This application is being submitted to PA-18-591 in accordance with NOT-TW-19-003. Barriers to accessing evidence-based treatments for depression, such as treatment complexity, mean that people living with HIV (PLWH) rarely receive depression therapies in community settings. To address unmet mental health needs within this group, the parent grant is implementing a scalable stepped-care intervention for depression and adherence to antiretroviral therapy in viraemic people living with HIV in Zimbabwe, through a 2-arm parallel group randomized clinical trial. The active intervention, called TENDAI includes brief motivational and problem-solving therapy, and is being compared with Enhanced Usual Care. Primary outcome at 12 months is proportion of HIV viral suppression in each condition. Secondary outcome is depression assessed at 4, 8 and 12 months using the PHQ-9. The Ministry of Health in Zimbabwe, who are partners in the parent trial, and NGOs in the region, would like to implement the TENDAI intervention more widely. However, in low-resource settings it will be critical to rationalise implementation of interventions in line with evidence. A barrier we will face to wider implementation is lack of knowledge as to who will benefit most. Research is urgently needed on tools which might guide the implementation of cost-effective depression care. The NIMH-pioneered RDoC initiative presents a biologically valid framework for understanding the cognitive and affective disruptions that characterize major depression and the role of brain systems in these disruptions. In the US, RDoC metrics of cognitive control and negative valence, have been found to aid in streamlining and matching treatments for depression to those who will benefit most. Ultimately, such research is hoped to provide brain heath solutions to guide the implementation of cost-effective depression care. However there has been virtually no research on predictors of depression treatment response in low and middle income countries (LMICs) or in PLWH. In this supplemental application, we propose to integrate the NIMH Research Domain Criteria (RDoC) initiative into the TENDAI trial by incorporating RDoC metrics of cognitive and affective function with strong links to major depression. This will allow us to determine baseline associations between cognitive control, negative valence, and standard measures of depression in PLWH, as well as determine whether RDoC metrics predict depression treatment response in PLWH. This research will be a vital first step in gathering proof of concept that the RDoC framework can contribute to guiding implementation of scalable stepped care neuro-health interventions in a low-income country context in PLWH. Our work links directly to the NIMH priority to use data already being collected to model and test causal relations among interventions, intervention targets, and proximal and clinical outcomes.

Narrative Improving the implementation of evidence-based treatments for depression in community settings for people living with HIV (PLWH) is a priority to enhance quality of life and to increase the likelihood of adherence to antiretroviral therapy and viral suppression. Our parent grant is implementing a scalable stepped-care treatment for depression and non-adherence to HIV medication for depressed PLWH, in HIV clinics in Zimbabwe. We propose to integrate RDoC neuropsychological tools for cognitive control and negative valence into our parent trial, and to examine how these constructs relate to depression and predict treatment outcomes, with considerable potential to inform neuro-health implementation in a LMIC context.