Abstract Predictors of successful virologic, immunologic, and clinical response with combined antiretroviral therapy (cART) containing a boosted protease inhibitor or a nonnucleoside reverse transcriptase inhibitor were analyzed among an antiretroviral naive (ARV-naive) urban cohort. Measures of success included virologic suppression [HIV-1 viral load (VL) <400 copies/ml], an increase in CD4(+) T cells from baseline of >100 cells/microl, and lack of development of an AIDS-defining illness at 24 and 48 weeks after cART initiation. Two hundred and eighty-seven ARV-naive patients were included in this cohort, of which 76.7% were male and 86.8% were nonwhite. At the time of cART initiation their median age was 39 years, the geometric mean CD4(+) count was 42 cells/microl, and the mean viral load was 5.3 log(10) copies/ml. At 48 weeks, 72% of patients achieved virologic suppression, with > or =90% adherence and high school graduation predicting viral undetectability at 48 weeks. Baseline VL < or =100,000 copies/ml and a CD4(+) cell count >100 cells/microl were associated with viral suppression at 24 weeks [OR (95% CI) = 3.55 (1.29-9.81) and 3.96 (1.19-13.15), respectively]; female gender was associated with a greater increase in CD4(+) cell counts [OR (95% CI) = 7.41 (2.48-22.1)]. CDC stage A1-C2 at baseline predicted lack of clinical progression at 48 weeks. The results of this analysis of an ARV-naive cohort comprised predominantly of indigent, minority patients suggest that men who did not have a high school education and who had advanced HIV infection are less likely to have therapeutic success after cART initiation.