Characterizing Human Immunodeficiency Virus Antiretroviral Therapy Interruption and Resulting Disease Progression Using Population-Level Data in British Columbia, 1996-2015

Abstract

Background Suboptimal retention is among the biggest challenges to realize the full benefits of combination antiretroviral therapy (ART). We aimed to describe ART interruption patterns and identify determinants of disease progression while off ART in British Columbia, Canada. Methods with population-level data on ART utilization and laboratory testing in British Columbia (1996-2015), we described the timing, frequency, and duration of ART interruptions (a gap of ≥90 days in ART dispensation records). A 4-state continuous-time Markov model was implemented to identify determinants of disease progression during individuals' first ART interruption episode. Disease progression was measured according to CD4-based state transitions (cells/μL: ≥500 to 200-499; 200-499 to <200; ≥500 to death; 200-499 to death; and <200 to death). Results Among individuals initiating ART, 3129 (38.6%) interrupted ART over a median 8-year follow-up (interquartile range [IQR], 4.3-13.5 years). Those interrupting ART had a median of 1 interruption (IQR, 1.0-3.0), with the first interruption occurring 12.8 (IQR, 4.0-36.1) months after ART initiation, lasting for 7.5 (IQR, 4.1-20.3) months. The proportion of individuals interrupting ART within the first year of ART initiation decreased over time; however, the absolute number of individuals interrupting ART remained high. In a multivariable analysis, age, historical plasma viral load, and ART regimen changes prior to interruption were associated with increased hazard of CD4 decline and death. Conclusions Our results demonstrate that ART interruptions are common even in a high-resource setting with universal free access to human immunodeficiency virus care. Further efforts are needed to promote ART reengagement and may consider prioritizing individuals with poorer prognostic factors.