Regional variability in human immunodeficiency virus (HIV) care engagement remains underexplored. Multiple logistic models compared HIV outcomes for participants from 5 Southern (n = 557) and 6 non-Southern (n = 670) sites. Southern participants were less likely to experience viral suppression (adjusted odds ratio [aOR], 0.52; 95% confidence interval [CI],.37-.72) and had a higher likelihood of a CD4+ count <200 cells/μL (aOR, 1.53; 95% CI, 1.17-2.00). HIV intervention and social safety net programs should be expanded. Clinical Trials Registration NCT01612169.