Afecções associadas ao HIV
Inclui transtorno neurocognitivo associado ao HIV (TNAH), efeito adverso a medicamentos ou síndrome inflamatória da reconstituição imune (SIRI) relacionada à terapia.
Transtorno neurocognitivo associado ao HIV
Representa um espectro de comprometimento neurocognitivo progressivo que varia do comprometimento neurocognitivo assintomático (CNA) à demência associada ao HIV (DAH):[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
[23]Horberg M, Thompson M, Agwu A, et al. Primary care guidance for providers of care for persons with human immunodeficiency virus: 2024 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2024 Oct 12:ciae479.
https://www.doi.org/10.1093/cid/ciae479
http://www.ncbi.nlm.nih.gov/pubmed/39393187?tool=bestpractice.com
Por definição, essas condições só são diagnosticadas se o comprometimento não estiver ocorrendo como parte de um delirium secundário à infecção ou aos efeitos dos medicamentos, e não puderem ser explicadas por etiologias alternativas.[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
Efeito adverso do medicamento ou SIRI relacionada à terapia
A TAR pode induzir a problemas cognitivos ou psiquiátricos diretamente como um efeito adverso ou indiretamente através do seu efeito sobre o sistema imunológico. O efavirenz, um inibidor da transcriptase reversa não análogo de nucleosídeo (ITRNN), é associado ao desenvolvimento de efeitos adversos neuropsiquiátricos, especialmente nas primeiras semanas de tratamento.[24]Blanch J, Martínez E, Rousaud A, et al. Preliminary data of a prospective study on neuropsychiatric side effects after initiation of efavirenz. J Acquir Immune Defic Syndr. 2001 Aug 1;27(4):336-43.
http://www.ncbi.nlm.nih.gov/pubmed/11468421?tool=bestpractice.com
[25]Hawkins T, Geist C, Young B, et al. Comparison of neuropsychiatric side effects in an observational cohort of efavirenz- and protease inhibitor-treated patients. HIV Clin Trials. 2005 Jul-Aug;6(4):187-96.
http://www.ncbi.nlm.nih.gov/pubmed/16214735?tool=bestpractice.com
[26]Gazzard B, Balkin A, Hill A. Analysis of neuropsychiatric adverse events during clinical trials of efavirenz in antiretroviral-naive patients: a systematic review. AIDS Rev. 2010 Apr-Jun;12(2):67-75.
http://www.ncbi.nlm.nih.gov/pubmed/20571601?tool=bestpractice.com
[27]Cavalcante GI, Capistrano VL, Cavalcante FS, et al. Implications of efavirenz for neuropsychiatry: a review. Int J Neurosci. 2010 Dec;120(12):739-45.
http://www.ncbi.nlm.nih.gov/pubmed/20964556?tool=bestpractice.com
[28]Decloedt EH, Maartens G. Neuronal toxicity of efavirenz: a systematic review. Expert Opin Drug Saf. 2013 Nov;12(6):841-6.
http://www.ncbi.nlm.nih.gov/pubmed/23889591?tool=bestpractice.com
As taxas de efeitos adversos neuropsiquiátricos similares são significativamente menores com outros agentes do tipo ITRNN, como a nevirapina, etravirina, e rilpivirina.[29]Cohen CJ, Andrade-Villanueva J, Clotet B, et al; THRIVE Study Group. Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Lancet. 2011 Jul 16;378(9787):229-37.
http://www.ncbi.nlm.nih.gov/pubmed/21763935?tool=bestpractice.com
[30]Katlama C, Haubrich R, Lalezari J, et al; DUET-1, DUET-2 Study Groups. Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials. AIDS. 2009 Nov 13;23(17):2289-300.
http://www.ncbi.nlm.nih.gov/pubmed/19710593?tool=bestpractice.com
O inibidor da integrase raltegravir foi associado a efeitos adversos neuropsiquiátricos pouco frequentes, e dolutegravir pode estar associado à insônia e a outros efeitos sobre o sistema nervoso central (SNC).[31]Madeddu G, Menzaghi B, Ricci E, et al. Raltegravir central nervous system tolerability in clinical practice: results from a multicenter observational study. AIDS. 2012 Nov 28;26(18):2412-5.
