Benzoylecgonine, a Major Cocaine Metabolite, Enhances HIV‐1 Integration and Replication in Immune Cells

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Several studies have indicated an association between drug abuse and an increased risk for HIV/AIDS. The presence of benzoylecgonine (BE), a major cocaine by‐product, is almost a certain indication that a person has consumed the drug. Therefore, BE testing in urine is commoner than testing of cocaine itself in Drug Screening Tests. It has been demonstrated that cocaine influences HIV‐1 replication in peripheral blood mononuclear cells (PBMCs), CD4+T cells, and humanized mice. However, the effects of cocaine and its metabolite on HIV‐1 replication have not been elucidated. The goal of this study is to examine the effects of BE and cocaine on HIV‐1 integration in immune cells that serve as the primary targets HIV in vivo. PBMCs and CD4+ T cells were isolated from human blood by Ficoll‐based reagents. HIV‐1 integration and replication were measured by quantitative nested PCR and flow cytometry. We demonstrate that BE and cocaine increase HIV‐1 integration in immune cells in a dose dependent manner. A direct role of cocaine on HIV‐1 integration was further confirmed by in vitro integration assay using HIV‐1 pre‐integration complexes (PICs) isolated from infected cells treated with cocaine. We observed a maximum increase in integration at 50uM. We also demonstrate that cocaine can localize to the nucleus of CD4+ T cells by utilizing ESI based mass spectrometry. Given that cocaine abuse serves as a powerful cofactor for HIV‐1 infection, replication, and pathogenesis in vivo, our data may have implications in the worsening of disease among cocaine abusing HIV patients.
*Amma Addai is supported by T32 grant #5T32HL007735‐19 from NIH/NHLBI to Dr. S. E. Adunyah. The research is in part supported by grants DA024558, DA30896, DA033892 and DA021471 from NIDA/NIH to CD.