OpenLB
Open Library of Bioscience
Advanced Search
Reviews in the neurosciences
Mar 06, 2025;

Evolving strategies in the diagnosis and treatment of HIV-associated neurocognitive disorders.

Chuanke Hou, Jingwei Wei, Hui Zhang, Hongjun Li
Author Information
  1. Chuanke Hou: Department of Radiology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
  2. Jingwei Wei: Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
  3. Hui Zhang: School of Engineering Medicine, Beihang University, Beijing, 100191, China.
  4. Hongjun Li: Department of Radiology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
PMID: 40038242 DOI: 10.1515/revneuro-2025-0004

Abstract

Despite significant progress in managing HIV infection, HIV - associated neurocognitive disorder (HAND) continues to be a concern even among HIV individuals with well - controlled infection. Current diagnostic strategies, primarily reliant on neuropsychological tests, neuroimaging, and biomarkers from blood and cerebrospinal fluid, alongside combination antiretroviral therapy, form the foundation of HAND management. However, these strategies often fail to identify early or mild HAND, particularly asymptomatic neurocognitive impairment, resulting in delayed diagnosis and intervention. Furthermore, the inability to perform in-depth molecular analyses and conduct longitudinal tracking limits therapeutic advancements. Emerging technologies - advanced neuroimaging, multi-omics, artificial intelligence, alongside simian immunodeficiency virus non-human primate models - are revolutionizing the field. These innovations offer unprecedented opportunities for deeper understanding of the disease mechanism, early detection, comprehensive monitoring, and personalized treatment strategies. Integrating these cutting-edge tools promises to reshape the landscape of HAND management, enhancing the quality of life for those living with HIV.

Keywords

HIV-associated neurocognitive disorders Simian Immunodeficiency Virus artificial intelligence multiomics neuroimaging

References

  1. Abidin, A.Z., DSouza, A.M., Nagarajan, M.B., Wang, L., Qiu, X., Schifitto, G., and Wismüller, A. (2018). Alteration of brain network topology in HIV-associated neurocognitive disorder: a novel functional connectivity perspective. Neuroimage. Clin. 17: 768–777, https://doi.org/10.1016/j.nicl.2017.11.025 . [DOI: 10.1016/j.nicl.2017.11.025]
  2. Abidin, A.Z., DSouza, A.M., Schifitto, G., and Wismüller, A. (2020). Detecting cognitive impairment in HIV-infected individuals using mutual connectivity analysis of resting state functional MRI. J. Neurovirol. 26: 188–200, https://doi.org/10.1007/s13365-019-00823-1 . [DOI: 10.1007/s13365-019-00823-1]
  3. Allers, K. and Schneider, T. (2015). CCR5Δ32 mutation and HIV infection: basis for curative HIV therapy. Curr. Opin. Virol. 14: 24–29, https://doi.org/10.1016/j.coviro.2015.06.007 . [DOI: 10.1016/j.coviro.2015.06.007]
  4. Andres, M.A., Feger, U., Nath, A., Munsaka, S., Jiang, C.S., and Chang, L. (2011). APOE ε4 allele and CSF APOE on cognition in HIV-infected subjects. J. Neuroimmune. Pharmacol. 6: 389–398, https://doi.org/10.1007/s11481-010-9254-3 . [DOI: 10.1007/s11481-010-9254-3]
  5. Antinori, A., Arendt, G., Becker, J.T., Brew, B.J., Byrd, D.A., Cherner, M., Clifford, D.B., Cinque, P., Epstein, L.G., Goodkin, K., et al.. (2007). Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69: 1789–1799, https://doi.org/10.1212/01.wnl.0000287431.88658.8b . [DOI: 10.1212/01.wnl.0000287431.88658.8b]
  6. Bannister, A.J. and Kouzarides, T. (2011). Regulation of chromatin by histone modifications. Cell. Res 21: 381–395, https://doi.org/10.1038/cr.2011.22 . [DOI: 10.1038/cr.2011.22]
