Depression is an exceedingly common comorbidity among HIV-infected patients. Depression has been associated with a range of adverse health behaviors and outcomes including reduced antiretroviral (ARV) medication adherence, increased HIV transmission risk behaviors, increased virologic failure, and higher mortality. Antidepressant medications and psychotherapy are effective in treating depression in HIV-infected patients. Consequently, an important question for HIV clinicians, researchers, and policy-makers is the extent to which depression treatment can improve HIV behavioral, risk transmission, and clinical outcomes and help realize the full potential of ARV treatment-as-prevention. Limited real-world, robust evidence exists about the population-level impact on transmission and health that could be achieved by investing in high-quality depression treatment for HIV patients. Precise and valid causal estimates of the effect of depression treatment on HIV outcomes, especially from large and generalizable samples, are necessary to define the HIV-related return on such investment. A small number of randomized controlled trials have demonstrated improvements in ARV adherence after intensive psychotherapy-based depression treatment interventions, but have been conducted in small and non-generalizable samples. Several observational studies have suggested a positive association of antidepressant treatment with ARV adherence, but these studies have generally not used appropriate causal inference statistical methods to account for the dynamic relationship between depressive symptoms and treatment. Studies to date have also generally grouped all antidepressant treatment together, rather than distinguish adequate (best-practices) treatment from clinical inertia - the tendency of non-psychiatric providers to fail to titrate antidepressant doses to address ongoing symptoms. In this project, we will draw on the rich information in the large and diverse CNICS observational cohort, encompassing 25,000 patients from 8 CFAR clinical sites across the US, to complete the following aims: (1) to characterize the frequency of adequate vs. inadequate antidepressant treatment provided within HIV clinical care;(2) to estimate the magnitude of the effect of antidepressant treatment, and specifically adequate antidepressant treatment, on HIV-related behavioral and health outcomes using state-of-the-art causal inference methods;and (3) to assess whether the effect of adequate depression treatment on HIV outcomes differs for certain subgroups, such as those with greater depressive severity, concurrent anxiety, or problematic alcohol or drug use. This scope of work is significant because we will (1) define the current "depression treatment gap" in HIV primary care, (2) define the population-level impact on HIV outcomes achievable by reducing that gap, and (3) define subpopulations for which the reduction of the treatment gap could be most beneficial. Our proposal is innovative in its use of advanced causal inference methods and its focus on distinguishing adequate from inadequate antidepressant treatment. The large and diverse patient population represented in CNICS will enhance the generalizability of this work's findings to the population of HIV-infected patients engaged in HIV primary care across the United States.
In this project, we will start by defining the magnitude of the depression treatment gap, or opportunity for improvement in depression treatment, in current HIV primary care. In particular, we will characterize the frequency of adequate (e.g., best-practices) vs. inadequate antidepressant treatment provided in HIV clinical care. We will then estimate the effect of antidepressant treatment, and especially adequate antidepressant treatment, on HIV-related behaviors and health outcomes (e.g., medication adherence and mortality) among HIV-infected patients with depression. Finally, we will examine whether the benefits of antidepressant treatment are larger or smaller in specific subgroups, such as those with concurrent alcohol and drug use. This work will characterize the potential HIV- related benefits to be gained by improving the extent and quality of depression treatment for HIV- infected patients in the US.