PROJECT SUMMARY/ABSTRACT This K23 Career Development Award will provide early career support for the investigation of behavioral and biological risk factors for HIV/STI transmission caused by methamphetamine (MA) use among men who have sex with men (MSM). This K23 award will provide support for the candidate to develop expertise in the following areas: 1) Biological impacts of MA use and addiction medicine; 2) Clinical trials methods and biobehavioral interventions; 3) Applied immunology; 4) Professional development; and 5) Responsible conduct of research. Dr. Blair will be mentored by a multidisciplinary team with expertise in addiction, infectious diseases, immunology, and statistics. Dr. Steven Shoptaw has an extensive track record in addiction research and training of future independent investigators. Dr. Jesse Clark will provide mentorship in clinical trial methods, operations, and safety procedures; Dr. Grace Aldrovandi will provide mentorship in applied immunology, with an emphasis on mucosal immunology; and Dr. Robert Weiss will provide mentoring in advanced statistical methods. MA use is an important driver of HIV transmission and the burgeoning STI epidemic among MSM. Understanding the interaction of biological and behavioral risk factors for HIV/STI transmission caused by MA use is imperative for effective HIV/STI interventions. Dr. Blair proposes to investigate the joint effects of MA use, HIV, sexual risk behavior, and rectal gonorrhea/chlamydia (GC/CT) on systemic and rectal inflammation. Stored plasma specimens and behavioral data obtained every 6 months over 2 years from 140 MSM will be used to assess the joint effects of HIV and MA use on systemic inflammation and risk behavior using a 2x2 factorial design stratified by HIV serostatus (70 positive; 70 negative) and results of urine MA screening (70 with MA use; 70 without MA use). 40 HIV-negative MA-using MSM (20 with rectal GC/CT; 20 without rectal GC/CT) will be recruited separately from a community-based university research clinic. MA exposure will be manipulated using contingency management (CM) to evaluate the effects of a decline in MA use on biological markers of inflammation (e.g., cytokines). Following initiation of CM, sexual risk behaviors will be assessed weekly for 8 weeks. Inflammatory rectal cytokines will be measured weekly with rectal swabs and linked with biomarkers of MA exposure over 8 weeks. These activities will accomplish the following aims: 1) Measure the joint effects of HIV and MA use on systemic cytokine concentrations and risk behavior; 2) Identify the effects of MA exposure and concomitant rectal GC/CT on rectal cytokine concentrations; and 3) Evaluate the association of MA use frequency with sexual risk behavior in the setting of rectal inflammation. Through this K23 Career Development Award, Dr. Blair will establish herself as an independent clinician-investigator with expertise in intersectional research on the biological and behavioral impacts of ...