  7. Boerwinkle, A.H., Strain, J.F., Burdo, T., Doyle, J., Christensen, J., Su, Y., Wisch, J.K., Cooley, S.A., Vaida, F., Smith, M.D., et al.. (2020). Comparison of [11C]-PBR28 binding between persons living with HIV and HIV-uninfected individuals. J. Acquir. Immune. Defic. Syndr. 85: 244–251, https://doi.org/10.1097/qai.0000000000002435 . [DOI: 10.1097/qai.0000000000002435]
  8. Borges, Á.H., O’Connor, J.L., Phillips, A.N., Rönsholt, F.F., Pett, S., Vjecha, M.J., French, M.A., and Lundgren, J.D., and INSIGHT SMART and ESPRIT Study Groups and the SILCAAT Scientific Committee (2015). Factors associated with plasma IL-6 levels during HIV infection. J. Infect. Dis. 212: 585–595, https://doi.org/10.1093/infdis/jiv123 . [DOI: 10.1093/infdis/jiv123]
  9. Boulware, D.R., Hullsiek, K.H., Puronen, C.E., Rupert, A., Baker, J.V., French, M.A., Bohjanen, P.R., Novak, R.M., Neaton, J.D., Sereti, I., et al.. (2011). Higher levels of CRP, D-dimer, IL-6, and hyaluronic acid before initiation of antiretroviral therapy (ART) are associated with increased risk of AIDS or death. J. Infect. Dis. 203: 1637–1646, https://doi.org/10.1093/infdis/jir134 . [DOI: 10.1093/infdis/jir134]
  10. Brabers, N.a. C.H. and Nottet, H.S.L.M. (2006). Role of the pro-inflammatory cytokines TNF-alpha and IL-1beta in HIV-associated dementia. Eur. J. Clin. Invest. 36: 447–458, https://doi.org/10.1111/j.1365-2362.2006.01657.x . [DOI: 10.1111/j.1365-2362.2006.01657.x]
  11. Ceccarelli, G., Brenchley, J.M., Cavallari, E.N., Scheri, G.C., Fratino, M., Pinacchio, C., Schietroma, I., Fard, S.N., Scagnolari, C., Mezzaroma, I., et al.. (2017). Impact of high-dose multi-strain probiotic supplementation on neurocognitive performance and central nervous system immune activation of HIV-1 infected individuals. Nutrients 9: 1269, https://doi.org/10.3390/nu9111269 . [DOI: 10.3390/nu9111269]
  12. Ceccarelli, G., Fratino, M., Selvaggi, C., Giustini, N., Serafino, S., Schietroma, I., Corano Scheri, G., Pavone, P., Passavanti, G., Fegatelli, A., et al.. (2017). A pilot study on the effects of probiotic supplementation on neuropsychological performance and microRNA-29a-c levels in antiretroviral-treated HIV-1-infected patients. Brain. Behav. 7: e00756, https://doi.org/10.1002/brb3.756 . [DOI: 10.1002/brb3.756]
  13. Chaganti, J. and Brew, B.J. (2021). MR spectroscopy in HIV associated neurocognitive disorder in the era of cART: a review. AIDS. Res. Ther 18: 65, https://doi.org/10.1186/s12981-021-00388-2 . [DOI: 10.1186/s12981-021-00388-2]
  14. Chen, X., Wei, J., Li, Z., Zhang, Y., Zhang, X., Zhang, L., Wang, X., Zhang, Y., and Zhang, T. (2024). Dysregulation of gut microbiota-derived neuromodulatory amino acid metabolism in human immunodeficiency virus-associated neurocognitive disorder: an integrative metagenomic and metabolomic analysis. Ann. Neurol. 96: 306–320, https://doi.org/10.1002/ana.26963 . [DOI: 10.1002/ana.26963]
  15. CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) group , McGuire, J.L., Gill, A.J., Douglas, S.D., and Kolson, D.L. (2015). Central and peripheral markers of neurodegeneration and monocyte activation in HIV-associated neurocognitive disorders. J. Neurovirol. 21: 439–448, https://doi.org/10.1007/s13365-015-0333-3 . [DOI: 10.1007/s13365-015-0333-3]
  16. Cotto, B., Natarajanseenivasan, K., and Langford, D. (2019). HIV-1 infection alters energy metabolism in the brain: contributions to HIV-associated neurocognitive disorders. Prog. Neurobiol. 181: 101616, https://doi.org/10.1016/j.pneurobio.2019.101616 . [DOI: 10.1016/j.pneurobio.2019.101616]
  17. Cysique, Lucette A. and Rourke, Sean B. (2021). Neurocognitive Complications of HIV-infection: Neuropathogenesis to Implications for clinical practice . Springer International Publishing AG, Springer, New York.
