The purpose of this study was to evaluate predictors of HIV-1 disease progression in a cohort of predominantly female and minority adolescents who had acquired their HIV-1 infections through sexual risk behaviors. Subjects were identified from the REACH cohort who were not on antiretroviral therapy for at least 1 year and whose baseline CD4⁺ T cells were >300 cells/mm³. Biomedical and demographic characteristics of the subjects at the start of the study period were evaluated as predictors of CD4⁺ T cell loss in univariate and multivariate models. Two-thirds of the 99 subjects meeting the selection criteria were female and 87% were black or Hispanic similar to the REACH cohort as a whole. Higher absolute CD8⁺ CD38⁺ T cell counts at the start of the assessment period were associated with a greater rate of loss of CD4⁺ T cells. HIV-1 RNA viral load was among other potential predictors of HIV-1 disease progression that had no association with the rate of CD4⁺ T cell loss in this cohort. This study extends the observed association of higher CD8⁺ CD38⁺ T cells numbers being predictive of HIV-1 disease progression into predominantly female, minority youth.