Although routine clinical markers are used routinely to determine the stage of human immunodeficiency virus (HIV) disease, their use in monitoring response to antiretroviral therapy is poorly defined. Selected clinical markers were evaluated for their ability to predict first-line antiretroviral therapy success. No clinically meaningful variables were identified that predicted virologic or immunological success, implying that the CD4+ cell count and HIV type 1 RNA level data are required for optimal management of antiretroviral therapy. © 2006 by the Infectious Diseases Society of America. All rights reserved.