  18. Day, T.R.C., Smith, D.M., Heaton, R.K., Franklin, D., Tilghman, M.W., Letendre, S., Jin, H., Wu, Z., Shi, C., Yu, X., et al.. (2016). Subtype associations with HIV-associated neurocognitive disorder in China. J. Neurovirol. 22: 246–250, https://doi.org/10.1007/s13365-015-0377-4 . [DOI: 10.1007/s13365-015-0377-4]
  19. Dhillon, N.K., Williams, R., Callen, S., Zien, C., Narayan, O., and Buch, S. (2008). Roles of MCP-1 in development of HIV-dementia. Front. Biosci. 13: 3913–3918, https://doi.org/10.2741/2979 . [DOI: 10.2741/2979]
  20. Di Liberto, G., Egervari, K., Kreutzfeldt, M., Schürch, C.M., Hewer, E., Wagner, I., Du Pasquier, R., and Merkler, D. (2022). Neurodegenerative phagocytes mediate synaptic stripping in Neuro-HIV. Brain 145: 2730–2741, https://doi.org/10.1093/brain/awac102 . [DOI: 10.1093/brain/awac102]
  21. Dickens, A.M., Anthony, D.C., Deutsch, R., Mielke, M.M., Claridge, T.D.W., Grant, I., Franklin, D., Rosario, D., Marcotte, T., Letendre, S., et al.. (2015). Cerebrospinal fluid metabolomics implicate bioenergetic adaptation as a neural mechanism regulating shifts in cognitive states of HIV-infected patients. AIDS 29: 559–569, https://doi.org/10.1097/qad.0000000000000580 . [DOI: 10.1097/qad.0000000000000580]
  22. Dolan, M.J., Kulkarni, H., Camargo, J.F., He, W., Smith, A., Anaya, J.-M., Miura, T., Hecht, F.M., Mamtani, M., Pereyra, F., et al.. (2007). CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms. Nat. Immunol. 8: 1324–1336, https://doi.org/10.1038/ni1521 . [DOI: 10.1038/ni1521]
  23. Fields, J.A., Spencer, B., Swinton, M., Qvale, E.M., Marquine, M.J., Alexeeva, A., Gough, S., Soontornniyomkij, B., Valera, E., Masliah, E., et al.. (2018). Alterations in brain TREM2 and Amyloid-β levels are associated with neurocognitive impairment in HIV-infected persons on antiretroviral therapy. J. Neurochem. 147: 784–802, https://doi.org/10.1111/jnc.14582 . [DOI: 10.1111/jnc.14582]
  24. Gannon, P.J., Akay-Espinoza, C., Yee, A.C., Briand, L.A., Erickson, M.A., Gelman, B.B., Gao, Y., Haughey, N.J., Zink, M.C., Clements, J.E., et al.. (2017). HIV protease inhibitors alter amyloid precursor protein processing via β-site amyloid precursor protein cleaving enzyme-1 translational up-regulation. Am. J. Pathol. 187: 91–109, https://doi.org/10.1016/j.ajpath.2016.09.006 . [DOI: 10.1016/j.ajpath.2016.09.006]
  25. Garcia-Mesa, Y., Xu, H.N., Vance, P., Gruenewald, A.L., Garza, R., Midkiff, C., Alvarez-Hernandez, X., Irwin, D.J., Gill, A.J., and Kolson, D.L. (2021). Dimethyl fumarate, an approved multiple sclerosis treatment, reduces brain oxidative stress in SIV-infected rhesus macaques: potential therapeutic repurposing for HIV neuroprotection. Antioxidants 10: 416, https://doi.org/10.3390/antiox10030416 . [DOI: 10.3390/antiox10030416]
  26. Gisslén, M., Price, R.W., Andreasson, U., Norgren, N., Nilsson, S., Hagberg, L., Fuchs, D., Spudich, S., Blennow, K., and Zetterberg, H. (2016). Plasma concentration of the neurofilament light protein (NFL) is a biomarker of CNS injury in HIV infection: a cross-sectional study. EBioMedicine 3: 135–140, https://doi.org/10.1016/j.ebiom.2015.11.036 . [DOI: 10.1016/j.ebiom.2015.11.036]
  27. Gisslén, M., Price, R.W., and Nilsson, S. (2011). The definition of HIV-associated neurocognitive disorders: are we overestimating the real prevalence? BMC. Infect. Dis. 11: 356, https://doi.org/10.1186/1471-2334-11-356 . [DOI: 10.1186/1471-2334-11-356]
  28. Guha, D., Misra, V., Yin, J., Horiguchi, M., Uno, H., and Gabuzda, D. (2023). Vascular injury markers associated with cognitive impairment in people with HIV on suppressive antiretroviral therapy. AIDS 37: 2137–2147, https://doi.org/10.1097/qad.0000000000003675 . [DOI: 10.1097/qad.0000000000003675]
