To address these barriers interventions are needed

To address these barriers, interventions are needed that impact macro-level structural factors, such as reducing poverty and income inequality, increasing educational attainment, and fostering more equitable gender norms. As seen by the Tucker et al. review, social determinants of health matter, and efforts to address them could improve outcomes across the continuum. Secondly, more interventions are needed to increase the availability, accessibility, and affordability of care. Many of these types of interventions were included in the Tucker et al. review and involve activities such as decentralization of care and task-shifting. However, more research is needed, especially on interventions that address multiple points on the continuum as opposed to those focusing on one specific component. For example, home-based HIV testing may improve testing uptake and initial EPZ004777 to care, but does it affect adherence and retention? What complementary interventions could be implemented simultaneously to improve all aspects of the continuum? Thirdly, changes to the management of HIV care could greatly improve outcomes across the continuum. More specifically, now that HIV is considered a chronic disease, () it could be integrated into a streamlined approach to care that addresses all chronic conditions concurrently, including mental health and non-communicable diseases. Additionally, it is vital that programs and research studies measure these barriers to account for potential mediation, which could help explain why some interventions succeed while others fail. Having robust, coordinated data collection at all points in the care continuum and across transitions from one stage to another are needed. As other researchers have noted, data from HIV care programs is often disjointed and focused on discrete outputs, such as number of people who engage in care, as opposed to tracking patients throughout the continuum (). Obtaining more information on people who are “lost to follow-up” would also help understand how these barriers affect peoples\' decisions to leave care and what motivates people to re-engage.
Major depressive disorder (MDD) is the single greatest cause of disability and frequently emerges during adolescence, which can lead to devastating social, personal, and medical consequences (). It is critical to understand how departure from typical brain development patterns impacts the incidence of depression, as it allows us to develop more effective treatments and better clinical interventions to prevent recurrent, chronic episodes. It is currently unclear how and why MDD frequently emerges during adolescence. Different theories including dual-process models have been reviewed to explain certain aspects of adolescent depressive disorders (). In dual-process models, the so-called hot and cold neural systems that underlie both typical and atypical human behavior are proposed. The bottom-up hot systems are represented by emotional processing arising from lower brain regions, passing upward through the limbic system and emerging as reactive or reflexive behaviors (). The top-down cold systems underlie cognitive processes arising from frontal and prefrontal brain regions, passing down towards the limbic system and emerging as proactive or reflective behaviors. Previous studies suggest that exaggerated neurodevelopmental imbalances between hot and cold systems contribute to the incidence of affective disorders in adolescence (). Evidence from imaging studies suggests altered functional connectivity in adults with MDD, such as increased physiological activity in regions of hot emotional processing and reduced activity in regions of cold cognitive control (). However, it remains unclear whether similar dysfunction is present in adolescents with MDD due to the limited number of studies and small sample sizes of the studies conducted. Pathophysiology of MDD in adolescents can be different than in adults, due to maturation changes in the adolescent brain ().