HIV-Associated Dementia: Current Diagnostic Challenges and Implications for Comprehensive Care. A Narrative Review

HIV-Associated Dementia: Current Diagnostic Challenges and Implications for Comprehensive Care. A Narrative Review

Main Article Content

Alfredo Duvergel Moreira
https://orcid.org/0000-0001-8996-0486
Juan Carlos de la Cruz González
https://orcid.org/0009-0006-1500-3011
Mohamed Azis Pérez-Caldevilla
https://orcid.org/0000-0001-8920-5261

Abstract

Introduction: HIV-associated dementia (HAD) has become less frequent in the antiretroviral therapy era, but its diagnosis and management pose new challenges because of aging, multimorbidity, and the diverse causes of cognitive impairment among people with HIV. Objective: To characterize HAD in the current context, considering its clinical, neurocognitive, and psychosocial features, as well as current diagnostic challenges and implications for comprehensive care. Methods: The review followed SANRA criteria. Searches were conducted from April to August 2026 in PubMed/MEDLINE, Scopus, Web of Science, and Embase, primarily covering publications from January 2022 to August 2026; 30 publications were included in the synthesis. Results: The evidence indicates a decline in severe forms of HIV-related neurocognitive impairment, alongside increasing complexity in attributing dementia specifically to HIV. The Frascati criteria remain an important research framework, although their limitations have prompted contemporary approaches that place greater emphasis on clinical course, functional impairment, and differentiation from alternative etiologies. Brief cognitive screening tools cannot replace comprehensive neuropsychological, functional, and etiological assessment. Care should integrate virological control, management of comorbidities, mental health care, rehabilitation, and family and social support through interdisciplinary coordination. Evidence specifically focused on HAD remains limited compared with the broader literature on neurocognitive impairment and is characterized by diagnostic and geographical heterogeneity. Conclusions: Although HAD is less frequent today, its recognition and management require individualized, multidimensional, and interdisciplinary assessment and care.


 

References

[1] Cysique LA, Levin J, Howard C, Taylor J, Rule J, Costello J, et al. Fostering healthy cognitive ageing in people living with HIV. Lancet HIV. 2025;12(1):e71-e80. DOI: https://doi.org/10.1016/S2352-3018(24)00248-0

[2] Nolasco M, Pokala SS, Saavedra Forero LM, Cuevas J, Koble JM, Conklin JL, et al. Risk factors for HIV-associated neurocognitive impairment and frailty in aging people with HIV in Latin America: a systematic review. BMC Neurol. 2026;26:312. DOI: https://doi.org/10.1186/s12883-026-04767-y

[3] Mastrorosa I, Pinnetti C, Brita AC, Mondi A, Lorenzini P, Del Duca G, et al. Declining prevalence of human immunodeficiency virus (HIV)-associated neurocognitive disorders in recent years and associated factors in a large cohort of antiretroviral therapy-treated individuals with HIV. Clin Infect Dis. 2023;76(3):e629-e637. DOI: https://doi.org/10.1093/cid/ciac658

[4] Lee E, Lee YG, Bang J. Risk factors associated with incident dementia in people living with HIV. J Korean Med Sci. 2025;40(22):e100. DOI: https://doi.org/10.3346/jkms.2025.40.e100

[5] Nightingale S, Ances B, Cinque P, Dravid A, Dreyer AJ, Gisslén M, et al. Cognitive impairment in people living with HIV: consensus recommendations for a new approach. Nat Rev Neurol. 2023;19(7):424-433. DOI: https://doi.org/10.1038/s41582-023-00813-2

[6] Baethge C, Goldbeck-Wood S, Mertens S. SANRA—a scale for the quality assessment of narrative review articles. Res Integr Peer Rev. 2019;4:5. DOI: https://doi.org/10.1186/s41073-019-0064-8

[7] Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69(18):1789-1799. DOI: https://doi.org/10.1212/01.WNL.0000287431.88658.8b

[8] Wang Y, Liu M, Lu Q, Farrell M, Lappin JM, Shi J, et al. Global prevalence and burden of HIV-associated neurocognitive disorder: a meta-analysis. Neurology. 2020;95(19):e2610-e2621. DOI: https://doi.org/10.1212/WNL.0000000000010752

[9] Ru W, Tang SJ. HIV-associated synaptic degeneration. Mol Brain. 2017;10(1):40. DOI: https://doi.org/10.1186/s13041-017-0321-z

[10] Cornea A, Lata I, Simu M, Rosca EC. Assessment and diagnosis of HIV-associated dementia. Viruses. 2023;15(2):378. DOI: https://doi.org/10.3390/v15020378

[11] Weber MT, Finkelstein A, Uddin MN, Reddy EA, Arduino RC, Wang L, et al. Longitudinal effects of combination antiretroviral therapy on cognition and neuroimaging biomarkers in treatment-naive people with HIV. Neurology. 2022;99(10):e1045-e1055. DOI: https://doi.org/10.1212/WNL.0000000000200829

[12] Henderson M, Winston A. Risk factors for cognitive decline in persons with HIV. Curr Opin Infect Dis. 2025;38(1):37-43. DOI: https://doi.org/10.1097/QCO.0000000000001080

[13] Ellis RJ, Paolillo EW, Saloner R, Heaton RK. Higher comorbidity burden predicts worsening neurocognitive trajectories in people with human immunodeficiency virus. Clin Infect Dis. 2022;74(8):1323-1328. DOI: https://doi.org/10.1093/cid/ciab655