  29. Guha, D., Nagilla, P., Redinger, C., Srinivasan, A., Schatten, G.P., and Ayyavoo, V. (2012). Neuronal apoptosis by HIV-1 Vpr: contribution of proinflammatory molecular networks from infected target cells. J. Neuroinflammation 9: 138, https://doi.org/10.1186/1742-2094-9-138 . [DOI: 10.1186/1742-2094-9-138]
  30. Hagberg, L., Edén, A., Zetterberg, H., Price, R.W., and Gisslén, M. (2022). Blood biomarkers for HIV infection with focus on neurologic complications—a review. Acta. Neurol. Scand. 146: 56–60, https://doi.org/10.1111/ane.13629 . [DOI: 10.1111/ane.13629]
  31. Harezlak, J., Buchthal, S., Taylor, M., Schifitto, G., Zhong, J., Daar, E., Alger, J., Singer, E., Campbell, T., Yiannoutsos, C., et al.. (2011). Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment. AIDS 25: 625–633, https://doi.org/10.1097/qad.0b013e3283427da7 . [DOI: 10.1097/qad.0b013e3283427da7]
  32. Imp, B.M., Rubin, L.H., Tien, P.C., Plankey, M.W., Golub, E.T., French, A.L., and Valcour, V.G. (2017). Monocyte activation is associated with worse cognitive performance in HIV-infected women with virologic suppression. J. Infect. Dis. 215: 114–121, https://doi.org/10.1093/infdis/jiw506 . [DOI: 10.1093/infdis/jiw506]
  33. Lamers, S.L., Fogel, G.B., Liu, E.S., Barbier, A.E., Rodriguez, C.W., Singer, E.J., Nolan, D.J., Rose, R., and McGrath, M.S. (2018). Brain-specific HIV Nef identified in multiple patients with neurological disease. J. Neurovirol. 24: 1–15, https://doi.org/10.1007/s13365-017-0586-0 . [DOI: 10.1007/s13365-017-0586-0]
  34. Lentz, M.R., Kim, W.-K., Kim, H., Soulas, C., Lee, V., Venna, N., Halpern, E.F., Rosenberg, E.S., Williams, K., and González, R.G. (2011). Alterations in brain metabolism during the first year of HIV infection. J. Neurovirol. 17: 220–229, https://doi.org/10.1007/s13365-011-0030-9 . [DOI: 10.1007/s13365-011-0030-9]
  35. Letendre, S.L., Zheng, J.C., Kaul, M., Yiannoutsos, C.T., Ellis, R.J., Taylor, M.J., Marquie-Beck, J., Navia, B., and HIV Neuroimaging Consortium . (2011). Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals. J. Neurovirol. 17: 63–69, https://doi.org/10.1007/s13365-010-0013-2 . [DOI: 10.1007/s13365-010-0013-2]
  36. Levine, A.J., Singer, E.J., Sinsheimer, J.S., Hinkin, C.H., Papp, J., Dandekar, S., Giovanelli, A., and Shapshak, P. (2009). CCL3 genotype and current depression increase risk of HIV-associated dementia. Neurobehav. HIV. Med 1: 1–7, https://doi.org/10.2147/nbhiv.s6820 . [DOI: 10.2147/nbhiv.s6820]
  37. Li, R., Gao, Y., Wang, W., Jiao, Z., Rao, B., Liu, G., and Li, H. (2022). Altered gray matter structural covariance networks in drug-naïve and treated early HIV-infected individuals. Front. Neurol. 13: 869871, https://doi.org/10.3389/fneur.2022.869871 . [DOI: 10.3389/fneur.2022.869871]
  38. Li, R., Qi, Y., Shi, L., Wang, W., Zhang, A., Luo, Y., Kung, W.K., Jiao, Z., Liu, G., Li, H., et al.. (2021). Brain volumetric alterations in preclinical HIV-associated neurocognitive disorder using automatic brain quantification and segmentation tool. Front. Neurosci. 15: 713760, https://doi.org/10.3389/fnins.2021.713760 . [DOI: 10.3389/fnins.2021.713760]
  39. Liao, Y.-J., Chen, J.-M., Long, J.-Y., Zhou, Y.-J., Liang, B.-Y., and Zhou, Y. (2020). Tanshinone IIA alleviates CCL2-induced leaning memory and cognition impairment in rats: a potential therapeutic approach for HIV-associated neurocognitive disorder. Biomed. Res. Int. 2020: 2702175, https://doi.org/10.1155/2020/5834542 . [DOI: 10.1155/2020/5834542]
  40. Liu, D., Liu, J., Xu, T., Qiao, H., Qi, Y., Gao, Y., Ailixire, N, Gao, L., Li, C., Xia, M., et al.. (2021). Longitudinal trajectories of brain volume in combined antiretroviral therapy treated and untreated simian immunodeficiency virus-infected rhesus macaques. AIDS 35: 2433–2443, https://doi.org/10.1097/qad.0000000000003055 . [DOI: 10.1097/qad.0000000000003055]
