HIV-Associated Dementia: Pathogenesis, Risk Factors, Diagnosis, and Management – A Literature Review
DOI:
10.29303/jbt.v26i4.12950Published:
2026-08-25Downloads
Abstract
HIV-associated dementia (HAD) is the most severe form of HIV-associated neurocognitive disorders (HAND), characterized by significant cognitive impairment and decline in daily functioning. Despite the widespread use of antiretroviral therapy (ART), neurocognitive impairment remains an important clinical challenge among people living with HIV. This review aimed to summarize current evidence regarding the pathogenesis, diagnosis, risk factors, and management of HIV-associated dementia. The study was conducted using a literature review method by examining relevant scientific articles and publications discussing HIV-associated dementia and HIV-associated neurocognitive disorders. The findings indicate that HIV enters the central nervous system through the Trojan horse mechanism, infects microglia and macrophages, and induces chronic neuroinflammation, leading to neuronal damage and cognitive decline. Major risk factors include severe immunosuppression, advanced age, comorbidities, and social determinants. Diagnosis is established based on the Frascati criteria and supported by cognitive screening instruments. Antiretroviral therapy remains the cornerstone of treatment and may be complemented by cognitive rehabilitation and psychosocial support. In conclusion, HAD is a complex neurocognitive complication of HIV infection that continues to affect patients despite advances in ART. Early detection and multidisciplinary management are essential to preserve cognitive function and improve quality of life. Further studies are recommended to improve early screening strategies and develop more effective interventions for HIV-associated cognitive impairment.
Keywords:
Antiretroviral therapy, Cognitive impairment, HIV-associated dementia, HIV-associated neurocognitive disorders, NeuroinflammationReferences
Boonyagars, L., Kiatsoongsong, N., & Winitprichagul, S. (2022). HIV-associated dementia: Associated factors and characteristics of cognitive domain abnormalities in elderly people living with HIV treated with highly active antiretroviral therapy. The American Journal of Tropical Medicine and Hygiene, 107(6), 1250–1257. https://doi.org/10.4269/ajtmh.22-0234
Cornea, A., Lata, I., Simu, M., & Rosca, E. C. (2023). Assessment and diagnosis of HIV-associated dementia. Viruses, 15(2), 378. https://doi.org/10.3390/v15020378
Davis, K., Grant, K.-G., Sousou, J. M., & Ilechukwu, S. (2025). Ethical and clinical considerations in the workup of HIV-associated neurocognitive decline. Cureus, 17(11), e97348. https://doi.org/10.7759/cureus.97348
Elendu, C., Aguocha, C. M., Okeke, C. V., Okoro, C. B., & Peterson, J. C. (2023). HIV-related neurocognitive disorders: Diagnosis, treatment, and mental health implications: A review. Medicine, 102(43), e35652. https://doi.org/10.1097/MD.0000000000035652
Ellis, R. J., Marquine, M. J., Kaul, M., Fields, J. A., & Schlachetzki, J. C. M. (2023). Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management. Nature Reviews Neurology, 19(11), 668–687. https://doi.org/10.1038/s41582-023-00879-y
Filley, C. M., & Fields, R. D. (2016). White matter and cognition: Making the connection. Journal of Neurophysiology, 116(5), 2093–2104. https://doi.org/10.1152/jn.00221.2016
Gichane, M. W., Sullivan, K. A., Shayo, A. M., Mmbaga, B. T., O'Donnell, K., Cunningham, C. K., & Dow, D. E. (2018). Caregiver role in HIV medication adherence among HIV-infected orphans in Tanzania. AIDS Care, 30(6), 701–705. https://doi.org/10.1080/09540121.2017.1391986
Henderson, M., & Winston, A. (2025). Risk factors for cognitive decline in persons with HIV. Current Opinion in Infectious Diseases, 38(1), 37–43. https://doi.org/10.1097/QCO.0000000000001080
Kami-Onaga, K., Tateyama, M., Kinjo, T., Parrott, G., Tominaga, D., Takahashi-Nakazato, A., Nakamura, H., Tasato, D., Miyagi, K., Maeda, S., Arae, H., Uehara, H., Miyagi, K., Haranaga, S., & Fujita, J. (2018). Comparison of two screening tests for HIV-associated neurocognitive disorder in suspected Japanese patients with respect to cART usage. PLOS ONE, 13(6), e0199106. https://doi.org/10.1371/journal.pone.0199106
