OBJECTIVE HIV infection has a devastating impact on individual and public health, and affects populations disproportionately. Treatment with antiretroviral therapy (ART) saves lives, but long-term adherence to ART is critical to its success. We performed an observational cohort study to determine the influence of race, sex and other sociodemographic factors on early ART discontinuations among HIV-infected persons. METHODS TennCare-enrolled adults of black or white non-Hispanic race beginning ART with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) between 1996-2003 (N=3654) were assessed for early discontinuation. A subgroup of discontinuations was validated using the primary medical record. RESULTS Blacks were more likely than whites to discontinue NNRTIs (37 vs. 28%; P=0.003) and PIs (36 vs. 25%; P < or = 0.001). In multivariable models adjusting for race, sex, age, early HIV-related medical encounter, urban residence and TennCare enrollment category, black race, female sex and younger age were independent predictors of discontinuation among those starting PIs. Among persons starting NNRTIs, black race, younger age and a disability-based enrollment category predicted early drug discontinuation, but female sex did not. CONCLUSIONS Our results suggest that sociodemographic factors were associated with early NNRTI and PI discontinuation in this population, and some factors were ART class specific.