We evaluated 1422 antiretroviral therapy (ART)-naive patients infected with human immunodeficiency virus (HIV) who initiated highly active antiretroviral therapy between 1 August 1 1996 and 31 July 2000 and were monitored until 31 March 2002. Patients were stratified on the basis of baseline levels of HIV RNA (<50,000, 50,000-99,999, and > or =100,000 copies/mL). Cox regression was used to determine independent predictors of time to death. After adjustment for adherence to ART and other potential confounders, baseline levels of HIV RNA of > or =100,000 copies/mL remained independently associated with mortality (adjusted relative hazard, 1.71; 95% confidence interval, 1.08-2.70; P=.023). If appropriately confirmed, these findings have important implications for the development of therapeutic guidelines.