Services for prevention of mother-to-child-transmission (PMTCT) of HIV have been scaled up across Uganda, yet one in five new HIV cases still result from vertical transmission. This is in large part due to ~30% of HIV+ mothers not receiving PMTCT care; and of those who do, two-thirds do not adhere to the full PMTCT care continuum. Over 30% of HIV+ pregnant women are clinically depressed, and depression has harmful effects on adherence to the PMTCT care continuum, yet mental health care is absent in Ugandan antenatal care (ANC) clinics, leaving depression rarely diagnosed and treated. Research is needed to establish a viable model for treating depression in the context of PMTCT care, and to understand how depression treatment may mitigate the harmful effects of depression on PMTCT adherence so that optimal pregnancy outcomes can be achieved. While there is some evidence that depression treatment and depression alleviation improve adherence to general HIV care processes, such benefits have not been evaluated in the more complex PMTCT care continuum, which includes not only maternal ART use (both pre- and post-natal), but also child use of ART prophylaxis, periodic child HIV testing, and uniform breast feeding. Building on our prior research in integrating task-shifted depression care into HIV clinics in Uganda, and our use of problem solving therapy (PST) and antidepressant therapy (ADT) for treating depression in low resource settings, administered by trained lay persons and nurses, respectively, this application proposes a cluster RCT to compare the effects of an evidence-based depression care model vs. usual care on adherence to each step of the PMTCT care continuum at 8 ANC clinics in Uganda. Usual care in Ugandan ANC clinics includes referrals to psychiatric specialists in district hospitals, as well as the Ministry of Health’s Family Support Group (FSG) program for HIV+ women, which provides psychosocial support through group education to help women adhere to PMTCT care and manage their pregnancy. At the 4 experimental sites we will add to usual care the gold standard, stepped care approach to providing evidence-based depression treatment consisting of PST (via individual counseling, and content integrated into specific FSG group sessions) or ADT (for women with severe or refractory depression, or who refuse PST). At each site, 50 HIV+ pregnant women (n=400) who screen positive for potential depression will enroll and be followed until 18-months post-delivery. Primary outcomes consist of maternal viral suppression and adherence to each step of the PMTCT care continuum. We will evaluate the incremental cost-effectiveness of integrating evidence-based depression care, relative to usual care. If efficacious and cost-effective, this study will provide a model for integrating depression care into ANC clinics and promoting optimal adherence to the PMTCT care continuum and maternal and child health outcomes.