Depression affects 20-30% of people living with HIV/AIDS (PLWHA) in the U.S. and predicts greater sexual risk behaviors, lower antiretroviral (ARV) medication adherence, and worse clinical outcomes. Yet little experimental evidence addresses the critical clinical question of whether depression treatment improves ARV adherence and clinical outcomes in PLWHA with depression. The Strategies to Link Antidepressant and Antiretroviral Management at Duke, UAB, and UNC (SLAM DUNC) Study is a randomized clinical effectiveness trial funded by the National Institute for Mental Health. The objective of SLAM DUNC is to test whether a depression treatment program integrated into routine HIV clinical care affects ARV adherence. PLWHA with depression (n = 390) are randomized to enhanced usual care or a depression treatment model called Measurement-Based Care (MBC). MBC deploys a clinically supervised Depression Care Manager (DCM) to provide evidence-based antidepressant treatment recommendations to a non-psychiatric prescribing provider, guided by systematic and ongoing measures of depressive symptoms and side effects. MBC has limited time requirements and the DCM role can be effectively filled by a range of personnel given appropriate training and supervision, enhancing replicability. In SLAM DUNC, MBC is integrated into HIV care to support HIV providers in antidepressant prescription and management. The primary endpoint is ARV adherence measured by unannounced telephone-based pill counts at 6. months with follow-up to 12. months and secondary endpoints including viral load, health care utilization, and depressive severity. Important outcomes of this study will be evidence of the effectiveness of MBC in treating depression in PLWHA and improving HIV-related outcomes. © 2012 Elsevier Inc.