A modern view on the prevention and treatment of HIV-associated neurocognitive disorders
https://doi.org/10.30629/2658-7947-2022-27-5-5-13
Abstract
Acquired Immune Deficiency Syndrome (AIDS) is now considered one of the most global pandemics in human history. Despite the use of highly active antiretroviral therapy (HAART), HIV-1 infection is often accompanied by the development of CNS disorders, including neurocognitive disorders. The use of etiologic therapy has successfully prevented many of the possible terminal complications of the disease, but as patient survival time increases, the prevalence of cognitive impairment among AIDS patients is increasing. Theclinical manifestations of these disorders can rapidly progress from subtle attention deficits and behavioral disorders to the development of dementia. Diagnosing neurocognitive impairment in HIV-infected patients is usually difficult and requires consistent diagnostic procedures from the clinician, including initial screening and, if necessary, neuropsychiatric testing and neuroimaging. Early diagnosis and correction of neurocognitive impairment in HIV-infected individuals with adequate antiretroviral therapy is essential for successful treatment. The review also considers the use of drugs for the prevention and treatment of neurocognitive impairment, taking into account the peculiarities of persistence of the pathogen in the nervous system and the capabilities of modern medicine. One of the most promising methods of supporting therapy for such disorders is the delivery of antiretroviral drugs using various nanosystems (polymeric nanoparticles, lipid nanoparticles, nanogels, magnetic particles).
About the Authors
E .A. Egorova
Institute “Medical Academy n.a. S.I. Georgievsky” of Vernadskjy CFU
Russian Federation
Russian Federation
Simferopol
A. N. Useinova
Institute “Medical Academy n.a. S.I. Georgievsky” of Vernadskjy CFU
Russian Federation
Russian Federation
Simferopol
S. A. Abibulaev
Institute “Medical Academy n.a. S.I. Georgievsky” of Vernadskjy CFU
Russian Federation
Russian Federation
Simferopol
S. P. Mar'yanenko
Institute “Medical Academy n.a. S.I. Georgievsky” of Vernadskjy CFU
Russian Federation
Russian Federation
Simferopol
K. N. Koryanova
Pyatigorsk Medical and Pharmaceutical Institute, Branch of the Federal State Budgetary Educational Institution of Higher Education “Volgograd State Medical university” of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Pyatigorsk
References
1. Rojas-Celis V., Valiente-Echeverría F., Soto-Rifo R., ToroAscuy D. New Challenges of HIV-1 Infection: How HIV-1 Attacks and Resides in the Central Nervous System. Cells. 2019;8(10):1245. https://doi.org/10.3390/cells8101245
2. Joint United Nations Programme on HIV/AIDS. Global report: UNAIDS report on the global AIDS epidemic 2013. Joint United Nations Programme on HIV/AIDS; Geneva, Switzerland: 2013. [updated 2021 Dec 28; cited 2022 March 7]. Available from: http://www.unaids.org/sites/default/files/en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/UNAIDS_Global_Report_2013_en.pdf.
3. Смирнова А.А., Прахова Л.Н., Ильвес А.Г., Сельверстова Н.А., Резникова Т.Н., Катаева Г.В., Могонов Е.П. Нейропсихологические и морфометрические биомаркеры неблагоприятного прогноза у пациентов с легкими когнитивными нарушениями. Российский неврологический журнал. 2021;26(6):4–15. [Smirnova A.A., Prakhova L.N., Ilves A.G., Seliverstova N.A., Reznikova T.N., Kataeva G.V., Magonov E.P. Neuropsychological and morphometric biomarkers of poor prognosis in patients with mild cognitive impairment. Russian Neurological Journal (Rossijskij Nevrologicheskiy Zhurnal). 2021;26(6):4–15. (In Russ.)]. https://doi.org/10.30629/2658-7947-2021-26-6-4-15
4. Deeks S.G., Lewin S.R., Havlir D.V. The end of AIDS: HIV infection as a chronic disease. Lancet. 2013;382(9903):1525–33. https://doi.org/10.1016/S0140-6736(13)61809-7.