  41. Luckett, P.H., Paul, R.H., Hannon, K., Lee, J.J., Shimony, J.S., Meeker, K.L., Cooley, S.A., Boerwinkle, A.H., and Ances, B.M. (2021). Modeling the effects of HIV and aging on resting-state networks using machine learning. J. Acquir. Immune. Defic. Syndr. 88: 414–419, https://doi.org/10.1097/qai.0000000000002783 . [DOI: 10.1097/qai.0000000000002783]
  42. McArthur, J.C., McClernon, D.R., Cronin, M.F., Nance-Sproson, T.E., Saah, A.J., St Clair, M., and Lanier, E.R. (1997). Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain. Ann. Neurol. 42: 689–698, https://doi.org/10.1002/ana.410420504 . [DOI: 10.1002/ana.410420504]
  43. Mielke, M.M., Bandaru, V.V.R., McArthur, J.C., Chu, M., and Haughey, N.J. (2010). Disturbance in cerebral spinal fluid sphingolipid content is associated with memory impairment in subjects infected with the human immunodeficiency virus. J. Neurovirol. 16: 445–456, https://doi.org/10.1007/bf03210850 . [DOI: 10.1007/bf03210850]
  44. Nightingale, S., Ances, B., Cinque, P., Dravid, A., Dreyer, A.J., Gisslén, M., Joska, J.A., Kwasa, J., Meyer, A.-C., Mpongo, N., et al.. (2023). Cognitive impairment in people living with HIV: consensus recommendations for a new approach. Nat. Rev. Neurol. 19: 424–433, https://doi.org/10.1038/s41582-023-00813-2 . [DOI: 10.1038/s41582-023-00813-2]
  45. Nir, T.M., Jahanshad, N., Ching, C.R.K., Cohen, R.A., Harezlak, J., Schifitto, G., Lam, H.Y., Hua, X., Zhong, J., Zhu, T., et al.. (2019). Progressive brain atrophy in chronically infected and treated HIV+ individuals. J. Neurovirol. 25: 342–353, https://doi.org/10.1007/s13365-019-00723-4 . [DOI: 10.1007/s13365-019-00723-4]
  46. Obiabo, Y.O., Ogunrin, O.A., and Ogun, A.S. (2012). Effects of highly active antiretroviral therapy on cognitive functions in severely immune-compromised HIV-seropositive patients. J. Neurol. Sci. 313: 115–122, https://doi.org/10.1016/j.jns.2011.09.011 . [DOI: 10.1016/j.jns.2011.09.011]
  47. O’Connor, E.E., Sullivan, E.V., Chang, L., Hammoud, D.A., Wilson, T.W., Ragin, A.B., Meade, C.S., Coughlin, J., and Ances, B.M. (2023). Imaging of brain structural and functional effects in people with human immunodeficiency virus. J. Infect. Dis. 227: S16–S29, https://doi.org/10.1093/infdis/jiac387 . [DOI: 10.1093/infdis/jiac387]
  48. Papadopoulos, V., Baraldi, M., Guilarte, T.R., Knudsen, T.B., Lacapère, J.-J., Lindemann, P., Norenberg, M.D., Nutt, D., Weizman, A., Zhang, M.-R., et al.. (2006). Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol. Sci. 27: 402–409, https://doi.org/10.1016/j.tips.2006.06.005 . [DOI: 10.1016/j.tips.2006.06.005]
  49. Pendyala, G. and Fox, H.S. (2010). Proteomic and metabolomic strategies to investigate HIV-associated neurocognitive disorders. Genome. Med. 2: 22, https://doi.org/10.1186/gm143 . [DOI: 10.1186/gm143]
  50. Qi, Y., Wang, W., Rao, B., Yang, X., Yu, W., Li, J., Sun, Z., Zhou, F., Li, Y., Guo, Y., et al.. (2023). Value of radiomic analysis combined with diffusion tensor imaging in early diagnosis of HIV ‐associated neurocognitive disorders. J. Magn. Reson. Imaging. 58: 1882–1891, https://doi.org/10.1002/jmri.28741 . [DOI: 10.1002/jmri.28741]
  51. Ragin, A.B., Wu, Y., Gao, Y., Keating, S., Du, H., Sammet, C., Kettering, C.S., and Epstein, L.G. (2015). Brain alterations within the first 100 days of HIV infection. Ann. Clin. Transl. Neurol. 2: 12–21, https://doi.org/10.1002/acn3.136 . [DOI: 10.1002/acn3.136]
  52. Rizvi, S. and Khan, A.M. (2019). Use of transcranial magnetic stimulation for depression. Cureus 11: e4736, https://doi.org/10.7759/cureus.4736 . [DOI: 10.7759/cureus.4736]
