Determinants of discontinuation of initial highly active antiretroviral therapy regimens in a USHIV-infected patient cohort

Objectives Optimization of initial highly active antiretroviral therapy (HAART) for complete viral suppression and better tolerability is paramount for the prognosis of HIV-infected patients. Observational studies provide a better means than clinical trials of studying the determinants of discontinuation in actual practice. Methods A longitudinal cohort of US HIV-positive patients who initiated HAART for the first time from 1996 to 2003 were included in the analysis. Stratified Cox proportional hazards models, considering time-updated viral load and CD4 count data, were developed for analyzing time to first discontinuation. Results A total of 3414 antiretroviral-naive HAART patients were identified. In a median follow-up period of 211 days (mean 324 days), 628 patients (18.4%) reportedly discontinued the HAART regimen because of drug toxicity, 456 (13.4%) because of non-compliance, and 257 (7.5%) because of treatment failure. In addition to the recorded reasons for discontinuation, black ethnicity [relative risk (RR) 1.28, 95% confidence interval (CI) 1.13-1.45], current smoking (RR 1.33, CI 1.18-1.50), high pill burden (RR 1.44, CI 1.22-1.70), and recent viral control (RR 0.63, CI 0.56-0.70) were all predictive of discontinuation. Only high pill burden (> 15 pills/day), which is considered to be a surrogate for treatment regimen complexity, and the most recent poor viral control (HIV RNA) were found to be consistently associated with a higher likelihood of discontinuation. Conclusions Risk factors other than physician- or patient-reported reasons play a role in discontinuation of initial HAART regimens. Identification of these risk factors and simplification of treatment regimens in those at high risk for discontinuation appear to be necessary in order to maximize the effectiveness of HAART regimens.