5. Toborek M, Lee Y.W., Flora G., Pu H., András I.E., Wylegala E. et al. MechБНРsms of the blood-brain barrier disruption in HIV-1 infection. Cell Mol Neurobiol. 2005;25(1):181–99. https://doi.org/10.1007/s10571-004-1383-x
6. Verma S., Lo Y., Chapagain M., Lum S., Kumar M., Gurjav U. et al. West Nile virus infection modulates human brain microvascular endothelial cells tight junction proteins and cell adhesion molecules: Transmigration across the in vitro blood-brain barrier. Virology. 2009;385(2):425–33. https://doi.org/10.1016/j.virol.2008.11.047
7. Peluso R., Haase A., Stowring L., Edwards M., Ventura P. A. Trojan Horse mechanism for the spread of visna virus in monocytes. Virology. 1985;147(1):231–6. https://doi.org/10.1016/0042-6822(85)90246-6
8. Zipeto D., Serena M., Mutascio S., Parolini F., Diani E., Guizzardi E. et al. HIV-1-Associated Neurocognitive Disorders: Is HLA-C Binding Stability to β2-Microglobulin a Missing Piece of the Pathogenetic Puzzle? Front Neurol. 2018;9:791. https://doi.org/10.3389/fneur.2018.00791
9. Fischer-Smith T., Rappaport J. Evolving paradigms in the pathogenesis of HIV-1-associated dementia. Expert Rev Mol Med. 2005;7(27):1–26. https://doi.org/10.1017/S1462399405010239
10. Евзельман М.А., Снимшикова И.А., Королева Л.Я. Неврологические осложнения ВИЧ-инфекции. Журнал неврологии и психиатрии. 2015;115(3):89–93. [Evzel’man M.A., Snimshhikova I.A., Koroleva L.Ia. Neurologic complications of HIV infection. Zhurnal nevrologii i psihiatrii (Journal of neurology and psychiatry).2015;115(3):89–93. (In Russ.)].
11. Kramer-Hämmerle S., Rothenaigner I., Wolff H., Bell J.E., Brack-Werner R. Cells of the central nervous system as targets and reservoirs of the human immunodeficiency virus. Virus Res. 2005;111(2):194–213. https://doi.org/10.1016/j.virusres.2005.04.009
12. Almeida O.P., Lautenschlager N.T. Dementia associated with infectious diseases. Int Psychogeriatr. 2005;17(1):65–77. https://doi.org/10.1017/s104161020500195x
13. Завалишина И.А., Спирина Н.Н., Бойко А.Н., Никитина С.С. Хронические нейроинфекции. Библиотека врача-специалиста. 2017;592 с. [Zavalishina I.A., Spirina N.N., Boyko A.N., Nikitina S.S. Chronic neuroinfections. 2017;592 p. (In Russ.)]. ISBN 978-5-9704-4056-8. Текст: электронный. URL: https://www.rosmedlib.ru/book/ISBN9785970440568.html (дата обращения: 10.03.2022).
