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2015 DEPARTMENT OF MEDICINE RESEARCH DAY Title of Poster: Cocaine Modulation of Quiescent T Cells Enhances HIV Infection Presenter: Dimitrios Vatakis Division: Hematology-Oncology ☒Faculty ☐Fellow ☐Resident ☐Post-doc Research Fellow ☐Graduate Student ☐Medical Student ☐Other Principal Investigator/Mentor: Dimitrios Vatakis Co-Investigators: Thematic Poster Category: Infections, Injury and Repair, Inflammation, Host Defense, Immunology, Hemostasis and Atherosclerosis Abstract Stimulant use such as cocaine has been shown to impact the human immune system. In regards to the human immunodeficiency virus (HIV) infection, a number of studies have indicated that cocaine users are at an increased risk for infection and display more rapid disease progression and morbidity. However due to many variables such as adherence to antiretroviral therapy, use of multiple classes of drugs and co-infections among others, it is difficult to fully appreciate the impact drug abuse has on HIV disease. We hypothesize that cocaine will influence the kinetics of HIV infection in quiescent cells by increasing their permissiveness to infection. To this end, quiescent cells were exposed to cocaine for three days. Based on our data, 3-day exposure, when compared to quiescent cells, resulted in increased reverse transcription kinetics, higher levels of viral cDNA, increased viral RNA and protein synthesis. In addition, the 3-day treated cells progressed to the G1b phase of the cell cycle and displayed a marked increase in the levels of CCR5. The cocaine effects were mediated via the Dopamine D4 and SIGMA-1 receptor pathways. The patterns of enhanced HIV infection were also observed in vivo using BLT humanized mice. Acute cocaine exposure of mice resulted in increased inflammation, accelerated kinetics of infection and higher viral loads. Thus, cocaine has a potentiating effect of HIV replication through increased permissiveness of resting T cells and increased immune activation.