PROJECT SUMMARY This proposal brings together leading experts on mental health and HIV service delivery from top US and Malawian institutions, including the Malawian Ministry of Health (MOH), to evaluate the effectiveness and cost-effectiveness of an evidence-based stepped model of depression care integrated into Malawi's national HIV platform. Malawi has the 9th highest HIV prevalence in the world, and the 2nd lowest GDP per capita. Additionally, depression is a leading cause of disability but remains untreated in over 90% of cases. Lack of cost-effective, scalable solutions is a fundamental barrier. Against this backdrop, one major success has been the scale-up of a network of 709 HIV clinics, with over half a million patients enrolled in ART. As a chronic care system with dedicated human resources and infrastructure, this presents a strategic platform for integrating depression care, and responds to a robust evidence base outlining the bi-directionality of depression and HIV outcomes. Members of the research team have already successfully piloted this model in a neighboring district, demonstrating feasibility, acceptability and preliminary efficacy. Moreover, the team has already integrated treatment for other non-communicable diseases such as hypertension and diabetes into the HIV care system of Neno District, Malawi. Additionally, team members have successfully integrated depression care into HIV services in similar settings (Uganda) and instituted depression care models such as Problem Solving Therapy (PST) in settings throughout sub-Saharan Africa, in addition to conducting formative work on depression prevalence, screening and diagnostic tools in Malawi. Building from this, we will evaluate a gold standard stepped model of depression care that combines group-based PST with antidepressant therapy (ADT) in n=420 patients with moderate/severe depression (PHQ-9>10), following a stepped wedge cluster randomized design in which 14 facilities are randomized to implement the model in five steps over a 15-month period. Primary outcomes (depression symptoms, functional impairment, and overall health) and secondary outcomes (e.g. HIV: viral load, ART adherence; diabetes: A1C levels; hypertension: systolic blood pressure) will be measured every three months, inclusive of baseline, pre-treatment, post-treatment (3 months), 6- and 12 months follow-up. We will also evaluate the model's suitability for national scale-up from three perspectives: cost-effectiveness, feasibility and research capacity. Cost-effectiveness will examine direct treatment effects on depressive symptoms, as well as indirect benefits on (a) comorbid conditions, and (b) burden of care among household members of participants. Feasibility will be assessed through key informant interviews with n=20 study participants and n=10 providers. Research capacity will be supported through (i) a university course and field placement instituted in Years 3-5, (ii) a local research mentorship program, and (iii) a training protocol on the depression care package, inclusive of evaluation tools, for national dissemination launched in Year 5.

PROJECT NARRATIVE To-date, depression interventions in low- and middle-income countries have struggled on two fronts: they often fail to leverage the infrastructure of existing chronic care systems to reduce costs and improve quality, and they tend to overlook indirect benefits on broader health outcomes and other individuals. We will evaluate the effectiveness and cost-effectiveness of a stepped-care model of depression treatment integrated into Malawi’s national HIV platform, specifically examining depression symptoms, functional impairment, and overall health of 420 adults with moderate/severe depression. We will achieve this by conducting a stepped-wedge cluster randomized trial in which n=14 health facilities are randomized to implement depression care for patients (n=420) in five steps (2-3 facilities per step) over a 15-month period and measured at three months intervals inclusive of baseline, pre-treatment, post-treatment, 6- and 12-months follow-up—with cost-effectiveness taking into account indirect benefits on comorbid conditions such as HIV and hypertension, and household- level effects such as reduced burden of care.