Impact of tobacco smoke in HIV progression: a major risk factor for the development of NeuroAIDS and associated CNS disorders
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The advent of highly active antiretroviral therapy (HAART) and combined antiretroviral therapy (cART) has substantially increased the life expectancy of patients infected with human immunodeficiency virus (HIV). However, this has brought into sharp contrast the incidence of several non-acquired immunodeficiency syndrome (non-AIDS) diseases such as NeuroAIDS, which identifies a group of neurological disorders caused primarily by HIV-mediated damage to the central and peripheral nervous systems. Given the patients’ depleted immune condition, the use and abuse of drug and addictive substances such as tobacco smoking can further deteriorate their overall health and accelerate the progression and severity of the disease. In this review, we detail the pathogenesis, progression, and characteristics of HIV, and the impact of tobacco smoking as a risk factor for the progression of the disease to NeuroAIDS. This is a poorly understood aspect of HIV-related complications that needs to be addressed.
Subjects and methods
Review of theoretical approaches and knowledge synthesis.
Tobacco smoking is highly prevalent in HIV patients when compared to the general population. The oxidative damage and inflammatory stress caused by chronic smoking on the cerebrovascular system have been well established. Considering that HIV patients have an impaired immune system and smokers per se are more susceptible to viral and bacterial inflammatory neuropathologies than non-smokers, it is conceivable that tobacco smoking is a risk factor for the progression of HIV into NeuroAIDS and related neurological impairments.
Tobacco smoke (TS) may bring about a synergistic effect in the context of persistent inflammatory state and cerebrovascular damage which facilitate HIV infection and progression to NeuroAIDS when compared to non-smokers.
KeywordsBlood–brain barrier Oxidative stress Inflammation Smoking Brain disorders Abuse Cognitive
Acquired immunodeficiency syndrome
Activator protein 1
Large conductance, Ca2 + --activated K+ Channels
High FOS-like antigen 1
High FOS-like antigen 2
Central nervous system
Acquired immunodeficiency syndrome
Human immunodeficiency virus
Highly active antiretroviral therapy
Combined antiretroviral therapy
AIDS dementia complex
HIV-associated cognitive–motor complex
HIV-associated neurocognitive disorders
Reactive oxygen species
Protein tyrosine kinases
Transforming growth factor type 1
This work was supported by the National Institutes of Health/ National Institute on Drug Abuse 2R01-DA029121-01A1 to Dr. Luca Cucullo.
A.B. prepared the draft of the manuscript, figure preparations. L.C. conceived the study, assisted with data interpretation, drafting of the manuscript, and preparation of the figures. L.C. also oversaw the research study and provided funding. Both authors reviewed the manuscript.
Compliance with ethical standards
The authors declare no competing interests.
This article does not contain any studies with human participants or animals performed by the author.
- Abbruscato TJ, Lopez SP, Mark KS, Hawkins BT, Davis TP (2002) Nicotine and cotinine modulate cerebral microvascular permeability and protein expression of ZO-1 through nicotinic acetylcholine receptors expressed on brain endothelial cells. J Pharm Sci 91:2525–2538. https://doi.org/10.1002/jps.10256 CrossRefGoogle Scholar
- Ambrose JA, Barua RS (2004) The pathophysiology of cigarette smoking and cardiovascular disease: an update. JACC 43(10):1731–1737. https://doi.org/10.1016/j.jacc.2003.12.047
- Atluri VSR (2016) Editorial: HIV and illicit drugs of abuse. Front Microbiol 7:221. https://doi.org/10.3389/fmicb.2016.00221
- Centers for Disease Control and Prevention (2018) About HIV/AIDS, pp.2–3Google Scholar
- Circu ML, Aw TY (2010) Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med 48:749–762. https://doi.org/10.1016/j.freeradbiomed.2009.12.022 CrossRefGoogle Scholar
- Cole SB, Langkamp-Henken B, Bender BS, Findley K, Herrlinger-Garcia KA, Uphold CR (2005) Oxidative stress and antioxidant capacity in smoking and nonsmoking men with HIV/acquired immunodeficiency syndrome. Nutr Clin Pract 20:662–667. https://doi.org/10.1177/0115426505020006662 CrossRefGoogle Scholar
- Conley LJ, Bush TJ, Buchbinder SP, Penley KA, Judson FN, Holmberg SD (1996) The association between cigarette smoking and selected HIV-related medical conditions. AIDS 10:1121–1126Google Scholar
