Network-based study design, statistical, and modeling solutions for HIV among populations that use illicit substances: Informing interventions and policy in real-world settings using existing data - Project Summary/Abstract Young black men who have sex with men (BMSM) experience a disproportionate burden of HIV infection despite advances in HIV treatment and prevention, and their HIV risk often involves illicit substance use. These individuals are frequently part of sexual networks with HIV transmission risk. HIV interventions have the potential for substantial impact beyond the treated individual. This is known as spillover (i.e., interference), and occurs when one participant's exposure affects another's health outcome. Although spillover has been evaluated for therapies like vaccines, there is preliminary evidence that HIV interventions result in meaningful spillover, such as treatment as prevention and pre- exposure prophylaxis (PrEP). However, there have been limited evaluations of spillover in this marginalized population. Important methodological work remains in the context of studies to evaluate the spillover of HIV interventions among populations that use illicit substances. The objective of this application is to evaluate the spillover of HIV interventions among marginalized populations using both secondary data analyses of existing data and simulation approaches. This project will provide new insights about spillover in the following network studies in Chicago, Illinois: uConnect, PrEP Chicago, and Neighborhood and Networks Cohort Study. The development of sample size and power formulas to evaluate spillover in sociometric network-based studies will facilitate post hoc evaluations of power in the motivating studies. This will also allow investigators to conduct adequately powered future studies of spillover to determine the most effective HIV interventions among young BMSM. Network dependence and missing data in network-based studies are common and largely unaddressed in the assessment of spillover. We will develop causal methods addressing both these threats to valid inference. We will conduct a pre-deployment evaluation of spillover for HIV interventions, including a PrEP peer change intervention and PrEP delivery focused on substance- using agents in a calibrated agent-based network model of young BMSM in Chicago, Illinois. We have assembled a transdisciplinary, expert team of leading methodologists, modelers, substance use clinicians, and HIV prevention scientists, who also hold key leadership roles in the three motivating network studies and agent-based network model. Resources at the University of Rhode Island will provide a centrally-located environment to facilitate research, including collaborative opportunities with leading HIV and substance use researchers. This project will advance modeling and statistical methodology for HIV prevention among marginalized populations to assess spillover and contribute important substantive studies of spillover in both secondary data analysis and agent-based modeling, providing novel insights to advance HIV prevention and treatment among young BMSM.