Kelebie, M. A., Tinsae, T., Alemayehu, B. F., Walelign, G. K., & Takelle, G. M. (2024). Prevalence and associated factors of neurocognitive disorder among people living with HIV/AIDS in the South Gondar Zone primary hospitals, North-West Ethiopia: An institution-based cross-sectional study. BMJ Open, 14, e082773. https://doi.org/10.1136/bmjopen-2023-082773
Kellett-Wright, J., Flatt, A., Eaton, P., Urasa, S., Howlett, W., Dekker, M., Kisoli, A., Duijnmaijer, A., Thornton, J., McCartney, J., Yarwood, V., Irwin, C., Mukaetova-Ladinska, E., Akinyemi, R., Lwezuala, B., Gray, W. K., Walker, R. W., Dotchin, C. L., Makupa, P., & Paddick, S. M. (2021). Screening for HIV-associated neurocognitive disorder (HAND) in adults aged 50 and over attending a government HIV clinic in Kilimanjaro, Tanzania: Comparison of the International HIV Dementia Scale (IHDS) and IDEA Six Item Dementia Screen. AIDS and Behavior, 25, 542–553. https://doi.org/10.1007/s10461-020-02998-9
Mitra, P., & Sharman, T. (2024). HIV-associated neurocognitive disorder. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK555954/
Mustafa, M., Musselman, D., Jayaweera, D., da Fonseca Ferreira, A., Marzouka, G., & Dong, C. (2024). HIV-associated neurocognitive disorder (HAND) and Alzheimer's disease pathogenesis: Future directions for diagnosis and treatment. International Journal of Molecular Sciences, 25(20), 11170. https://doi.org/10.3390/ijms252011170
Nightingale, S., Ances, B., Cinque, P., Dravid, A., Dreyer, A. J., Gisslén, M., Joska, J. A., Kwasa, J., Meyer, A. C., Mpongo, N., Nakasujja, N., Pebody, R., Pozniak, A., Price, R. W., Sandford, C., Saylor, D., Thomas, K. G. F., Underwood, J., Vera, J. H., & Winston, A. (2023). Cognitive impairment in people living with HIV: Consensus recommendations for a new approach. Nature Reviews Neurology, 19(7), 424–433. https://doi.org/10.1038/s41582-023-00813-2
Osborne, O., Peyravian, N., Nair, M., Daunert, S., & Toborek, M. (2020). The paradox of HIV blood-brain barrier penetrance and antiretroviral drug delivery deficiencies. Trends in Neurosciences, 43(9), 695–708. https://doi.org/10.1016/j.tins.2020.06.007
Panel on Antiretroviral Guidelines for Adults and Adolescents. (2023). Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. U.S. Department of Health and Human Services. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv
Rosca, E. C., Tadger, P., Cornea, A., Tudor, R., Oancea, C., & Simu, M. (2021). International HIV Dementia Scale for HIV-associated neurocognitive disorders: A systematic review and meta-analysis. Diagnostics, 11(6), 1124. https://doi.org/10.3390/diagnostics11061124
Thompson, L. J.-P., Genovese, J., Hong, Z., Singh, M. V., & Singh, V. B. (2024). HIV-associated neurocognitive disorder: A look into cellular and molecular pathology. International Journal of Molecular Sciences, 25(9), 4697. https://doi.org/10.3390/ijms25094697
Vastag, Z., Fira-Mladinescu, O., & Rosca, E. C. (2022). HIV-associated neurocognitive disorder (HAND): Obstacles to early neuropsychological diagnosis. International Journal of General Medicine, 15, 4079–4090. https://doi.org/10.2147/IJGM.S295859
Weber, E., Blackstone, K., & Woods, S. P. (2013). Cognitive neurorehabilitation of HIV-associated neurocognitive disorders: A qualitative review and call to action. Neuropsychology Review, 23(1), 81–98. https://doi.org/10.1007/s11065-013-9225-6
World Health Organization. (2021). Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: Recommendations for a public health approach. World Health Organization. https://www.who.int/publications/i/item/9789240031593
Zhou, Z., Wang, W., Li, H., Shi, Y., Zhao, L., Lu, Y., Wei, X., & Li, H. (2025). Decoding HIV-associated neurocognitive disorders: A new perspective from multimodal connectomics. Frontiers in Neurology, 16, 1467175. https://doi.org/10.3389/fneur.2025.1467175
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