The purpose of this study was to describe the variability in highly active antiretroviral therapy (HAART) regimens over time, the extent to which individuals switch, and the characteristics of those who are switching.We evaluated data collected between 1994 and 2000 from 1056 HIV-positive women enrolled in the Women's Interagency HIV Study (WIHS) who reported initiating HAART. We described the variability and prevalence of changes in HAART regimens between semiannual visits, estimated time to switch using Kaplan-Meier methods, investigated factors associated with a first switch using Cox proportional hazards models, and compared disease markers among women switching or remaining on unchanged HAART regimens.We demonstrated a 13-fold increase in the number of unique HAART regimens reported since mid-1996 and showed that the amount of time spent on the first, second, or third regimen is similar, with an 8-month median time to switching or discontinuing the initial HAART regimen. Women who switched had a lower mean CD4 cell count and were more likely to have HIV RNA levels greater than 400 copies/mL. Overall, the percentage of women switching decreased over the course of follow-up (to 37% in September 2000), although the percentage discontinuing therapy altogether increased 2-fold.Our findings on the relatively high rate of HAART switching emphasize the complexity of managing and evaluating these therapies.