PROJECT SUMMARY/ABSTRACT Stigma is a pervasive barrier to preventing HIV among persons who inject drugs (PWID). Kyrgyzstan is part of the world’s most rapidly expanding HIV epidemic in the Eastern Europe and Central Asia (EECA) region, where HIV is predominantly concentrated among PWID. Our previous work with PWID in Kyrgyzstan found experiences of HIV, drug use, and drug treatment (i.e. methadone) stigmas were associated with greater HIV risk behavior and low use of evidence-based HIV services, including syringe service programs (SSP) and methadone to treat opioid use disorder (MMT), which limited, timely HIV diagnoses. Following the launch of pre-exposure prophylaxis (PrEP) services in Kyrgyzstan, PrEP awareness increased among PWID with limited uptake but was not associated with stigma suggesting integrating PrEP referrals in stigma reduction programming may increase PWIDs engagement in PrEP and other evidence-based HIV services. Yet there is little to no evidence base on the potential effectiveness and implementation needs of evidence-based stigma reduction strategies that address HIV-related intersectional stigma at multiple levels with PWID in the EECA region. In line with NIDA and OAR priorities, the long-term goal is to rapidly advance evidence-based stigma mitigation efforts among PWID to improve HIV service uptake and turn the tide on the rapidly expanding EECA HIV epidemic. To achieve this goal, the current study will use the ADAPT-ITT model to adapt and refine effective community-level and health facility-level HIV stigma reduction strategies to intervene on intersecting drug use, MMT, and HIV stigma in the local context among PWID and MMT clinic staff (AIM 1). We will pilot the resulting multilevel stigma reduction intervention – LIFT – using a randomized waitlist control trial study design to evaluate the preliminary effectiveness of the LIFT intervention on stigma reduction and MMT/PrEP use (AIM 2) among 68 PWID and all staff from two MMT clinics. In parallel, a sequential mixed methods design will evaluate LIFT implementation outcomes and needs among our local implementation partners and 25 key stakeholders (AIM 3) to develop implementation strategies that can accelerate the pace and scale up of EECA stigma reduction efforts. To reduce risk of contamination via injection and treatment networks, we will conduct all community- and health facility-level intervention and waitlist control activities in distinct geographic districts in the capital city of Bishkek. This R34 pilot is the first EECA study to evaluate intersectional stigma mitigation efforts among PWID to reduce HIV transmission risk. This R34 is significant because stigma remains a fundamental driver of HIV transmission globally. This R34 pilot is highly innovative because it extends the current state of HIV stigma intervention research by integrating strategies that target intersecting stigmas at multiple levels to improve the impact of evidence-based HIV services and adv...