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Cocaine Increased Viral Load & Decreased CD4s in Mice
  Cocaine Enhances Human Immunodeficiency Virus Replication in a Model of Severe Combined Immunodeficient Mice Implanted with Human Peripheral Blood Leukocytes
Michael D. Roth,1 Donald P. Tashkin,1 Ruth Choi,2 Beth D. Jamieson,2 Jerome A. Zack,2 and Gayle Cocita Baldwin2
Divisions of 1Pulmonary and Critical Care Medicine and 2Hematology-Oncology, Department of Medicine, University of California, Los Angeles, School of Medicine, Los Angeles
This study found cocaine increased viral load & viral replication and decreased CD4 counts in mice. The study is one of many that for years have suggested cocaine use may accelerate HIV. While the evidence is not clear certainly this should serve as a warning to people using cocaine that this presents risks to accelerate HIV.
ABSTRACT: Epidemiologic studies have identified cocaine as a cofactor for development of acquired immunodeficiency syndrome (AIDS). To evaluate this interaction, human peripheral blood leukocytes (PBL) were implanted into severe combined immunodeficient mice and infected with human immunodeficiency virus (HIV) in both the presence and absence of cocaine. Concurrent administration of cocaine resulted in significantly more PBL becoming infected with HIV in vivo (38.85% vs. 18.5%). The number of CD4+ cells recovered from HIV-infected, cocaine-treated animals was significantly lower than that from mice infected with HIV in the absence of cocaine (6.5 ? 104 vs. 19 ? 104) and was associated with a lower CD4 : CD8 ratio and a dramatic increase in virus load. We noted a 200- to 300-fold increase in HIV RNA copy numbers in the peripheral blood obtained from cocaine-treated, HIV-infected animals when compared with HIV-infected controlsExposure to cocaine alone did not affect the implantation of PBL, suggesting a specific interaction between cocaine and HIV. This report describes a model for evaluating HIV cofactors and supports cocaine's role in the development and progression of AIDS.
A variety of cofactors may increase the risk for or progression of clinical disease associated with human immunodeficiency virus (HIV). There is strong circumstantial evidence that exposure to drugs of abuse, specifically cocaine, fall into this category. By multiple logistic regression analysis, 3084 persons attending a sexually transmitted disease clinic were studied for associations between HIV infectivity and individual subject characteristics. Of the 1911 subjects who denied having high-risk behaviors (male homosexuality, intravenous drug use, or sexual contact with high-risk persons), crack cocaine and HIV infection were associated with an odds ratio of 10.6 : 1 for women and 3.3 : 1 for men. This relationship is supported by other epidemiologic studies and by reports suggesting that cocaine depresses the immune system both in vivo and in vitro. Epidemiologic studies have linked cocaine to the progression of AIDS and to the risk for opportunistic infections. If cocaine mediates clinically significant effects on host defense, the link between cocaine abuse and progression of AIDS could be related to an increased risk for secondary opportunistic infections. Alternatively, since cocaine modulates the distribution and activation of target lymphocytes, modifies cytokine production, and alters cell trafficking of immune cells, cocaine might affect HIV infectivity and/or replication by these means. In vitro studies show these results. Finally, and perhaps most significant, study results show that cocaine facilitates the replication of HIV in human peripheral blood leukocytes (PBL) in vitro.
Although compelling, the link between cocaine use and HIV is based largely on indirect evidence, and the exact mechanisms responsible for this link have not been clearly delineated. To more directly evaluate the interaction between cocaine and HIV in vivo, we adapted a hybrid human-murine model (huPBL-SCID mouse). This approach was initially developed by Mosier et al. as a relevant animal model for in vivo assessment of HIV pathogenesis. Our goal was to determine whether systemic exposure of huPBL-SCID mice to cocaine would affect HIV burden and/or the number and distribution of T cell subsets in vivo.
AUTHOR'S CONCLUSIONS: Although both in vitro analyses and epidemiologic studies suggest that cocaine increases susceptibility to HIV, our data provide direct evidence that cocaine can enhance HIV replication in vivo. In vitro studies are constrained by their inability to account for complex interactions that occur in vivo, such as the effects of cocaine on the hypothalamic-pituitary-adrenal axis, on neurotransmitter release, or on the production of chemokines and cytokines by other cell populations. Our findings confirm existing indirect evidence and provide a significant connection between cocaine exposure in vivo and the progression of HIV.
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