Because both renal disease and immune activation predict progression to acquired immunodeficiency syndrome (AIDS), we evaluated the associations between proteinuria>or=1+, as determined by dipstick analysis (7 [7%] of 1012 subjects); creatinine clearance of <90 mL/min (195 [18%] of 1071 subjects); and percentages of peripheral activated CD8 cells (CD8+CD38+HLA-DR+ cells) in antiretroviral-naive, human immunodeficiency virus (HIV)-infected subjects who were enrolled in AIDS Clinical Trials Group studies 384 and A5095. Proteinuria, but not creatinine clearance, was associated with higher percentages of CD8+CD38+HLA-DR+ cells (55% vs. 50%; P=.01), with even more pronounced differences noted among men and among blacks and Hispanics. Proteinuria may be a surrogate measurement of greater immune activation in HIV-infected patients initiating antiretroviral therapy.