[14] Lam JO, Hou CE, Gilsanz P, Lee C, Lea AN, Satre DD, et al. Undiagnosed cognitive impairment and impact on instrumental activities of daily living among people with HIV infection in primary care. Open Forum Infect Dis. 2023;10(6):ofad284. DOI: https://doi.org/10.1093/ofid/ofad284

[15] Zipursky AR, Gogolishvili D, Rueda S, Brunetta J, Carvalhal A, McCombe JA, et al. Evaluation of brief screening tools for neurocognitive impairment in HIV/AIDS: a systematic review of the literature. AIDS. 2013;27(15):2385-2401. DOI: https://doi.org/10.1097/QAD.0b013e328363bf56

[16] Kelly CM, Nightingale S, Gupta RK, Collier DA. HIV cerebrospinal fluid escape: interventions for the management, current evidence and future perspectives. Trop Med Infect Dis. 2025;10(2):45. DOI: https://doi.org/10.3390/tropicalmed10020045

[17] Alford K, Banerjee S, Daley S, Hamlyn E, Trotman D, Vera JH. Health-related quality of life in people living with HIV with cognitive symptoms: assessing relevant domains and associations. J Int Assoc Provid AIDS Care. 2023;22:23259582231164241. DOI: https://doi.org/10.1177/23259582231164241

[18] Wang CX, Chentsova VO, Prescott MR, Umlauf A, Moore DJ, Ellis RJ, et al. Independent and combined adverse effects of neurocognitive impairment and depression on everyday functioning and quality of life in people with HIV. J Int Neuropsychol Soc. 2025;31(2):147-156. DOI: https://doi.org/10.1017/S1355617725000153

[19] Britton MK, Lembo M, Li Y, Porges EC, Cook RL, Cohen RA, et al. HIV stigma is associated with two-year decline in cognitive performance among people with HIV. AIDS Behav. 2025;29(1):90-100. DOI: https://doi.org/10.1007/s10461-024-04508-7

[20] Yoo-Jeong M, Nguyen AL. Combined effects of social isolation and loneliness on patient-reported outcomes in older adults with HIV. AIDS Care. 2024;36(9):1325-1332. DOI: https://doi.org/10.1080/09540121.2024.2339046

[21] Yoo-Jeong M, Dastgheyb RM, Shorer EF, Demsky C, Fox O, Inaganti D, et al. Emotional loneliness is related to objective cognitive function in older people with HIV in the Washington-Baltimore area: a cross-sectional study. J Assoc Nurses AIDS Care. 2024;35(6):519-529. DOI: https://doi.org/10.1097/JNC.0000000000000491

[22] Gervolino SC, Krause KD, Halkitis PN. The role of social support networks in a sample of older adults living with HIV: the GOLD studies. AIDS Care. 2024;36(9):1302-1309. DOI: https://doi.org/10.1080/09540121.2024.2312877

[23] Damas J, Darling KEA, Bidlingmeyer P, Nadin-Debluë I, Bieler M, Vollino L, et al. One for all, all for one: neuro-HIV multidisciplinary platform for the assessment and management of neurocognitive complaints in people living with HIV. HIV Med. 2023;24(6):738-748. DOI: https://doi.org/10.1111/hiv.13472

[24] Fischer EL, Renaud A, Grivaz P, Di Liberto G, Ryvlin P, Cavassini M, et al. Advances in assessment and cognitive neurorehabilitation of HIV-related neurocognitive impairment. Brain Commun. 2025;7(1):fcae399. DOI: https://doi.org/10.1093/braincomms/fcae399

[25] Desai R, Vera J, Barber T, Alford K, Tanner C, Kothari K, et al. Effectiveness of interventions on cognitive decline risk for people living with HIV on antiretroviral therapy: a systematic review. Lancet Healthy Longev. 2026;7(4):100849. DOI: https://doi.org/10.1016/j.lanhl.2026.100849

[26] Stuart L, Alford K, Vera JH. Non-pharmaceutical interventions for people living with HIV with cognitive impairment: A scoping review. PLoS One. 2024;19(11):e0314185. DOI: https://doi.org/10.1371/journal.pone.0314185

[27] Moschopoulos CD, Alford K, Antoniadou A, Vera JH. Cognitive impairment in people living with HIV: mechanisms, controversies, and future perspectives. Trends Mol Med. 2024;30(11):1076-1089. DOI: https://doi.org/10.1016/j.molmed.2024.06.005

[28] Heaton RK, Ellis RJ, Tang B, Marra CM, Rubin LH, Clifford DB, et al. Twelve-year neurocognitive decline in HIV is associated with comorbidities, not age: a CHARTER study. Brain. 2023;146(3):1121-1131. DOI: https://doi.org/10.1093/brain/awac465

[29] Aung HL, Bloch M, Vincent T, Mao L, Brew BJ, Cysique LA. Low incidence of advanced neurological burden but high incidence of age-related conditions that are dementia risk factors in aging people living with HIV: a data-linkage 10-year follow-up study. J Neurovirol. 2023;29(2):141-155. DOI: https://doi.org/10.1007/s13365-022-01104-0

[30] Ostermann PN, Evering TH. The impact of aging on HIV-1-related neurocognitive impairment. Ageing Res Rev. 2024;102:102513. DOI: https://doi.org/10.1016/j.arr.2024.102513

[31] Mustafa M, Musselman D, Jayaweera D, da Fonseca Ferreira A, Marzouka G, Dong C. HIV-associated neurocognitive disorder (HAND) and Alzheimer’s disease pathogenesis: future directions for diagnosis and treatment. Int J Mol Sci. 2024;25(20):11170. DOI: https://doi.org/10.3390/ijms252011170

Similar Articles

You may also start an advanced similarity search for this article.