PROJECT ABSTRACT People living with HIV (PLWH) are 28 times more likely to be diagnosed with anal cancer than the general population. The Human Papillomavirus (HPV) is associated with >90% of anal cancers, and is also a significant cause of cervical, vaginal, penile, and oral cancers seen in this population. The HPV vaccine is an effective and safe approach to prevent and reduce the risk of HPV-related disease among PLWH. However, HPV vaccination remains low in PLWH despite formal recommendations from the CDC’s Advisory Committee on Immunization Practices to vaccinate immunocompromised individuals up to age 26 years with the 3-dose series-- and recently FDA approved to vaccinate up to age 45 years. The PI’s K01 serves as the rationale for this study. The PI found significant delays in follow up care after an abnormal anal Pap test. Delays in follow up after an anal Pap test in the absence of national guidelines to support screening in PLWH means the incidence of anal cancer will continue to rise among PLWH, especially as this population ages. Therefore, promotion of the HPV vaccine in this population as primary cancer prevention is a public health priority. However, the PI’s work found significant gaps in knowledge and awareness of the HPV vaccine as well as low uptake of the HPV vaccine (13.5%) in our population of rural PLWH. These findings support the next logical step to reduce cancer disparities as well as further the PI’s career trajectory through promotion of HPV vaccination among PLWH as part of a successful cancer prevention plan. However, HPV vaccine programs tailored and implemented in the HIV population is lagging for this high-risk group. The CDC’s 4 PillarsTM Transformation Program is a multi-level, evidence-based intervention that has been successfully utilized to increase HPV vaccination in the general population and is primed to be tested in the high-risk HIV population, particularly PLWH in the rural South. Guided by the RE-AIM framework, we will implement this project in three HIV clinics in Georgia and enroll n=365 PLWH who are age 18-45 years from those clinics. Aim 1) Tailor and refine the 4 PillarsTM program for implementation in rural and urban HIV clinics in Georgia; Aim 2) Test the effectiveness of the 4 PillarsTM program as measured by an increase in uptake rate in initiation of the HPV vaccine (primary endpoint) and vaccine completion (secondary endpoint) compared to historical baseline vaccination rate (control) among PLWH; Aim 2.1) Identify mediators and potential moderators of the intervention effects on HPV vaccination; Aim 3) Assess the sustainability of the intervention in vaccine uptake post-intervention; Aim 3.1) Assess scalability of the program for wider implementation via a future national RCT. As an Early-Stage Investigator, the PI (Wells) has assembled an outstanding research team that brings complementary expertise to successfully execute the aims of this research proposal. The proposed study is a novel a...