Evaluation of HIV-related mental status changes

HIV-related mental status changes and associated cognitive disorders have profound consequences for people living with HIV, and their caregivers.

Neuropsychologic deficits have a negative impact on the quality of life of people living with HIV, and are associated with increased risk of mortality.[1]Pandya R, Krentz HB, Gill MJ, et al. HIV-related neurological syndromes reduce health-related quality of life. Can J Neurol Sci. 2005 May;32(2):201-4. http://www.ncbi.nlm.nih.gov/pubmed/16018155?tool=bestpractice.com [2]Banerjee N, McIntosh RC, Ironson G. Impaired neurocognitive performance and mortality in HIV: assessing the prognostic value of the HIV-dementia scale. AIDS Behav. 2019 Dec;23(12):3482-92. https://pmc.ncbi.nlm.nih.gov/articles/PMC6713617 http://www.ncbi.nlm.nih.gov/pubmed/30820848?tool=bestpractice.com ​​ Neuropsychologic deficit may arise as a direct effect of HIV infection, for example, as part of the spectrum of HIV-associated neurocognitive disorders (HAND), or as a psychiatric comorbidity (e.g., depression or alcohol/substance misuse). 

Central nervous system (CNS) HIV-related opportunistic infections and neoplasms may present, acutely or subacutely, with progressive cognitive decline and personality changes. Patients with CNS opportunistic infections, such as CNS toxoplasmosis, may have a high prevalence of residual cognitive impairment (up to seven years following CNS opportunistic infection recovery).[3]Levine AJ, Hinkin CH, Ando K, et al. An exploratory study of long-term neurocognitive outcomes following recovery from opportunistic brain infections in HIV+ adults. J Clin Exp Neuropsychol. 2008 Oct;30(7):836-43. http://www.ncbi.nlm.nih.gov/pubmed/18608693?tool=bestpractice.com [4]Diaz MM, McCutchan JA, Crescini M, et al. Longitudinal study of cognitive function in people with HIV and toxoplasmic encephalitis or latent toxoplasma infection. AIDS. 2024 Dec 1;38(15):2021-9. http://www.ncbi.nlm.nih.gov/pubmed/39120536?tool=bestpractice.com

People living with HIV are at higher risk of ischemic stroke compared with people without HIV due to more rapid atherosclerosis and neurovascular inflammation.[5]Paternò Raddusa MS, Marino A, Celesia BM, et al. Atherosclerosis and cardiovascular complications in people living with HIV: a focused review. Infect Dis Rep. 2024 Sep 1;16(5):846-63. https://www.mdpi.com/2036-7449/16/5/66 http://www.ncbi.nlm.nih.gov/pubmed/39311207?tool=bestpractice.com ​ Stroke should, therefore, be considered in any person living with HIV who presents with acute neurologic deterioration.[6]Chow FC, Regan S, Zanni MV, et al. Elevated ischemic stroke risk among women living with HIV infection. AIDS. 2018 Jan 2;32(1):59-67. https://pmc.ncbi.nlm.nih.gov/articles/PMC5718937 http://www.ncbi.nlm.nih.gov/pubmed/28926405?tool=bestpractice.com

Psychiatric comorbidities are highly prevalent among people living with HIV. Depression is associated with nonadherence or partial adherence with antiretroviral therapy (ART), potentially leading to more rapid disease progression.[7]Lima VD, Geller J, Bangsberg DR, et al. The effect of adherence on the association between depressive symptoms and mortality among HIV-infected individuals first initiating HAART. AIDS. 2007 May 31;21(9):1175-83. http://www.ncbi.nlm.nih.gov/pubmed/17502728?tool=bestpractice.com [8]Leserman J. HIV disease progression: depression, stress, and possible mechanisms. Biol Psychiatry. 2003 Aug 1;54(3):295-306. http://www.ncbi.nlm.nih.gov/pubmed/12893105?tool=bestpractice.com ​​ Patients who are depressed, have anxiety, or have a substance use disorder at the time of initiating ART have a poorer virologic response to treatment.[9]Pence BW, Miller WC, Gaynes BN, et al. Psychiatric illness and virologic response in patients initiating highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2007 Feb 1;44(2):159-66. http://www.ncbi.nlm.nih.gov/pubmed/17146374?tool=bestpractice.com ​ Effective antidepressant treatment improves quality of life and treatment adherence, and decreases cognitive complaints.[10]Elliott AJ, Russo J, Roy-Byrne PP. The effect of changes in depression on health related quality of life (HRQoL) in HIV infection. Gen Hosp Psychiatry. 2002 Jan-Feb;24(1):43-7. http://www.ncbi.nlm.nih.gov/pubmed/11814533?tool=bestpractice.com [11]Claypoole KH, Elliott AJ, Uldall KK, et al. Cognitive functions and complaints in HIV-1 individuals treated for depression. Appl Neuropsychol. 1998;5(2):74-84. http://www.ncbi.nlm.nih.gov/pubmed/16318457?tool=bestpractice.com

