Cocaine Enhances HIV-1–Induced CD4+ T-Cell Apoptosis

Abstract

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.

Cocaine exposure impairs multilineage hematopoiesis of human hematopoietic progenitor cells mediated by the sigma-1 receptor

“…Cocaine exposure is known to influence the function of immune cells. Cocaine can increase T-cell apoptosis, alter immune related miRNA profiles, change immune activation state, and impair lymphocyte proliferation 13 14 15 16 17 . However, little has been studied in terms of how drugs of abuse impact hematopoiesis.…”

Drug Use is Associated with Anti-CD4 IgG-mediated CD4+ T Cell Death and Poor CD4+ T Cell Recovery in Viral-suppressive HIV-infected Individuals Under Antiretroviral Therapy

“…Nonetheless, results in animal in vivo and in human in vitro suggest that illicit drugs (e.g., cocaine, marijuana, opiates) affect HIV viral replication [54-56]. In addition, high dose (200-1000 mg/L) cocaine has been shown to induce CD4+ T cell apoptosis in vitro [57], suggesting that drug may directly impair immune function and contribute to loss of virologic control. In the current study, we found that drug is independently associated with CD4+ T cell reconstitution in treated HIV disease.…”

Cocaine-Mediated Autophagy in Astrocytes Involves Sigma 1 Receptor, PI3K, mTOR, Atg5/7, Beclin-1 and Induces Type II Programed Cell Death

“…A recent meta-analysis study involving 46 studies showed that cocaine abuse predominantly affects attention, impulsivity, verbal learning/memory, and working memory [7]. The mechanism by which cocaine causes cellular damage is complex, and has been associated with ER stress [8,9], apoptosis [10,11] and oxidative stress [12,13]. However, the exact mechanism of cocaine-induced neurotoxicity remains an area of interest.…”