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
References
Arnsten JH, Demas PA, Grant RW, Gourevitch MN, Farzadegan H et al (2002) Impact of active drug use on antiretroviral therapy adherence and viral suppression in HIV-infected drug users. J Gen Intern Med 17:377–381
Cachay ER, Moini N, Kosakovsky Pond SL, Pesano R, Lie YS et al (2007) Active methamphetamine use is associated with transmitted drug resistance to non-nucleoside reverse transcriptase inhibitors in individuals with HIV infection of unknown duration. Open AIDS J 1:5–10
Carrico AW, Johnson MO, Moskowitz JT, Neilands TB, Morin SF et al (2007) Affect regulation, stimulant use, and viral load among HIV-positive persons on anti-retroviral therapy. Psychosom Med 69:785–792
Carrico AW, Johnson MO, Colfax GN, Moskowitz JT (2010) Affective correlates of stimulant use and adherence to anti-retroviral therapy among HIV-positive methamphetamine users. AIDS Behav 14:769–777
CDC (2012) HIV Surveillance Report,. http://www.cdc.gov/hiv/topics/surveillance/resources/22
Chaturvedi S, Frame P, Newman SL (1995) Macrophages from human immunodeficiency virus-positive persons are defective in host defense against Histoplasma capsulatum. J Infect Dis 171:320–327
Cisneros IE, Ghorpade A (2012) HIV-1, methamphetamine and astrocyte glutamate regulation: combined excitotoxic implications for neuro-AIDS. Curr HIV Res 10:392–406
Colfax G, Shoptaw S (2005) The methamphetamine epidemic: implications for HIV prevention and treatment. Curr HIV/AIDS Rep 2:194–199
Colfax G, Coates TJ, Husnik MJ, Huang Y, Buchbinder S et al (2005) Longitudinal patterns of methamphetamine, popper (amyl nitrite), and cocaine use and high-risk sexual behavior among a cohort of San Francisco men who have sex with men. J Urban Health 82:i62–70
Drumright LN, Little SJ, Strathdee SA, Slymen DJ, Araneta MR et al (2006) Unprotected anal intercourse and substance use among men who have sex with men with recent HIV infection. J Acquir Immune Defic Syndr 43:344–350
Eissenberg LG, Goldman WE, Schlesinger PH (1993) Histoplasma capsulatum modulates the acidification of phagolysosomes. J Exp Med 177:1605–1611
Ellis RJ, Childers ME, Cherner M, Lazzaretto D, Letendre S et al (2003) Increased human immunodeficiency virus loads in active methamphetamine users are explained by reduced effectiveness of antiretroviral therapy. J Infect Dis 188:1820–1826
Everall I, Salaria S, Roberts E, Corbeil J, Sasik R et al (2005) Methamphetamine stimulates interferon inducible genes in HIV infected brain. J Neuroimmunol 170:158–171
Fairbairn N, Kerr T, Milloy MJ, Zhang R, Montaner J et al (2011) Crystal methamphetamine injection predicts slower HIV RNA suppression among injection drug users. Addict Behav 36:762–763
Friedman H, Pross S, Klein TW (2006) Addictive drugs and their relationship with infectious diseases. FEMS Immunol Med Microbiol 47:330–342
Gaskill PJ, Calderon TM, Coley JS, Berman JW (2013) Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND. J Neuroimmune Pharmacol 8:621–642
Gavrilin MA, Mathes LE, Podell M (2002) Methamphetamine enhances cell-associated feline immunodeficiency virus replication in astrocytes. J Neurovirol 8:240–249
Gruenewald PJ, Johnson FW, Ponicki WR, Remer LG, Lascala EA (2010) Assessing correlates of the growth and extent of methamphetamine abuse and dependence in California. Subst Use Misuse 45:1948–1970
Halkitis PN, Parsons JT, Stirratt MJ (2001) A double epidemic: crystal methamphetamine drug use in relation to HIV transmission among gay men. J Homosex 41:17–35
Harms R, Morsey B, Boyer CW, Fox HS, Sarvetnick N (2012) Methamphetamine administration targets multiple immune subsets and induces phenotypic alterations suggestive of immunosuppression. PLoS One 7:e49897
Hinkin CH, Barclay TR, Castellon SA, Levine AJ, Durvasula RS et al (2007) Drug use and medication adherence among HIV-1 infected individuals. AIDS Behav 11:185–194