  53. Robertson, K.R., Smurzynski, M., Parsons, T.D., Wu, K., Bosch, R.J., Wu, J., McArthur, J.C., Collier, A.C., Evans, S.R., and Ellis, R.J. (2007). The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 21: 1915–1921, https://doi.org/10.1097/qad.0b013e32828e4e27 . [DOI: 10.1097/qad.0b013e32828e4e27]
  54. Rom, S., Rom, I., Passiatore, G., Pacifici, M., Radhakrishnan, S., Del Valle, L., Piña-Oviedo, S., Khalili, K., Eletto, D., and Peruzzi, F. (2010). CCL8/MCP-2 is a target for mir-146a in HIV-1-infected human microglial cells. FASEB J. 24: 2292–2300, https://doi.org/10.1096/fj.09-143503 . [DOI: 10.1096/fj.09-143503]
  55. Roth, L.M., Zidane, B., Festa, L., Putatunda, R., Romer, M., Monnerie, H., Jordan-Sciutto, K.L., and Grinspan, J.B. (2021). Differential effects of integrase strand transfer inhibitors, elvitegravir and raltegravir, on oligodendrocyte maturation: a role for the integrated stress response. Glia 69: 362–376, https://doi.org/10.1002/glia.23902 . [DOI: 10.1002/glia.23902]
  56. Rourke, S.B., Bekele, T., Rachlis, A., Kovacs, C., Brunetta, J., Gill, M.J., Carvalhal, A., Cysique, L.A., Marcotte, T., and Power, C. (2021). Asymptomatic neurocognitive impairment is a risk for symptomatic decline over a 3-year study period. AIDS 35: 63–72, https://doi.org/10.1097/qad.0000000000002709 . [DOI: 10.1097/qad.0000000000002709]
  57. Saiyed, Z.M., Gandhi, N., Agudelo, M., Napuri, J., Samikkannu, T., Reddy, P.V.B., Khatavkar, P., Yndart, A., Saxena, S.K., and Nair, M.P.N. (2011). HIV-1 Tat upregulates expression of histone deacetylase-2 (HDAC2) in human neurons: implication for HIV-associated neurocognitive disorder (HAND). Neurochem. Int. 58: 656–664, https://doi.org/10.1016/j.neuint.2011.02.004 . [DOI: 10.1016/j.neuint.2011.02.004]
  58. Samboju, V., Philippi, C.L., Chan, P., Cobigo, Y., Fletcher, J.L.K., Robb, M., Hellmuth, J., Benjapornpong, K., Dumrongpisutikul, N., Pothisri, M., et al.. (2018). Structural and functional brain imaging in acute HIV. Neuroimage. Clin. 20: 327–335, https://doi.org/10.1016/j.nicl.2018.07.024 . [DOI: 10.1016/j.nicl.2018.07.024]
  59. Shah, A. and Kumar, A. (2010). HIV-1 gp120-mediated increases in IL-8 production in astrocytes are mediated through the NF-κB pathway and can be silenced by gp120-specific siRNA. J. Neuroinflammation 7: 96, https://doi.org/10.1186/1742-2094-7-96 . [DOI: 10.1186/1742-2094-7-96]
  60. Song, B., Li, Y., Liu, J., Mi, H., Liu, D., Wang, W., Sun, J., Wang, Y., and Li, H. (2020). A longitudinal study of brain volume changes in rhesus macaque model infected with SIV. J. Neurovirol. 26: 581–589, https://doi.org/10.1007/s13365-020-00864-x . [DOI: 10.1007/s13365-020-00864-x]
  61. Sun, J., Li, H., Liu, J., Zhao, J., Yuan, D., Guo, J., Li, L., Ding, J., and Li, R. (2019). The DTI changes and peripheral blood test results corroborate the early brain damage of SIV-infected rhesus. Radiol. Infect.Dis. 6: 8–14, https://doi.org/10.1016/j.jrid.2019.01.001 . [DOI: 10.1016/j.jrid.2019.01.001]
  62. Thames, A.D., Briones, M.S., Magpantay, L.I., Martinez-Maza, O., Singer, E.J., Hinkin, C.H., Morgello, S., Gelman, B.B., Moore, D.J., Heizerling, K., et al.. (2015). The role of chemokine C-C motif ligand 2 genotype and cerebrospinal fluid chemokine C-C motif ligand 2 in neurocognition among HIV-infected patients. AIDS 29: 1483–1491, https://doi.org/10.1097/qad.0000000000000706 . [DOI: 10.1097/qad.0000000000000706]
  63. Ubaida-Mohien, C., Lamberty, B., Dickens, A.M., Mielke, M.M., Marcotte, T., Sacktor, N., Grant, I., Letendre, S., Franklin, D., Cibrowski, P., et al.. (2017). Modifications in acute phase and complement systems predict shifts in cognitive status of HIV-infected patients. AIDS 31: 1365–1378, https://doi.org/10.1097/qad.0000000000001503 . [DOI: 10.1097/qad.0000000000001503]
