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The Complex Interaction Between Methamphetamine Abuse and HIV-1 Pathogenesis

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Abstract

The global HIV/AIDS pandemic has claimed the lives of an estimated 35 million people. A significant barrier for combating this global pandemic is substance use since it is associated with HIV transmission, delayed diagnosis/initiation of therapy, and poor adherence to therapy. Clinical studies also suggest a link between substance use and HIV-disease progression/AIDS-associated mortality. Methamphetamine (METH) use is one of the fastest-growing substance use problems in the world. METH use enhances high-risk sexual behaviors, therefore increases the likelihood of HIV-1 acquisition. METH use is also associated with higher viral loads, immune dysfunction, and antiretroviral resistance. Moreover, METH use has also been correlated with rapid progression to AIDS. However, direct effects of METH on HIV-1 disease progression remains poorly understood because use of METH and other illicit drugs is often associated with reduced/non adherence to ART. Nevertheless, in vitro studies demonstrate that METH increases HIV-1 replication in cell cultures and animal models. Thus, it has been proposed that METH’s potentiating effects on HIV-1 replication may in part contribute to the worsening of HIV-1 pathogenesis. However, our recent data demonstrate that METH at physiologically relevant concentrations has no effect and at higher concentrations inhibits HIV-1 replication in CD4+ T cells. Thus, the goal of this review is to systematically examine the published literature to better understand the complex interaction between METH abuse and HIV-1 disease progression.

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Abbreviations

HIV:

human immunodeficiency virus

AIDS:

acquired immunodeficiency syndrome

ART:

antiretroviral therapy

METH:

methamphetamine

MSM:

men who have sex with men

STIs:

sexually transmitted infections

SIV:

simian immunodeficiency virus

RNA:

ribonucleic acid

CXCR4:

chemokine (C-X-C motif) receptor 4

CCR5:

C-C chemokine receptor type 5

ERK2:

extracellular-regulated kinase

MAPK:

mitogen-activated protein kinase

MDM:

monocyte derived macrophage

INF- α:

interferon-alpha

STAT1:

signal transducer and activator of transcription-1

FIV:

feline immunodeficiency virus

CNS:

central nervous system

LTR:

Long terminal repeats

DC-SIGN:

dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin

MIP-1:

macrophage inflammatory protein 1

RANTES:

regulated on activation T cell expressed and secreted

VSV-G:

vesicular stomatitis virus g protein

miRNA:

microRNA

IL-2:

interlukin 2

IFN-γ:

interferon-gamma

TNF-α:

tumor necrosis factor alpha

NO:

nitric oxide

IL-1β:

interlukin beta

IL-8:

interlukin 8

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Acknowledgments

Grant numbers and sources of support: This work is partly supported by grants DA024558, DA30896, DA033892 and the DIDARP grant R24DA021471 from NIDA/NIH to CD. We also acknowledge the RCMI Grant G12MD007586, the Vanderbilt CTSA grant UL1RR024975, the Meharry Translational Research Center (MeTRC) CTSA grant (U54 RR026140 from NCRR/NIH, the U54 grant MD007593 from NIMHD/NIH and the DA029506 grant that established the patient samples.

Ethical Statement

The authors declare that the manuscript has not been submitted to more than one journal for simultaneous consideration. No data have been fabricated or manipulated (including images) to support your conclusions.

Author Contributions

RC and HQ carried out search of clinical literatures. JP and CD carried literature survey of cellular and molecular studies. CD designed and directed the entire study. All authors contributed to write and review the manuscript.

Competing Interests

The authors declare no competing financial and non-financial interests.

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Correspondence to Han-Zhu Qian or Chandravanu Dash.

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Passaro, R.C., Pandhare, J., Qian, HZ. et al. The Complex Interaction Between Methamphetamine Abuse and HIV-1 Pathogenesis. J Neuroimmune Pharmacol 10, 477–486 (2015). https://doi.org/10.1007/s11481-015-9604-2

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