http://www.who.int/mediacentre/factsheets/fs360/en/index.html
Hurt CB, Torrone E, Green K, Foust E, Leone P et al (2010) Methamphetamine use among newly diagnosed HIV-positive young men in North Carolina, United States, from 2000 to 2005. PLoS One 5:e11314
In SW, Son EW, Rhee DK, Pyo S (2004) Modulation of murine macrophage function by methamphetamine. J Toxicol Environ Health A 67:1923–1937
King WD, Larkins S, Hucks-Ortiz C, Wang PC, Gorbach PM et al (2009) Factors associated with HIV viral load in a respondent driven sample in Los Angeles. AIDS Behav 13:145–153
Kipp AM, Desruisseau AJ, Qian HZ (2011) Non-injection drug use and HIV disease progression in the era of combination antiretroviral therapy. J Subst Abuse Treat 40:386–396
Lane HC (2010) Pathogenesis of HIV infection: total CD4+ T-cell pool, immune activation, and inflammation. Top HIV Med 18:2–6
Liang H, Wang X, Chen H, Song L, Ye L et al (2008) Methamphetamine enhances HIV infection of macrophages. Am J Pathol 172:1617–1624
Loftis JM, Choi D, Hoffman W, Huckans MS (2011) Methamphetamine causes persistent immune dysregulation: a cross-species, translational report. Neurotox Res 20:59–68
Mahajan SD, Hu Z, Reynolds JL, Aalinkeel R, Schwartz SA et al (2006) Methamphetamine modulates gene expression patterns in monocyte derived mature dendritic cells: implications for HIV-1 pathogenesis. Mol Diagn Ther 10:257–269
Mansergh G, Shouse RL, Marks G, Guzman R, Rader M et al (2006) Methamphetamine and sildenafil (Viagra) use are linked to unprotected receptive and insertive anal sex, respectively, in a sample of men who have sex with men. Sex Transm Infect 82:131–134
Mantri CK, Mantri JV, Pandhare J, Dash C (2014) Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV-1 miRNA expression. Am J Pathol 184:92–100
Marcondes MC, Flynn C, Watry DD, Zandonatti M, Fox HS (2010) Methamphetamine increases brain viral load and activates natural killer cells in simian immunodeficiency virus-infected monkeys. Am J Pathol 177:355–361
Markowitz M, Mohri H, Mehandru S, Shet A, Berry L et al (2005) Infection with multidrug resistant, dual-tropic HIV-1 and rapid progression to AIDS: a case report. Lancet 365:1031–1038
Marquez C, Mitchell SJ, Hare CB, John M, Klausner JD (2009) Methamphetamine use, sexual activity, patient-provider communication, and medication adherence among HIV-infected patients in care, San Francisco 2004–2006. AIDS Care 21:575–582
Martinez LR, Mihu MR, Gacser A, Santambrogio L, Nosanchuk JD (2009) Methamphetamine enhances histoplasmosis by immunosuppression of the host. J Infect Dis 200:131–141
Misawa F, Shimizu K, Fujii Y, Miyata R, Koshiishi F et al (2011) Is antipsychotic polypharmacy associated with metabolic syndrome even after adjustment for lifestyle effects?: a cross-sectional study. BMC Psychiatry 11:118
Nair MP, Saiyed ZM (2011) Effect of methamphetamine on expression of HIV coreceptors and CC-chemokines by dendritic cells. Life Sci 88:987–994
Nair MP, Samikkannu T (2012) Differential regulation of neurotoxin in HIV clades: role of cocaine and methamphetamine. Curr HIV Res 10:429–434
Nair MP, Mahajan S, Sykes D, Bapardekar MV, Reynolds JL (2006) Methamphetamine modulates DC-SIGN expression by mature dendritic cells. J Neuroimmune Pharmacol 1:296–304
Nair MP, Saiyed ZM, Nair N, Gandhi NH, Rodriguez JW et al (2009) Methamphetamine enhances HIV-1 infectivity in monocyte derived dendritic cells. J Neuroimmune Pharmacol 4:129–139
Newman SL (1999) Macrophages in host defense against Histoplasma capsulatum. Trends Microbiol 7:67–71
Parsons JT, Kowalczyk WJ, Botsko M, Tomassilli J, Golub SA (2013) Aggregate versus day level association between methamphetamine use and HIV medication non-adherence among gay and bisexual men. AIDS Behav 17:1478–1487
Patterson TL, Semple SJ, Staines H, Lozada R, Orozovich P et al (2008) Prevalence and correlates of HIV infection among female sex workers in 2 Mexico-US border cities. J Infect Dis 197:728–732