  64. Ulfhammer, G., Edén, A., Antinori, A., Brew, B.J., Calcagno, A., Cinque, P., De Zan, V., Hagberg, L., Lin, A., Nilsson, S., et al.. (2022). Cerebrospinal fluid viral load across the spectrum of untreated human immunodeficiency virus type 1 (HIV-1) infection: a cross-sectional multicenter study. Clin. Infect. Dis. 75: 493–502, https://doi.org/10.1093/cid/ciab943 . [DOI: 10.1093/cid/ciab943]
  65. Underwood, J., Cole, J.H., Caan, M., De Francesco, D., Leech, R., van Zoest, R.A., Su, T., Geurtsen, G.J., Schmand, B.A., Portegies, P., et al.. (2017). Gray and white matter abnormalities in treated human immunodeficiency virus disease and their relationship to cognitive function. Clin. Infect. Dis. 65: 422–432, https://doi.org/10.1093/cid/cix301 . [DOI: 10.1093/cid/cix301]
  66. Vaidya, S.A., Korner, C., Sirignano, M.N., Amero, M., Bazner, S., Rychert, J., Allen, T.M., Rosenberg, E.S., Bosch, R.J., and Altfeld, M. (2014). Tumor necrosis factor α is associated with viral control and early disease progression in patients with HIV type 1 infection. J. Infect. Dis. 210: 1042–1046, https://doi.org/10.1093/infdis/jiu206 . [DOI: 10.1093/infdis/jiu206]
  67. Valcour, V., Chalermchai, T., Sailasuta, N., Marovich, M., Lerdlum, S., Suttichom, D., Suwanwela, N.C., Jagodzinski, L., Michael, N., Spudich, S., et al.. (2012). Central nervous system viral invasion and inflammation during acute HIV infection. J. Infect. Dis. 206: 275–282, https://doi.org/10.1093/infdis/jis326 . [DOI: 10.1093/infdis/jis326]
  68. Vera, J.H., Bracchi, M., Alagaratnam, J., Lwanga, J., Fox, J., Winston, A., Boffito, M., and Nelson, M. (2019). Improved central nervous system symptoms in people with HIV without objective neuropsychiatric complaints switching from efavirenz to rilpivirine containing cART. Brain. Sci. 9: 195, https://doi.org/10.3390/brainsci9080195 . [DOI: 10.3390/brainsci9080195]
  69. Vera, J.H., Guo, Q., Cole, J.H., Boasso, A., Greathead, L., Kelleher, P., Rabiner, E.A., Kalk, N., Bishop, C., Gunn, R.N., et al.. (2016). Neuroinflammation in treated HIV-positive individuals: a TSPO PET study. Neurology 86: 1425–1432, https://doi.org/10.1212/wnl.0000000000002485 . [DOI: 10.1212/wnl.0000000000002485]
  70. Wang, Z., Zheng, Y., Liu, L., Shen, Y., Zhang, R., Wang, J., and Lu, H. (2013). High prevalence of HIV-associated neurocognitive disorder in HIV-infected patients with a baseline CD4 count ≤ 350 cells/μL in Shanghai. China. Biosci. Trends. 7: 284–289.
  71. Weber, M.T., Finkelstein, A., Uddin, M.N., Reddy, E.A., Arduino, R.C., Wang, L., Tivarus, M.E., Zhong, J., Qiu, X., and Schifitto, G. (2022). Longitudinal effects of combination antiretroviral therapy on cognition and neuroimaging biomarkers in treatment-naive people with HIV. Neurology 99: e1045–e1055, https://doi.org/10.1212/wnl.0000000000200829 . [DOI: 10.1212/wnl.0000000000200829]
  72. Wei, J., Hou, J., Mu, T., Sun, J., Li, S., Wu, H., Su, B., and Zhang, T. (2022). Evaluation of computerized cognitive training and cognitive and daily function in patients living with HIV: a meta-analysis. JAMA. Netw. Open 5: e220970, https://doi.org/10.1001/jamanetworkopen.2022.0970 . [DOI: 10.1001/jamanetworkopen.2022.0970]
  73. Weiler, M., Stieger, K.C., Long, J.M., and Rapp, P.R. (2020). Transcranial magnetic stimulation in Alzheimer’s disease: are we ready? Eneuro 7: ENEURO.0235-19.2019, https://doi.org/10.1523/eneuro.0235-19.2019 . [DOI: 10.1523/eneuro.0235-19.2019]
  74. Wiederin, J., Rozek, W., Duan, F., and Ciborowski, P. (2009). Biomarkers of HIV-1 associated dementia: proteomic investigation of sera. Proteome. Sci. 7: 8, https://doi.org/10.1186/1477-5956-7-8 . [DOI: 10.1186/1477-5956-7-8]
