Dr. Lesko's applied research interests are primarily related to describing and improving clinical outcomes for persons with HIV living in the United States. She has a particular focus on (1) estimating the prevalence and effects of mental health disorders, alcohol misuse, substance use, and alcohol and other substance use disorders; and (2) monitoring and improving progress through the HIV care continuum, and better defining and describing "engagement in HIV care" for predicting clinical outcomes. Dr. Lesko also works on the application and development of epidemiologic methods and theory for estimating policy- and patient-relevant health effects from observational data. Specifically, she has published on causal inference theory and application (how can we determine that changing something about A will lead to a change in Y?); external validity and quantitative approaches to generalizing data from one sample to other target populations (if an intervention worked in one group of people, what will the effect of that intervention in another group of people?); and analyzing time-to-event data in the presence of censoring (e.g., loss to follow-up) or competing events.