Cocaine enhances HIV-1-induced CD4(+) T-cell apoptosis: implications in disease progression in cocaine-abusing HIV-1 patients.

Pandhare J, Addai AB, Mantri CK, Hager C, Smith RM, Barnett L, Villalta F, Kalams SA, Dash C
Am J Pathol. 2014 184 (4): 927-936

PMID: 24486327 · PMCID: PMC3970001 · DOI:10.1016/j.ajpath.2013.12.004

Substance abuse is a major barrier in eradication of the HIV epidemic because it serves as a powerful cofactor for viral transmission, disease progression, and AIDS-related mortality. Cocaine, one of the commonly abused drugs among HIV-1 patients, has been suggested to accelerate HIV disease progression. However, the underlying mechanism remains largely unknown. Therefore, we tested whether cocaine augments HIV-1-associated CD4(+) T-cell decline, a predictor of HIV disease progression. We examined apoptosis of resting CD4(+) T cells from HIV-1-negative and HIV-1-positive donors in our study, because decline of uninfected cells plays a major role in HIV-1 disease progression. Treatment of resting CD4(+) T cells with cocaine (up to 100 μmol/L concentrations) did not induce apoptosis, but 200 to 1000 μmol/L cocaine induced apoptosis in a dose-dependent manner. Notably, treatment of CD4(+) T cells isolated from healthy donors with both HIV-1 virions and cocaine significantly increased apoptosis compared with the apoptosis induced by cocaine or virions alone. Most important, our biochemical data suggest that cocaine induces CD4(+) T-cell apoptosis by increasing intracellular reactive oxygen species levels and inducing mitochondrial depolarization. Collectively, our results provide evidence of a synergy between cocaine and HIV-1 on CD4(+) T-cell apoptosis that may, in part, explain the accelerated disease observed in HIV-1-infected drug abusers.

Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

MeSH Terms (12)

Apoptosis CD4-Positive T-Lymphocytes Cell Separation Cocaine Cocaine-Related Disorders Disease Progression Dopamine Uptake Inhibitors Flow Cytometry HIV-1 HIV Infections Humans Virion

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