Highly active antiretroviral therapy (HAART) delays clinical progression to AIDS by suppressing viral replication, allowing the immune system to reconstitute. These virologic and immunologic consequences do not occur uniformly among HAART users; markers of HIV disease stage at the time of HAART initiation are critical determinants of the progression while under HAART. In this paper, we review studies describing the heterogeneous virologic and immunologic progression following the initiation of HAART, and update findings obtained in the Multicenter AIDS Cohort Study that show that CD4 cell count and history of antiretroviral therapy at the time of initiation are independent determinants of response.