OBJECTIVES: Highly active antiretrovial therapy (HAART) is a mainstay of treatment for patients with Human Immunodeficiency Virus (HIV).  Given that lower HAART pill burdens have been shown to be associated with an increased duration of initial therapy, there is a need to understand the effect of daily pill burden on the duration of the initial regimen.  The objective of this study was to estimate the effects of daily pill burden on the time to discontinuation of the initial HAART regimen.  METHODS: A retrospective cohort design was used where adult, female, HIV-positive patients initiating therapy at the study clinic were included.  A Kaplan-Meier curve was generated and a Cox proportional hazards model was developed to assess the impact of patient, regimen, and demographic characteristics on the hazard of discontinuation of the initial regimen.  RESULTS: A total of 498 charts were reviewed, yielding a cohort of 115 adult female patients who initiated HAART at the study clinic.  All study subjects were followed up from the initiation of HAART to treatment discontinuation.  Patients treated with a 1 pill/day regimen had a significantly longer time to discontinuation than regimens of 2+ pills/day (mean duration of initial therapy 1574.97 days vs. 977.48 days, respectively, p=0.003). Compared to 1 pill/day regimens, 2+ pills/day regimens were associated with a higher hazard of discontinuation (hazard ratio (HR) =3.44with 95% confidence interval (CI) = 1.25, 9.48).  Higher viral load and patients without insurance were also found to be significantly associated with higher hazards of discontinuation.  CONCLUSIONS: The 1 pill/day regimen in the initial HAART treatment was associated with a lower hazard of discontinuation than any other regimen used.