Abstract PrEP is a powerful and potentially groundbreaking HIV prevention strategy, but its public health impact will depend on widescale adoption by persons at greatest risk for contracting HIV infection. PrEP awareness and use remain especially low among African American MSM in mid-sized cities across the center of the country, and very little research has tested interventions that can increase PrEP awareness, benefit perception, and normative support—and decrease PrEP stigma and concerns—among African American MSM in these cities. PrEP can achieve its full public health potential only when its uptake among racial minority MSM in neglected mid-sized American cities is increased. In prior research, our team established that network-level interventions can reach and be used to deliver effective HIV risk reduction interventions to Black MSM in the industrial Midwest, including hard-to-reach men hidden in the community. The planned mixed- methods research will now evaluate a network intervention to increase PrEP uptake among high-risk African American MSM in Milwaukee and Cleveland, cities where HIV racial disparities are profound but PrEP use is low. In a formative research phase, in-depth interviews will be conducted with African American MSM, PrEP providers, and other key informants in each city to identify understandings, concerns, barriers, and facilitators of PrEP use. In the main intervention trial phase, 36 social networks of high-risk racial minority MSM (expected n=504 participants) will be enrolled, 18 networks per city, by recruiting high-risk initial “seeds,” members of each seed's MSM friendship network, and then two outward successive rings of their friends. All study participants will receive baseline counseling for PrEP and risk reduction. The 36 networks will then be randomized in equal numbers to intervention and comparison conditions. In each intervention condition network, a cadre of network leaders open to PrEP, trusted for advice, and highly interconnected with others will attend an intervention that educates and then provides training and guidance in diffusing messages to friends to encourage PrEP uptake, correcting PrEP misconceptions and stigma, and instilling positive PrEP norms and benefit perceptions. At baseline and 6- and 15-month followup points, participants will complete measures of PrEP use corroborated by the testing of dried blood spot specimens for tenofovir; measures of PrEP related knowledge, attitudes, perceived norms, and stage of change readiness; sexual risk practices; and substance use. We hypothesize that the network intervention will produce greater PrEP adoption by HIV- participants than that found in comparison networks. PrEP knowledge, attitudes, intentions, peer norms, and stage of change readiness will be explored as both mediators and as secondary outcomes. Intervention effects on HIV incidence will be mathematically modeled to determine its public health impact. This research will test a novel ...