14. Maschke M., Kastrup O., Esser S., Ross B., Hengge U., Hufnagel A. Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART). Neurol Neurosurg Psychiatry. 2000;69(3):376–80. https://doi.org/10.1136/jnnp.69.3.376
15. Ghafouri M., Amini S., Khalili K., Sawaya B.E. HIV-1 associated dementia: symptoms and causes. Retrovirology. 2006;3:28. https://doi.org/10.1186/1742-4690-3-28
16. Eisele E., Siliciano R.F. Redefining the viral reservoirs that prevent HIV-1 eradication. Immunity. 2012;37(3):377–88. https://doi.org/10.1016/j.immuni.2012.08.010
17. Cysique L.A., Maruff P., Brew B.J. Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts. Neurovirol. 2004;10(6):350–7. https://doi.org/10.1080/13550280490521078
18. Grant I., Franklin D.R. Jr, Deutsch R., Woods S.P., Vaida F., Ellis R.J. et al. CHARTER Group. Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology. 2014;82(23):2055–62. https://doi.org/10.1212/WNL.0000000000000492
19. Navia B.A., Jordan B.D., Price R.W. The AIDS dementia complex: I. Clinical features. Ann Neurol. 1986;19(6):517–24. https://doi.org/10.1002/ana.410190602
20. Navia B.A., Cho E.S., Petito C.K., Price R.W. The AIDS dementia complex: II. Neuropathology. Ann Neurol. 1986;19(6):525–35. https://doi.org/10.1002/ana.410190603
21. Stern Y., McDermott M.P., Albert S., Palumbo D., Selnes O.A., McArthur J. et al. Dana Consortium on the Therapy of HIV-Dementia and Related Cognitive Disorders. Factors associated with incident human immunodeficiency virus-dementia. Arch Neurol. 2001;58(3):473–9. https://doi.org/10.1001/archneur.58.3.473
22. Becker J.T., Kingsley L., Mullen J., Cohen B., Martin E., Miller E.N. et al. Multicenter AIDS Cohort Study. Vascular risk factors, HIV serostatus, and cognitive dysfunction in gay and bisexual men. Neurology. 2009;73(16):1292–9. https://doi.org/10.1212/WNL.0b013e3181bd10e7
23. Clifford D.B., Vaida F., Kao Y.T., Franklin D.R., Letendre S.L., Collier A.C. et al. CHARTER Group. Absence of neurocognitive effect of hepatitis C infection in HIV-coinfected people. Neurology. 2015;84(3):241–50. https://doi.org/10.1212/WNL.0000000000001156
24. Fabbiani M., Ciccarelli N., Tana M., Farina S., Baldonero E., Di Cristo V. et al. Cardiovascular risk factors and carotid intimamedia thickness are associated with lower cognitive performance in HIV-infected patients. HIV Med. 2013;14(3):136–44. https://doi.org/10.1111/j.1468-1293.2012.01044.x
25. Simioni S., Cavassini M., Annoni J.M., Rimbault Abraham A., Bourquin I., Schiffer V. et al. Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS. 2010;24(9):1243–1250. https://doi.org/10.1097/QAD.0b013e3283354a7b
26. Antinori A., Arendt G., Becker J.T., Brew B.J., Byrd D.A., Cherner M. et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69(18):1789–99. https://doi.org/10.1212/01
27. Clifford D.B., Ances B.M. HIV-associated neurocognitive disorder. Lancet Infect Dis. 2013;13(11):976–86. https://doi.org/10.1016/S1473-3099(13)70269-X
28. Трофимова Т.Н., Катаева Г.В., Громова Е.А., Рассохин В.В., Боева Е.В., Симакина О.Е., Беляков Н.А. ВИЧ-ассоциированные нейрокогнитивные расстройства: диагностика, выявление причин и эффективность терапии. ВИЧ-инфекция и иммуносупрессивные расстройства. 2018;10(4):7–24. [Trofimova T.N., Katayeva G.V., Gromova E.A., Rassokhin V.V., Boeva E.V., Simakina O.E., Belyakov N.A. HIV-associated neurocognitive disorders: diagnosis, detection of causes and therapy efficiency. HIV Infection and Immunosuppressive Disorders. 2018;10(4):7–24. (In Russ.)]. https://doi.org/10.22328/2077-9828-2018-10-4-7-24/
