Abstract
Neurocognitive disorders associated with human immunodeficiency virus (HIV) infected
individuals increase the risk of mortality and morbidity that remain a prevalent clinical complication
even in the antiretroviral therapy era. It is estimated that a considerable number of people in the HIV
community are developing neurological complications at their early stages of infection. The daily lives
of people with chronic HIV infections are greatly affected by cognitive declines such as loss of attention,
learning, and executive functions, and other adverse conditions like neuronal injury and dementia.
It has been found that the entry of HIV into the brain and subsequently crossing the blood-brain
barrier (BBB) causes brain cell damage, which is the prerequisite for the development of neurocognitive
disorders. Besides the HIV replication in the central nervous system and the adverse effects of antiretroviral
therapy on the BBB, a range of opportunistic infections, including viral, bacterial, and parasitic
agents, augment the neurological complications in people living with HIV (PLHIV). Given the
immuno-compromised state of PLHIV, these co-infections can present a wide range of clinical syndromes
with atypical manifestations that pose challenges in diagnosis and clinical management, representing
a substantial burden for the public health system. Therefore, the present review narrates the
neurological complications triggered by HIV and their diagnosis and treatment options. Moreover, coinfections
that are known to cause neurological disorders in HIV infected individuals are highlighted.
Keywords:
Human immunodeficiency virus, antiretroviral therapy, HIV associated neurological disorder, central nervous system, co-infections, blood-brain barrier.
Graphical Abstract
[10]
Abuse S. Office of the Surgeon General (US. Early intervention, treatment, and management of substance use disorders. In: Facing Addiction in America: The Surgeon General's Report on Alcohol, Drugs, and Health. US Department of Health and Human Services 2016.
[29]
Coffin JM, Hughes SH, Varmus HE. Retroviruses.The Place of Retroviruses in Biology. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press 1997.
[55]
Louboutin JP, Strayer DS. Blood-brain barrier abnormalities caused by HIV-1 gp120: Mechanistic and therapeutic implications. Scientific World J 2012; 2012: 482575.
[65]
Daliparty VM, Balasubramanya R. HIV Encephalitis. StatPearls 2021.
[67]
Eggleton JS, Nagalli S. Highly Active Antiretroviral Therapy (HAART). StatPearls 2022.
[73]
Wendelken LA, Jahanshad N, Rosen HJ, et al. ApoE ε4 is associated with cognition, brain integrity and atrophy in HIV over age 60. J Acquir Immune Def Syndr (1999) 2016; 73(4): 426.
[77]
Wadley AL, Cherry CL, Price P, Kamerman PR. HIV neuropathyrisk factors and symptom characterization in stavudine-exposed South Africans. J Pain Symptom Manage 2011; 41(4): 700-6.
[88]
Adam J, Ellis RJ. HIV in the cART era and the mitochondrial:immune interface in the CNS Mitochondrial Dysfunction inNeurodegeneration and Peripheral Neuropathies. (1st ed.). Amsterdam, Netherlands: Elsevier Inc. 2019; Vol. 145.
[89]
Roda RH, Hoke A. Mitochondrial dysfunction in HIVinducedperipheral neuropathy Mitochondrial Dysfunction inNeurodegeneration and Peripheral Neuropathies. (1st ed.). Amsterdam, Netherlands: Elsevier Inc. 2019; p. 145.
[100]
McDonnell J, Haddow L, Daskalopoulou M, et al. Minimal cognitive impairment in UK HIV-positive men who have sex with men: effect of case definitions and comparison with the general population and HIV-negative men. J Acquir Immune Deficien Syndr 1999; 67(2): 120.
[109]
Shlay JC, Chaloner K, Max MB, et al. Acupuncture and amitriptyline for paindue to HIV-related peripheral neuropathy: A randomized controlled trial. JAMA 1998; 280: 1590-5.
[137]
Strick LB, Wald A, Celum C. Management of herpes simplex virus type 2 infection in HIV type 1-infected persons. Clin Infect Dis 2006; 43(3): 347-56.
[139]
Linke-Serinsöz E, Fend F, Quintanilla-Martinez L. Human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) related lymphomas, pathology view point. In Seminars in diagnostic pathology 2017; 34(4): 352-63.
[142]
Chirico C, Izzo I, Casari S, Cattaneo C, Doglietto F, Castelli F. AIDS-associated central nervous system lymphoma: the great mime. A case report and literature review. IDTM 2018; 4(2): e472.
[143]
Esau D. Viral causes of lymphoma: The history of Epstein-Barr virus and human T-lymphotropic virus 1. Virology 2017; 8: 1178122X17731772.
[184]
Cohen O, Weissmal D, Fauci KS. The immune pathogenesis of HIV infection Fundamental Immunology. Philadelphia: Lippincott-Raven 1999; pp. 1455-509.