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Introduction: Perinatal depression is common among women living with HIV, but depression care is limited in low-resource settings. We examined (1) characteristics of women receiving Problem Solving Therapy (PST) versus antidepressant therapy (ADT), (2) treatment response by modality, and (3) correlates of treatment response. Methods: This analysis used data from 191 Ugandan women in the intervention arm of a cluster randomized controlled trial of task-shifted, stepped-care depression treatment for pregnant women living with HIV (PWLWH). Treatment response was defined as scoring < 5 on the nine-item Patient Health Questionnaire (PHQ-9). Bivariate analysis and multivariable logistic regression were used to examine characteristics of women by treatment group and correlates of treatment response. Results: Of 134 participants with depression, 129 (96%) were treated: 84 (65%) received PST and 45 (35%) received ADT. Severe depression at treatment initiation was more common in those receiving ADT (28.9% versus 4.8%, Fischer's Exact Test < 0.001). Treatment response was higher for PST (70/84; 83.3%) than ADT (30/45; 66.7%; p =.03). ADT side effects were rare and minor; no infants had serious congenital defects. Of 22 participants (19%) who did not respond to treatment, only five received intensified management. Social support and interpersonal violence were associated with treatment response (adjusted odds ratio, [aOR] = 3.06, 95% CI = 1.08–8.66 and aOR = 0.64, 95% CI = 0.44–0.93). Discussion: Both depression treatment modalities yielded high response rates in Ugandan PWLWH; ADT was well-tolerated. Our results highlight a need to build capacity to implement the stepped-care protocol for non-responders and screen for social support and interpersonal violence. Significance: What is Already Known on this Subject?Prior research has demonstrated the feasibility and effectiveness of delivering collaborative care for depression in low-resource settings including Uganda. What this Study adds?Both Problem-Solving Therapy and antidepressant therapy yielded high treatment response rates among pregnant women living with HIV in Uganda who met criteria for depression, and antidepressant therapy was well tolerated. This study highlights a need to build capacity to implement the task-shifted stepped-care protocol for women whose depression does not respond to initial treatment, and to screen for social support and interpersonal violence. [ABSTRACT FROM AUTHOR]