29. Mitra P., Sharman T. HIV Neurocognitive Disorders. [Updated 2021 Jun 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022;Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK555954/
30. Tozzi V., Balestra P., Bellagamba R., Corpolongo A., Salvatori M.F., Visco-Comandini U. et al. Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors. Acquir Immune Defic Syndr. 2007;45(2):174–82. https://doi.org/10.1097/QAI.0b013e318042e1ee
31. Heaton R.K., Clifford D.B., Franklin D.R. Jr, Woods S.P., Ake C., Vaida F. et al. CHARTER Group. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy:CHARTER Study. Neurology. 2010;75(23):2087–96. https://doi.org/10.1212/WNL.0b013e318200d727
32. Underwood J., Robertson K.R., Winston A. Could antiretroviral neurotoxicity play a role in the pathogenesis of cognitive impairment in treated HIV disease? AIDS. 2015;29(3):253–61. https://doi.org/10.1097/QAD.0000000000000538
33. Vassallo M., Fabre R., Durant J., Lebrun-Frenay C., Joly H., Ticchioni M. et al. A decreasing CD4/CD8 ratio over time andlower CSF-penetrating antiretroviral regimens are associated with a higher risk of neurocognitive deterioration, independently of viral replication. Neurovirol. 2017;23(2):216–225. https://doi.org/10.1007/s13365-016-0490-z
34. Клинические рекомендации. Текст: электронный. Министерство здравоохранения Российской Федерации: [сайт]. URL: http://rushiv.ru/wp-content/uploads/2020/06/KR79-ot-21.04.20.pdf (дата обращения: 10.03.2022).
35. Ellis R.J., Badiee J., Vaida F., Letendre S., Heaton R.K., Clifford D. et al. CHARTER Group. CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. AIDS. 2011;25(14):1747–51. https://doi.org/1097/QAD.0b013e32834a40cd
36. Lin S.P., Calcagno A., Letendre S.L., Ma Q. Clinical Treatment Options and Randomized Clinical Trials for Neurocognitive Complications of HIV Infection: Combination Antiretroviral Therapy, Central Nervous System Penetration Effectiveness, and Adjuvants. Curr Top Behav Neurosci. 2021;50:517–545. https://doi.org/10.1007/7854_2020_186
37. Reeve E., Farrell B., Thompson W., Herrmann N., Sketris I., Magin P.J. et al. Deprescribing cholinesterase inhibitors and memantine in dementia: guideline summary. Med J Aust. 2019;210(4):174–179. https://doi.org/10.5694/mja2.50015
38. Asahchop E.L., Meziane O., Mamik M.K., Chan W.F., Branton W.G., Resch L. et al. Reduced antiretroviral drug efficacy and concentration in HIV-infected microglia contributes to viral persistence in brain. Retrovirology. 2017;14(1):47. https://doi.org/10.1186/s12977-017-0370-5
39. Churchill M.J., Deeks S.G., Margolis D.M., Siliciano R.F., Swanstrom R. HIV reservoirs: what, where and how to target them. Nat Rev Microbiol. 2016;14(1):55–60. https://doi.org/10.1038/nrmicro.2015.5
40. Nowacek A., Gendelman H.E., Nano Ar.T. neuroAIDS and CNS drug delivery. Nanomedicine. 2009;4(5):557–74. https://doi.org/10.2217/nnm.09.38
41. Ene L., Duiculescu D., Ruta S.M. How much do antiretroviral drugs penetrate into the central nervous system? J Med Life. 2011;4(4):432–9. PMID: 22514580; PMCID: PMC3227164.
42. Letendre S.L., Ellis R.J., Everall I., Ances B., Bharti A., McCutchan J.A. Neurologic complications of HIV disease and their treatment. Top HIV Med. 2009;17(2):46–56. PMID: 19401607; PMCID: PMC3065886.