  75. Xu, Y., Lin, Y., Bell, R.P., Towe, S.L., Pearson, J.M., Nadeem, T., Chan, C., and Meade, C.S. (2021). Machine learning prediction of neurocognitive impairment among people with HIV using clinical and multimodal magnetic resonance imaging data. J. Neurovirol. 27: 1–11, https://doi.org/10.1007/s13365-020-00930-4 . [DOI: 10.1007/s13365-020-00930-4]
  76. Xu, Z., Asahchop, E.L., Branton, W.G., Gelman, B.B., Power, C., and Hobman, T.C. (2017). MicroRNAs upregulated during HIV infection target peroxisome biogenesis factors: implications for virus biology, disease mechanisms and neuropathology. PLoS Pathog. 13: e1006360, https://doi.org/10.1371/journal.ppat.1006360 . [DOI: 10.1371/journal.ppat.1006360]
  77. Yang, X., Zhang, J., Cheng, Y., Cui, M., Jiang, Z., Fan, C., Chen, J., Qi, L., Liu, H., and Bao, D. (2023). Tenofovir disoproxil fumarate mediates neuronal injury by inducing neurotoxicity. Eur. J. Clin. Microbiol. Infect. Dis. 42: 1195–1205, https://doi.org/10.1007/s10096-023-04654-1 . [DOI: 10.1007/s10096-023-04654-1]
  78. Yelamanchili, S.V., Chaudhuri, A.D., Chen, L.-N., Xiong, H., and Fox, H.S. (2010). MicroRNA-21 dysregulates the expression of MEF2C in neurons in monkey and human SIV/HIV neurological disease. Cell Death Dis. 1: e77, https://doi.org/10.1038/cddis.2010.56 . [DOI: 10.1038/cddis.2010.56]
  79. Zeng, X.-F., Li, Q., Li, J., Wong, N., Li, Z., Huang, J., Yang, G., Sham, P.C., Li, S.-B., and Lu, G. (2018). HIV-1 Tat and methamphetamine co-induced oxidative cellular injury is mitigated by N-acetylcysteine amide (NACA) through rectifying mTOR signaling. Toxicol. Lett. 299: 159–171, https://doi.org/10.1016/j.toxlet.2018.09.009 . [DOI: 10.1016/j.toxlet.2018.09.009]
  80. Zhao, J., Jing, B., Chen, F., Liu, J., Wang, Y., and Li, H. (2017). Altered regional homogeneity of brain spontaneous signals in SIV infected rhesus macaque model. Magn. Reson. Imaging. 37: 56–61, https://doi.org/10.1016/j.mri.2016.10.019 . [DOI: 10.1016/j.mri.2016.10.019]
  81. Zhou, L., Diefenbach, E., Crossett, B., Tran, S.L., Ng, T., Rizos, H., Rua, R., Wang, B., Kapur, A., Gandhi, K., et al.. (2010). First evidence of overlaps between HIV-Associated Dementia (HAD) and non-viral neurodegenerative diseases: proteomic analysis of the frontal cortex from HIV+ patients with and without dementia. Mol. Neurodegener. 5: 27, https://doi.org/10.1186/1750-1326-5-27 . [DOI: 10.1186/1750-1326-5-27]
  82. Zhou, Y., Li, R., Wang, X., Miao, H., Wei, Y., Ali, R., Qiu, B., and Li, H. (2017). Motor-related brain abnormalities in HIV-infected patients: a multimodal MRI study. Neuroradiology 59: 1133–1142, https://doi.org/10.1007/s00234-017-1912-1 . [DOI: 10.1007/s00234-017-1912-1]
Journal Article Review

Word Cloud

Created with Highcharts 10.0.0neurocognitiveHANDstrategiesHIVneuroimaginginfectionalongsidemanagementearlydiagnosisartificialintelligencetreatmentHIV-associateddisordersDespitesignificantprogressmanagingHIV -associateddisordercontinuesconcernevenamongindividualswell -controlledCurrentdiagnosticprimarilyreliantneuropsychologicaltestsbiomarkersbloodcerebrospinalfluidcombinationantiretroviraltherapyformfoundationHoweveroftenfailidentifymildparticularlyasymptomaticimpairmentresultingdelayedinterventionFurthermoreinabilityperformin-depthmolecularanalysesconductlongitudinaltrackinglimitstherapeuticadvancementsEmergingtechnologies -advancedmulti-omicssimianimmunodeficiencyvirusnon-humanprimatemodels -revolutionizingfieldinnovationsofferunprecedentedopportunitiesdeeperunderstandingdiseasemechanismdetectioncomprehensivemonitoringpersonalizedIntegratingcutting-edgetoolspromisesreshapelandscapeenhancingqualitylifelivingEvolvingSimianImmunodeficiencyVirusmultiomics

Similar Articles

Cited By