Project Summary Recent HIV outbreaks among rural people who inject drugs (PWID) highlighted significant gaps in HIV prevention science. HIV risk behaviors among PWID are influenced by several factors, including access to sterile injection equipment and pre-exposure prophylaxis (PrEP), law enforcement practices, and utilization of medications for opioid use disorder (MOUD) and harm reduction (e.g., accessing syringe services programs [SSPs]). None of the existing HIV prevention literature has examined the relationships between complex patterns of interactions and engagements among a triad of HIV risk modifiers (MOUD, harm reduction, and law enforcement), high-risk behaviors, and HIV incidence among rural PWID during periods of peak HIV transmission. Social network characteristics are another driver of HIV transmission as PWID networks may be characterized as having specific norms surrounding injection practices and risk reduction strategies. Studying how combinations of factors known to influence HIV risks interact at the individual- and network-levels among PWID in rural communities with HIV outbreaks presents a unique opportunity to inform the design of interventions that can respond to rapidly evolving HIV prevention needs and barriers. Evidence generated from urban studies documents that network-oriented interventions focused on social influence processes are able to shift norms related to high-risk sexual behaviors and injection practices and use of risk reduction strategies, leading to reductions in HIV risk behaviors and HIV transmission. However, there is limited literature describing how to adapt network-oriented HIV prevention interventions for rural PWID. To address these gaps, our study aims: 1. To examine longitudinal changes in the associations between the frequency and types of engagements with a triad of HIV risk modifiers (i.e., MOUD, harm reduction, and law enforcement), HIV risk behaviors, and HIV incidence among a cohort of rural PWID (N=400) during a HIV outbreak over 18 months; 2.To examine how the associations between egocentric network characteristics (e.g., perceived norms, turnover, density) and utilization of three evidence-based approaches to HIV risk reduction (MOUD, PrEP, and SSPs) change over 18 months among a cohort of rural PWID during a HIV outbreak; 3. To engage rural PWID in the adaptation and pilot testing of a network-oriented intervention to reduce high-risk injection practices and sexual behaviors; and 3A. To conduct a pilot randomized controlled trial (RCT) of the adapted intervention among rural PWID (N=60) to assess acceptability and feasibility. The proposed research is directly responsive to the 2022-2026 NIDA Strategic Plan. Aims 1 and 2 map directly to Goal 2.2, “Accelerate the science of harm reduction.” Additionally, this study aligns with Priority Scientific Area #3: Accelerate Research on the Intersection of Substance Use and HIV in that our rural study setting is experiencing a HIV outbreak drive...