-reach individuals on cART in British Columbia. Between 2007 and 2010, 1000 participants were interviewed about sociodemographic and clinical factors. Using pharmacy recording, TIs were defined as a patient-initiated interruption in treatment of at least 90 days during the 12 months preceding or following the study interview. Multivariable logistic regression was used to identify factors associated with treatment interruption. The second study, the Canadian Observational Cohort (CANOC) collaboration, is composed of treatment-naïve HIV-positive individuals who initiated cART between 2000-2011. TIs were defined as interruptions in cART for a period of at least 90 days. Cox proportional hazards regression was used to identify determinants and consequences of cART interruption and resumption. Results Of 768 participants included in the LISA study, 15% had a TI recorded during the study window. In multivariable analysis, TIs were significantly associated with current illicit drug use (adjusted odds ratio (aOR): 1.68, 95% confidence interval [CI]: 1.05-2.68); <95% adherence in the first year of treatment (aOR: 2.68, 95% CI: 1.67-4.12); living with more than one person (aOR: 1.95; 95% CI: 1.22-3.14) or on the street (aOR: 5.08, 95% CI: 1.72-14.99) compared to living alone; poor perception of overall health (aOR: 1.64 95% CI: 1.05-2.55); being unemployed (aOR: 2.22, 95% CI: 1.16-4.23); and younger age at interview (aOR: 0.57, 95% CI: 0.44-0.75, per 10 year increment). A total of 7,633 CANOC participants initiating cART between 2000 and 2011, of whom 1,860 (24.5%) had at least one TI ≥90 days. The prevalence of TI in the first calendar year of cART decreased by half over the study period. Predictors of a first TI were female sex (adjusted hazard ratio (aHR): 1.59, 95% CI: 1.33-1.92), Aboriginal ancestry (aHR: 1.67, 1.27-2.20), a history of injecting drug use (aHR: 1.43, CI: 1.09-1.89), hepatitis C antibody seropositivity (aHR: 2.17, CI: 1.68-2.79), a baseline CD4 cell count above 350 cells/mm3 versus less than 200 cells/mm3 (aHR: 1.46, CI: 1.17-1.81) and use of zidovudine versus tenofovir in the initial cART regimen (aHR: 2.47, CI: 1.92-3.20). Factors protective against TI were older age (aHR: 0.79, CI: 0.73-0.87), higher HIV plasma viral load (log10) (aHR: 0.87, CI: 0.78-0.97) and residence in Ontario (aHR: 0.55, CI: 0.43-0.70) or Quebec (aHR: 0.42, CI: 0.31-0.57) versus British Columbia (BC). Factors predicting resumption of treatment after a first TI included male sex, residence in BC, older age, more recent cART initiation and a CD4 cell count <200 cells/mm3 at cART initiation (all p<0.05). TIs were associated with increased risk of mortality (aHR: 1.79, CI: (1.49-2.16)) after adjusting for socio-demographic and clinical factors. Conclusions Despite significant improvements in cART since its advent and the decreasing prevalence of TIs, gaps in treatment remain relatively common. As cART is propagated at increasing levels globally, and the impetus to provide treatment earlier in the course of HIV infection for individual and public health benefits gains momentum, ensuring continuity of treatment becomes even more vital. Strategies to support continuous HIV treatment are needed to maximize the benefits of cART.