© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. The effect of depressive symptoms on progression through the human immunodeficiency virus (HIV) treatment cascade is poorly characterized. Methods. We included participants from the Centers for AIDS Research Network of Integrated Clinic Systems cohort who were antiretroviral therapy (ART) naive, had at least 1 viral load and HIV appointment measure after ART initiation, and a depressive symptom measure within 6 months of ART initiation. Recent depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) and categorized using a validated cut point (PHQ-9 =10). We followed participants from ART initiation through the first of the following events: loss to follow-up (12 months with no HIV appointment), death, administrative censoring (2011-2014), or 5 years of follow-up. We used log binomial models with generalized estimating equations to estimate associations between recent depressive symptoms and having a detectable viral load (=75 copies/mL) or missing an HIV visit over time. Results. We included 1057 HIV-infected adults who contributed 2424 person-years. At ART initiation, 30% of participants reported depressive symptoms. In multivariable analysis, recent depressive symptoms increased the risk of having a detectable viral load (risk ratio [RR], 1.28; 95% confidence interval [CI], 1.07, 1.53) over time. The association between depressive symptoms and missing an HIV visit (RR, 1.20; 95% CI, 1.05, 1.36) moved to the null after adjustment for preexisting mental health conditions (RR, 1.00; 95% CI, 0.85, 1.18). Conclusions. Recent depressive symptoms are a risk factor for unsuppressed viral load, while preexisting mental health conditions may influence HIV appointment adherence.