- Earla R, Ande A, McArthur C, Kumar A, Kumar S (2014) Enhanced nicotine metabolism in HIV-1-positive smokers compared with HIV-negative smokers: simultaneous determination of nicotine and its four metabolites in their plasma using a simple and sensitive electrospray ionization liquid chromatography–tandem mass spectrometry technique. Drug Metab Dispos 42:282–293. https://doi.org/10.1124/dmd.113.055186 CrossRefGoogle Scholar
- Elzi L et al (2006) A smoking cessation programme in HIV-infected individuals: a pilot study. Antivir Ther 11:787–795Google Scholar
- Hasnis E, Bar-Shai M, Burbea Z, Reznick AZ (2007) Mechanisms underlying cigarette smoke-induced NF-kappaB activation in human lymphocytes: the role of reactive nitrogen species. J Physiol Pharmacol 58(Suppl 5):275–287Google Scholar
- Hawkins BT, Abbruscato TJ, Egleton RD, Brown RC, Huber JD, Campos CR, Davis TP (2004) Nicotine increases in vivo blood–brain barrier permeability and alters cerebral microvascular tight junction protein distribution. Brain Res 1027:48–58. https://doi.org/10.1016/j.brainres.2004.08.043 CrossRefGoogle Scholar
- Hossain M, Mazzone P, Tierney W, Cucullo L (2011) In vitro assessment of tobacco smoke toxicity at the BBB: do antioxidant supplements have a protective role?. BMC Neurosci 12:92. https://doi.org/10.1186/1471-2202-12-92
- Jin M et al (2012) A LC-MS/MS method for concurrent determination of nicotine metabolites and role of CYP2A6 in nicotine metabolism in U937 macrophages: implications in oxidative stress in HIV + smokers. J NeuroImmune Pharmacol 7:289–299. https://doi.org/10.1007/s11481-011-9283-6 CrossRefGoogle Scholar
- Kaisar MA, Sivandzade F, Bhalerao A, Cucullo L (2018) Conventional and electronic cigarettes dysregulate the expression of iron transporters and detoxifying enzymes at the brain vascular endothelium: in vivo evidence of a gender-specific cellular response to chronic cigarette smoke exposure. Neurosci Lett 682:1–9. https://doi.org/10.1016/j.neulet.2018.05.045 CrossRefGoogle Scholar
- Kalra R, Singh SP, Savage SM, Finch GL, Sopori ML (2000) Effects of cigarette smoke on immune response: chronic exposure to cigarette smoke impairs antigen-mediated signaling in T cells and depletes IP3-sensitive ca(2+) stores. J Pharmacol Exp Ther 293:166–171Google Scholar
- Lane HC (2010) Pathogenesis of HIV infection: total CD4+ T-cell pool, immune activation, and inflammation. Top HIV Med 18:2–6Google Scholar
- Lopez S et al (2004) Mitochondrial effects of antiretroviral therapies in asymptomatic patients. Antivir Ther 9:47–55Google Scholar
- Mazzone P, Tierney W, Hossain M, Puvenna V, Janigro D, Cucullo L (2010) Pathophysiological impact of cigarette smoke exposure on the cerebrovascular system with a focus on the blood–brain barrier: expanding the awareness of smoking toxicity in an underappreciated area. Int J Environ Res Public Health 7(12):4111–4126. https://doi.org/10.3390/ijerph7124111 CrossRefGoogle Scholar
- Naik P, Sajja RK, Prasad S, Cucullo L (2015) Effect of full flavor and denicotinized cigarettes exposure on the brain microvascular endothelium: a microarray-based gene expression study using a human immortalized BBB endothelial cell line. BMC Neurosci 16:38. https://doi.org/10.1186/s12868-015-0173-3 CrossRefGoogle Scholar
- National Institute on Drug Abuse (2012) How does drug abuse affect the HIV epidemic?Google Scholar
- Peluffo G, Calcerrada P, Piacenza L, Pizzano N, Radi R (2009) Superoxide-mediated inactivation of nitric oxide and peroxynitrite formation by TS in vascular endothelium: studies in cultured cells and smokers. Am J Physiol Heart Circ Physiol 296:H1781–H1792. https://doi.org/10.1152/ajpheart.00930.2008 CrossRefGoogle Scholar
- Prasad S, Cucullo L (2015) Impact of tobacco smoking and type-2 diabetes mellitus on public health: a cerebrovascular perspective. J Pharmacovigil (Suppl 2) pii: e003. https://doi.org/10.4172/2329-6887.S2-e003
- Sharp PM, Hahn BH (2011) Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med 1(1):a006841. https://doi.org/10.1101/cshperspect.a006841
- UNAIDS (2017) Fact sheet — Latest global and regional statistics on the status of the AIDS epidemic.Google Scholar
- U.S. Department of Veterans Affairs (2018) AIDS-defining illnessesGoogle Scholar
- Zeinolabediny Y et al (2017) HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders. Sci Rep 7. https://doi.org/10.1038/s41598-017-10875-0
- Zhang YL, Ouyang YB, Liu LG, Chen DX (2015) Blood–brain barrier and neuro-AIDS. Eur Rev Med Pharmacol Sci 19:4927–4939Google Scholar