43. Fiandra L., Capetti A., Sorrentino L., Corsi F. Nanoformulated Antiretrovirals for Penetration of the Central Nervous System:State of the Art. Neuroimmune Pharmacol. 2017;12(1):17–30. https://doi.org/10.1007/s11481-016-9716-3
44. Saksena N.K., Wang B., Zhou L., Soedjono M., Ho Y.S., Conceicao V. HIV reservoirs in vivo and new strategies for possible eradication of HIV from the reservoir sites. HIV AIDS. 2010;2:103–22. https://doi.org/10.2147/hiv.s6882
45. Усеинова А.Н., Егорова Е.А., Марьяненко С.П., Иванцова Н.Л. Наносистемы для доставки антиретровирусных лекарственных средств: возможности, проблемы и перспективы. ВИЧ-инфекция и иммуносупрессии. 2021;13(4):64–76. [Useinova A.N., Egorova E.A., Mar’yanenko S.P., Ivancova N.L. Nanosystems for the delivery of antiretroviral drugs: opportunities, problems and prospects. J HIV infection and immunosuppression. 2021;13(4):64–76. (In Russ.)]. https://doi.org/10.22328/2077-9828-2021-13-4-64-76
46. Brittany B.L., Fattahi, P., Brown, J.L. Polymeric nanoparticles: the future of nanomedicine. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 2016;8(2):271–299. https://doi.org/10.1002/wnan.1364
47. Rao S., Morales A.A., Pearse D.D. The Comparative Utility of Viromer RED and Lipofectamine for Transient Gene Introduction into Glial Cells. Biomed Res Int. 2015;2015:458624. https:// doi.org/10.1155/2015/458624
48. Saiyed Z.M., Gandhi N.H., Nair M.P. Magnetic nanoformulation of azidothymidine 5’-triphosphate for targeted delivery across the blood-brain barrier. International journal of nanomedicine. 2010;5:157. https://doi.org/10.2147/IJN.S8905
49. Lu W. Adsorptive-mediated brain delivery systems. Current pharmaceutical biotechnology. 2012;13(12):2340–2348. https://doi.org/10.2174/138920112803341851
50. Su S., M Kang P. Recent Advances in Nanocarrier-Assisted Therapeutics Delivery Systems. Pharmaceutics. 2020;12(9):837. https://doi.org/10.3390/pharmaceutics12090837
51. Chhabra R., Tosi G., Grabrucker A.M. Emerging use of nanotechnology in the treatment of neurological disorders. Current pharmaceutical design. 2015;21(22):3111–3130. https://doi.org/10.2174/1381612821666150531164124
52. Sagar V., Pilakka‐Kanthikeel S., Pottathil R., Saxena S.K., Nair M. Towards nanomedicines for neuroAIDS. Reviews in medical virology. 2014;24(2):103–124. https://doi.org/10.1038/s41598-020-60684-1
53. Sadowski I., Hashemi F.B. Strategies to eradicate HIV from infected patients: elimination of latent provirus reservoirs. Cell Mol Life Sci. 2019;76(18):3583–3600. https://doi.org/10.1007/s00018-019-03156-8
54. Ebina K., Hirano T., Maeda Y., Yamamoto W., Hashimoto M., Koichi M. et al. Drug retention of 7 biologics and tofacitinib in biologics-naïve and biologics-switched patients with rheumatoid arthritis: the ANSWER cohort study. Arthritis Res Ther.2020;22:142. https://doi.org/10.1186/s13075-020-02232-w
55. Lorenzo-Redondo R., Fryer H.R., Bedford T., Kim E.Y., Archer J., Pond S.L.K. et al. Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature. 2016;530(7588):51–56. https://doi.org/10.1038/nature16933.
56. Kumar S., Vimal K.M., Himanshu R.D., Madan L.B., Bhatt S., Shailendra K. Global Perspective of Novel Therapeutic Strategies for the Management of NeuroAIDS: Novel drug delivery methods for NeuroAIDS. Biomolecular Concepts. 2018;9(1):33–42. https://doi.org/10.1515/bmc-2018-0005
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Egorova E..., Useinova A.N., Abibulaev S.A., Mar'yanenko S.P., Koryanova K.N. A modern view on the prevention and treatment of HIV-associated neurocognitive disorders. Russian neurological journal. 2022;27(5):5-13. (In Russ.) https://doi.org/10.30629/2658-7947-2022-27-5-5-13
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