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. In this proposal, we aim to develop an in vitro and in vivo system to examine the impact of cocaine on HIV infection.
In Specific Aim #1, we propose to examine the effects of cocaine on quiescent CD4 T cell (G0) permissiveness to HIV and the kinetics of infection. This will be assessed by comparing the HIV infection kinetics of G0 cells in the presence or absence of cocaine (in vivo and in vitro). The mechanisms of cocaine effects will be determined by the use of neutralizing antibodies and receptor agonists and antagonists.
In Specific Aim #2, we will investigate in vivo the effect of cocaine on HIV replication using the humanized BLT mouse model. These mice have a fully reconstituted human immune system that allows for the study of HIV infection. Mice will be infected with HIV prior or post-drug exposure and disease progression will be assessed compared to non-infected and/or untreated mice. In addition, we will examine the reactivation of viral reservoir from latently infected cells isolated from these mice. The proposed studies will expand our knowledge on HIV infection in quiescent cells in drug abusers, will shed light on the mechanisms which may activate provirus expression in this long-lived stable reservoir, and ultimately lead to the development of effective therapies tailored to individuals, both HIV seropositives and seronegatives, suffering from drug abuse.

Public Health Relevance

Drugs of abuse have been shown to promote immune dysfunction and influence human immunodeficiency virus (HIV) disease progression. Resting T cells make up the majority of the stable viral reservoir. In this proposal, which focuses on the effects of cocaine on HIV infection of quiescent T cells, the goals are to examine in vivo and in vitro how stimulants (1) affect HIV infectivity in quiescent T cells and (2) influence the activation of the HIV reservoir.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
NeuroAIDS and other End-Organ Diseases Study Section (NAED)
Program Officer
Purohit, Vishnudutt
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Internal Medicine/Medicine
Schools of Medicine
Los Angeles
United States
Zip Code
Saleh, Suha; Lu, Hao K; Evans, Vanessa et al. (2016) HIV integration and the establishment of latency in CCL19-treated resting CD4(+) T cells require activation of NF-κB. Retrovirology 13:49
Burke, Bryan P; Levin, Bernard R; Zhang, Jane et al. (2015) Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector. Mol Ther Nucleic Acids 4:e236
Nixon, Christopher C; Schwartz, Brandon H; Dixit, Dhaval et al. (2015) Cocaine exposure impairs multilineage hematopoiesis of human hematopoietic progenitor cells mediated by the sigma-1 receptor [corrected]. Sci Rep 5:8670
Kim, Sohn G; Lowe, Emily L; Dixit, Dhaval et al. (2015) Cocaine-mediated impact on HIV infection in humanized BLT mice. Sci Rep 5:10010
Kim, Sohn G; Jung, James B; Dixit, Dhaval et al. (2013) Cocaine exposure enhances permissiveness of quiescent T cells to HIV infection. J Leukoc Biol 94:835-43
Nixon, Christopher C; Vatakis, Dimitrios N; Reichelderfer, Scott N et al. (2013) HIV-1 infection of hematopoietic progenitor cells in vivo in humanized mice. Blood 122:2195-204
Zack, Jerome A; Kim, Sohn G; Vatakis, Dimitrios N (2013) HIV restriction in quiescent CD4⁺ T cells. Retrovirology 10:37