Altered mental status and allied cognitive disorders have devastating consequences for HIV-infected individuals and their caregivers. Neuropsychological deficits also have a negative impact on the quality of life.[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
These may arise as a direct effect of HIV infection: for example, as part of a spectrum of HIV-associated neurocognitive disorders (HAND) or as a psychiatric comorbidity (e.g., depression or alcohol/substance misuse). While HIV-related opportunistic infections and neoplasms may also present with progressive cognitive decline and personality changes, more often they manifest as an acute or subacute neurologic emergency. Patients are also at risk of ischemic stroke, and this should be considered in the setting of acute neurologic deterioration.
Early detection and treatment of HAND improves prognosis; poor performance in neuropsychological tests is associated with increased mortality.[2]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 central nervous system (CNS) opportunistic infections or tumors are important in reducing morbidity and mortality, although patients with CNS opportunistic infections may have a high prevalence of residual cognitive impairment.[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
In addition to decreasing the incidence of CNS opportunistic infections and prolonging survival, combination antiretroviral therapy (ART) has reduced the prevalence of the most severe form of HIV cognitive impairment (HIV-associated dementia [HAD]), and improved the quality of life of people living with HIV with cognitive problems.[4]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://www.doi.org/10.1212/WNL.0b013e318200d727
http://www.ncbi.nlm.nih.gov/pubmed/21135382?tool=bestpractice.com
[5]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
[6]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
[7]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
ART has also reduced the age-associated risk for HIV-associated dementia (HAD) and may improve psychiatric comorbidity, such as depression.[8]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
[9]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
[10]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 itself may occasionally result in altered mental status, either directly as a medication adverse event, or as a consequence of therapy-related immune reconstitution inflammatory syndrome.
Psychiatric comorbidity is highly prevalent in HIV-infected individuals. Depression is associated with low compliance with antiretroviral treatments and, potentially, with a more rapid disease progression.[11]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
[12]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.[13]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 therapy improves quality of life and treatment adherence, and decreases cognitive complaints.[14]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
[15]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
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.[16]National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association, and the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Sep 2023 [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
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National HIV/AIDS Clinicians' Consultation Center: guidelines
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European AIDS Clinical Society: guidelines
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Mind Exchange Working Group: assessment, diagnosis and treatment of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND)
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New York State Department of Health AIDS Institute: HIV infection in older adults
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