HIV-Associated Neurocognitive Disorder (HAND) and the Prospect of Brain-Penetrating Protease Inhibitors for Antiretroviral Treatment
Main Article Content
Abstract
The advent of combined antiretroviral therapy (cART) has dramatically improved HIV management and patient care of HIV-infected individuals. The cART regimen resulted in a significant reduction of HIV/AIDS-related mortality and greatly improved life expectancies of those patients with access to cART. However, among many HIV-related complications, neurocognitive dysfunction, known as HIV-associated neurocognitive disorder (HAND), has now been a major issue. While the cART regimen has been effective in reduction of HAND in many patients, the prevalence of HAND is increasing as HIV/AIDS patients live longer. HIV infection and its subsequent manifestation of HAND is complex. It is evident that the brain can serve as a sanctuary for HIV replication and HAND can remain in patients even with cART treatment due to poor blood-brain barrier permeability of the majority of current antiretroviral agents. Conceivably, cART needs to have improved central nervous system (CNS) penetration properties for effective treatment and possible prevention of HAND. Therefore, design and development of new antiretroviral agents that can penetrate into the CNS effectively, could block HIV replication and significantly reduce the viral load in the CNS. This may prevent HAND and related symptoms. HIV protease inhibitors (PIs) are a critical component of cART. Over the years, we have designed and synthesized a range of highly potent and novel PIs including the FDA approved drug, darunavir, which has been used as a first-line treatment. In an effort to improve CNS penetration, we have been involved in the design and development of potent PIs with improved in vitro brain penetration properties. Herein we provide a brief review that covers insights and discussion of HAND and our work on PI development to ameliorate HIV-associated neurocognitive disorders.
Article Details
How to Cite
GHOSH, Arun K.; SARKAR, Anindya; MITSUYA, Hiroaki.
HIV-Associated Neurocognitive Disorder (HAND) and the Prospect of Brain-Penetrating Protease Inhibitors for Antiretroviral Treatment.
Medical Research Archives, [S.l.], v. 5, n. 4, apr. 2017.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1113>. Date accessed: 15 dec. 2024.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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[12] Lohse N, Hansen AB, Gerstoft J, Obel N. Improved survival in HIV-infected persons: consequences and perspectives. J Antimicrob Chemother. 2007;60(3):461–463.
[13] Zhou L, Saksena NK. HIV associated neurocognitive disorders. Infect Dis Rep. 2013;5(suppl 1): e8. www.ncbi.nlm.nih.gov/pmc/articles/ PMC3892625/pdf/idr-2013-s1-e8.pdf.
[14] Takahashi K, Wesselingh SL, Griffin DE, McArthur JC, Johnson RT, Glass JD. Localization of HIV-1 in human brain using polymerase chain reaction/in situ hybridization and immunocytochemistry. Ann Neurol. 1996;39(6):705–711.
[15] Müller M, Wandel S, Colebunders R, Attia S, Furrer H, Egger M. Immune reconstitution
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[16] Rani P, Thomas FP. Central Nervous System Complications in HIV. Medscape. Dec 23, 2015. Retrieved from http://emedicine.medscape.com/article/1167008-overview.
[17] Heaton RK, Clifford DB, Franklin DR Jr, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I; CHARTER Group. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010;75(23):2087-2096.
[18] Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69(18):1789-1799.
[19] Simoes E, Justino JD. HIV-associated neurocognitive disorders: A review for NPs. The Nurse Practitioner. 2015;40(7):1–7.
[20] Clifford DB, Ances BM. HIV-associated neurocognitive disorder. Lancet Infect Dis. 2013;13(11):976–986.
[21] Price RW, Spudich S. Antiretroviral therapy and central nervous system HIV-1 infection. J Infect Dis. 2008;197(Suppl 3):S294-S306.
[22] Vazeux R, Brousse N, Jarry A, Henin D, Marche C, Vedrenne C, Mikol J, Wolff M, Michon C, Rozenbaum W, et al. AIDS subacute encephalitis. Identification of HIV-infected cells. Am J Pathol. 1987;126(3):403-410.
[23] Rawson T, Muir D, Mackie NE, Garvey LJ, Everitt A, Winston A. Factors associated with cerebrospinal fluid HIV RNA in HIV infected subjects undergoing lumbar puncture examination in a clinical setting. J Infect. 2012;65(3):239–245.
[24] Cysique LA, Vaida F, Letendre S, Gibson S, Cherner M, Woods SP, McCutchan JA, Heaton RK, Ellis RJ. Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. Neurology. 2009;73(5):342-348.
[25] Price RW, Brew B, Sidtis J, Rosenblum M, Scheck AC, Cleary P. The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science. 1988;239(4840):586–592.
[26] Brew B, Rosenblum M, Cronin K, Price R. AIDS dementia complex and HIV-1 brain infection: clinical-virological correlations. Annals of Neurology. 1995;38(4):563–570.
[27] Nabha L, Duong L, Timpone J. HIV-associated neurocognitive disorders: perspective on management strategies. Drugs. 2013;73(9):893-905.
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