BACKGROUND:: Reported reasons for change or discontinuation of antiretroviral therapy (δART) include adverse events, intolerability, and nonadherence. Little is known how reasons for δART differ by gender. METHODS:: In a retrospective cohort study, rates and reasons for δART alterations in a large University-based HIV clinic cohort were evaluated. Logistic regression analyses were used to evaluate the relationship between reasons for δART and gender. Cox proportional hazard models were used to investigate time to δART. RESULTS:: In total, 631 HIV-positive individuals were analyzed. Women (n = 164) and men (n = 467) were equally likely (53.0% and 54.4%, respectively) to discontinue treatment within 12 month of initiating a new regimen. Reasons for δART, however, were different based on gender-women were more likely to δART due to poor adherence [adjusted odds ratio (OR), 1.44; 95% confidence interval (CI): 0.85 to 2.42], dermatologic symptoms (adjusted OR, 2.88; 95% CI: 1.01 to 8.18), neurological reasons (adjusted OR, 1.82; 95% CI: 0.98 to 3.39), constitutional symptoms (adjusted OR, 2.23; 95% CI: 1.10 to 4.51), and concurrent medical conditions (adjusted OR, 2.03; 95% CI: 1.00 to 4.12). CONCLUSIONS:: Although the rates of δART are similar among men and women in clinical practice, the reasons for treatment changes are different based on gender. The potential for unique patterns of adverse events and poor adherence among women requires further investigation. Copyright © 2009 by Lippincott Williams & Wilkins.