PROJECT SUMMARY Women who use drugs (WWUD), specifically heroin, shoulder a disproportionate burden of the HIV epidemic in Tanzania. Despite advances in HIV prevention biomedical interventions, including pre-exposure prophylaxis (PrEP), PrEP uptake has been slow in Tanzania. Mental disorders, including depression, anxiety, and post- traumatic stress disorder, are high among WWUD and are known barriers to HIV prevention behaviors, including PrEP engagement. Inattention to the high prevalence of mental health problems in WWUD, is likely to undermine efforts to increase the use of HIV prevention strategies, including PrEP, among this highly vulnerable, yet understudied population. Motivational interviewing (MI) and cognitive-behavioral therapy (CBT) are evidence-based interventions that have been successfully delivered by paraprofessionals, both globally and in Tanzania, for a range of health conditions, including substance use disorders and mental disorders, and to improve uptake and adherence of HIV prevention strategies. The Common Elements Treatment Approach (CETA) is a transdiagnostic, CBT-based intervention developed for use in low- and middle-income countries for delivery by lay counselors with no or limited previous mental health training. The goal of this study is to adapt MI for PrEP engagement (MI-PrEP) and a combined CETA and MI-PrEP interventions (CETA+MI-PrEP) for delivery by paraprofessionals in Dar es Salaam, Tanzania, to optimize PrEP engagement among WWUD. The specific aims of this study are to: (1) identify barriers and motivators to PrEP engagement, and the types of paraprofessionals who could most effectively deliver the MI-PrEP and CETA+MI- PrEP interventions using in-depth interviews and focus groups with WWUD, peer- and non-peer community health workers, lay counselors, and mental health specialists, (2) systematically adapt MI-PrEP and CETA for WWUD with co-occurring mental disorders in Tanzania using the ADAPT-ITT model, and (3) assess the feasibility, fidelity, and preliminary efficacy of the MI-PrEP and CETA+MI-PrEP interventions in a three-arm pilot feasibility trial with 120 WWUD with co-occurring symptoms of mental disorders. A combination of interviews, structured surveys, and supervision will be used to assess for intervention feasibility and fidelity. The preliminary efficacy of the intervention will be estimated for the primary outcomes of PrEP engagement and secondary outcomes of opioid use, symptoms of depressive, anxiety, and post-traumatic stress, and PrEP motivation and barriers. This pilot feasibility study will: (1) advance our understanding of the unique factors that contribute to the PrEP engagement among WWUD, (2) address the HIV prevention needs of an understudied, yet extremely high-risk population, and (3) result in culturally appropriate and locally adapted MI-PrEP and CETA+MI-PrEP interventions that can be formally tested in a Hybrid Type I Effectiveness- Implementation randomized controlled trial.