ART reduces the incidence of CNS opportunistic infections, the prevalence of HIV-associated dementia (HAD; the most severe form of HIV neurocognitive impairment), and age-associated risk for HAD.[12]Heaton RK, Clifford DB, Franklin DR Jr, et al. HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology. 2010 Dec 7;75(23):2087-96. https://pmc.ncbi.nlm.nih.gov/articles/PMC2995535 http://www.ncbi.nlm.nih.gov/pubmed/21135382?tool=bestpractice.com [13]Gray F, Chrétien F, Vallat-Decouvelaere AV, et al. The changing pattern of HIV neuropathology in the HAART era. J Neuropathol Exp Neurol. 2003 May;62(5):429-40. http://www.ncbi.nlm.nih.gov/pubmed/12769183?tool=bestpractice.com [14]Antinori A, Arendt G, Becker JT, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007 Oct 30;69(18):1789-99. http://www.ncbi.nlm.nih.gov/pubmed/17914061?tool=bestpractice.com ​​ ART may improve the quality of life of people living with HIV with cognitive impairment and psychiatric comorbidity (such as depression).[15]Parsons TD, Braaten AJ, Hall CD, et al. Better quality of life with neuropsychological improvement on HAART. Health Qual Life Outcomes. 2006 Feb 24;4:11. http://www.hqlo.com/content/4/1/11 http://www.ncbi.nlm.nih.gov/pubmed/16504114?tool=bestpractice.com [16]Gibbie T, Mijch A, Ellen S, et al. Depression and neurocognitive performance in individuals with HIV/AIDS: 2-year follow-up. HIV Med. 2006 Mar;7(2):112-21. http://www.ncbi.nlm.nih.gov/pubmed/16420256?tool=bestpractice.com [17]Larussa D, Lorenzini P, Cingolani A, et al. Highly active antiretroviral therapy reduces the age-associated risk of dementia in a cohort of older HIV-1-infected patients. AIDS Res Hum Retroviruses. 2006 May;22(5):386-92. http://www.ncbi.nlm.nih.gov/pubmed/16706614?tool=bestpractice.com [18]Joska JA, Gouse H, Paul RH, et al. Does highly active antiretroviral therapy improve neurocognitive function? A systematic review. J Neurovirol. 2010 Mar;16(2):101-14. http://www.ncbi.nlm.nih.gov/pubmed/20345318?tool=bestpractice.com ​​ However, the use of ART may occasionally result in altered mental status, either directly as a drug adverse effect, or as a consequence of therapy-related immune reconstitution inflammatory syndrome (IRIS) of the CNS (a paradoxical deterioration in clinical status associated with rapid improvement in CD4 counts and a decrease in viral loads within the first few months after ART initiation).

Poor performance in neuropsychologic tests is associated with increased mortality.[19]Wilkie FL, Goodkin K, Eisdorfer C, et al. Mild cognitive impairment and risk of mortality in HIV-1 infection. J Neuropsychiatry Clin Neurosci. 1998 Spring;10(2):125-32. http://www.ncbi.nlm.nih.gov/pubmed/9608401?tool=bestpractice.com ​ Diagnosis and prompt treatment of CNS opportunistic infections or tumors can contribute to improved outcomes.[20]Sakai M, Higashi M, Fujiwara T, et al. MRI imaging features of HIV-related central nervous system diseases: diagnosis by pattern recognition in daily practice. Jpn J Radiol. 2021 Nov;39(11):1023-38. https://link.springer.com/article/10.1007/s11604-021-01150-4 http://www.ncbi.nlm.nih.gov/pubmed/34125369?tool=bestpractice.com ​ Early detection and treatment of HAND improves prognosis.[2]Banerjee N, McIntosh RC, Ironson G. Impaired neurocognitive performance and mortality in HIV: assessing the prognostic value of the HIV-dementia scale. AIDS Behav. 2019 Dec;23(12):3482-92. https://pmc.ncbi.nlm.nih.gov/articles/PMC6713617 http://www.ncbi.nlm.nih.gov/pubmed/30820848?tool=bestpractice.com [21]Elendu C, Aguocha CM, Okeke CV, et al. HIV-related neurocognitive disorders: diagnosis, treatment, and mental health implications: a review. Medicine (Baltimore). 2023 Oct 27;102(43):e35652. https://journals.lww.com/md-journal/fulltext/2023/10270/hiv_related_neurocognitive_disorders__diagnosis,.25.aspx http://www.ncbi.nlm.nih.gov/pubmed/37904369?tool=bestpractice.com

A number of resources are available that provide information on the assessment of neurologic manifestations in HIV infection, and specific guidance on the diagnosis and treatment of opportunistic infections.[22]National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association, and the Infectious Disease Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new

New York State Department of Health AIDS Institute: mental health screening Opens in new window

National HIV/AIDS Clinicians' Consultation Center: guidelines Opens in new window

European AIDS Clinical Society: guidelines Opens in new window

Mind Exchange Working Group: assessment, diagnosis and treatment of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) Opens in new window

New York State Department of Health AIDS Institute: HIV infection in older adults Opens in new window