Peck JA, Reback CJ, Yang X, Rotheram-Fuller E, Shoptaw S (2005) Sustained reductions in drug use and depression symptoms from treatment for drug abuse in methamphetamine-dependent gay and bisexual men. J Urban Health 82:i100–108
Pelchen-Matthews A, Kramer B, Marsh M (2003) Infectious HIV-1 assembles in late endosomes in primary macrophages. J Cell Biol 162:443–455
Plankey MW, Ostrow DG, Stall R, Cox C, Li X et al (2007) The relationship between methamphetamine and popper use and risk of HIV seroconversion in the multicenter AIDS cohort study. J Acquir Immune Defic Syndr 45:85–92
Potula R, Persidsky Y (2008) Adding fuel to the fire: methamphetamine enhances HIV infection. Am J Pathol 172:1467–1470
Qian HZ, McGowan CC, Mitchell VJ, Cassell H, Perez G, et al (2011) Non-injection substance abuse, depression, and adherence to antiretroviral therapy among HIV-infected patients. Rome, Italy
Rawson RA, Anglin MD, Ling W (2002) Will the methamphetamine problem go away? J Addict Dis 21:5–19
Reback CJ, Larkins S, Shoptaw S (2003) Methamphetamine abuse as a barrier to HIV medication adherence among gay and bisexual men. AIDS Care 15:775–785
Reiner BC, Keblesh JP, Xiong H (2009) Methamphetamine abuse, HIV infection, and neurotoxicity. Int J Physiol Pathophysiol Pharmacol 1:162–179
Semple SJ, Patterson TL, Grant I (2002) Motivations associated with methamphetamine use among HIV+ men who have sex with men. J Subst Abuse Treat 22:149–156
Shoptaw S, Reback CJ (2006) Associations between methamphetamine use and HIV among men who have sex with men: a model for guiding public policy. J Urban Health 83:1151–1157
Shoptaw S, Stall R, Bordon J, Kao U, Cox C et al (2012) Cumulative exposure to stimulants and immune function outcomes among HIV-positive and HIV-negative men in the multicenter AIDS cohort study. Int J STD AIDS 23:576–580
Sun J, Soos T, Kewalramani VN, Osiecki K, Zheng JH et al (2006) CD4-specific transgenic expression of human cyclin T1 markedly increases human immunodeficiency virus type 1 (HIV-1) production by CD4+ T lymphocytes and myeloid cells in mice transgenic for a provirus encoding a monocyte-tropic HIV-1 isolate. J Virol 80:1850–1862
Talloczy Z, Martinez J, Joset D, Ray Y, Gacser A et al (2008) Methamphetamine inhibits antigen processing, presentation, and phagocytosis. PLoS Pathog 4:e28
Thiede H, Valleroy LA, MacKellar DA, Celentano DD, Ford WL et al (2003) Regional patterns and correlates of substance use among young men who have sex with men in 7 US urban areas. Am J Public Health 93:1915–1921
Toussi SS, Joseph A, Zheng JH, Dutta M, Santambrogio L et al (2009) Short communication: methamphetamine treatment increases in vitro and in vivo HIV replication. AIDS Res Hum Retroviruses 25:1117–1121
Walensky RP, Paltiel AD, Losina E, Mercincavage LM, Schackman BR et al (2006) The survival benefits of AIDS treatment in the United States. J Infect Dis 194:11–19
Wang X, Ho WZ (2011) Drugs of abuse and HIV infection/replication: implications for mother-fetus transmission. Life Sci 88:972–979
Wires ES, Alvarez D, Dobrowolski C, Wang Y, Morales M et al (2012) Methamphetamine activates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and induces human immunodeficiency virus (HIV) transcription in human microglial cells. J Neurovirol 18:400–410
Wohl AR, Johnson DF, Lu S, Jordan W, Beall G et al (2002) HIV risk behaviors among African American men in Los Angeles county who self-identify as heterosexual. J Acquir Immune Defic Syndr 31:354–360
Yu Q, Zhang D, Walston M, Zhang J, Liu Y et al (2002) Chronic methamphetamine exposure alters immune function in normal and retrovirus-infected mice. Int Immunopharmacol 2:951–962
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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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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DOI: https://doi.org/10.1007/s11481-015-9604-2