http://www.ncbi.nlm.nih.gov/pubmed/23032413?tool=bestpractice.com
[32]Harris M, Larsen G, Montaner JG. Exacerbation of depression associated with starting raltegravir: a report of four cases. AIDS. 2008 Sep 12;22(14):1890-2.
http://www.ncbi.nlm.nih.gov/pubmed/18753871?tool=bestpractice.com
[33]Gray J, Young B. Acute onset insomnia associated with the initiation of raltegravir: a report of two cases and literature review. AIDS Patient Care STDs. 2009 Sep;23(9):689-90.
http://www.ncbi.nlm.nih.gov/pubmed/19663717?tool=bestpractice.com
[34]Walmsley SL, Antela A, Clumeck N, et al; SINGLE Investigators. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013 Nov 7;369(19):1807-18.
http://www.nejm.org/doi/full/10.1056/NEJMoa1215541#t=article
http://www.ncbi.nlm.nih.gov/pubmed/24195548?tool=bestpractice.com
[35]Lepik KJ, Yip B, Ulloa AC, et al. Adverse drug reactions to integrase strand transfer inhibitors. AIDS. 2018 Apr 24;32(7):903-12.
http://www.ncbi.nlm.nih.gov/pubmed/29424784?tool=bestpractice.com
[36]van den Berk G, Oryszczyn J, Blok W, et al. Unexpectedly high rate of intolerance for dolutegravir in real life setting. Poster 948 presented at CROI 2016. February 2016 [internet publication].
http://www.croiconference.org/sessions/unexpectedly-high-rate-intolerance-dolutegravir-real-life-setting
Pacientes que recebem TAR podem desenvolver SIRI como consequência da reação a agentes infecciosos de um sistema imunológico restaurado. Os agentes infecciosos comumente implicados incluem Mycobacterium tuberculosis ou complexo M avium, embora outras causas (por exemplo, vírus do herpes simples [HSV], vírus da varicela-zóster [VZV], leucoencefalopatia multifocal progressiva [poliomavírus humano 2, também conhecido como vírus John Cunningham [JCV]], citomegalovírus [CMV], infecção criptocócica e Toxoplasma gondii) também sejam fatores desencadeantes reconhecidos.[37]Torok ME, Kambugu A, Wright E. Immune reconstitution disease of the central nervous system. Curr Opin HIV AIDS. 2008 Jul;3(4):438-45.
http://www.ncbi.nlm.nih.gov/pubmed/19373003?tool=bestpractice.com
[38]Bicanic T, Meintjes G, Rebe K, et al. Immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis: a prospective study. J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):130-4.
http://www.ncbi.nlm.nih.gov/pubmed/19365271?tool=bestpractice.com
[39]McCombe JA, Auer RN, Maingat FG, et al. Neurologic immune reconstitution inflammatory syndrome in HIV/AIDS: outcome and epidemiology. Neurology. 2009 Mar 3;72(9):835-41.
http://www.ncbi.nlm.nih.gov/pubmed/19255411?tool=bestpractice.com
Afecções não associadas ao HIV
Abrange comorbidades sistêmicas e comorbidades psiquiátricas.
Comorbidades sistêmicas
A deficiência nutricional concomitante (por exemplo, folato, vitamina B12, vitamina D) pode causar comprometimento cognitivo, que pode ser observado no contexto de desnutrição em HIV/AIDS avançado.[40]The Mind Exchange Working Group. Assessment, diagnosis and treatment of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND): a consensus report of the Mind Exchange Program. Clin Infect Dis. 2013 Apr;56(7):1004-17.
http://www.ncbi.nlm.nih.gov/pubmed/23175555?tool=bestpractice.com
As pessoas com infecção por HIV avançada apresentam aumento do risco de AVC isquêmico em comparação com pessoas sem HIV.[41]Sico JJ, Chang CC, So-Armah K, et al; Veterans Aging Cohort Study. HIV status and the risk of ischemic stroke among men. Neurology. 2015 May 12;84(19):1933-40.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433456
http://www.ncbi.nlm.nih.gov/pubmed/25862803?tool=bestpractice.com
A patogênese subjacente varia e inclui êmbolos cerebrais secundários a doenças cardíacas, aterosclerose acelerada ou vasculite cerebral como consequência de sífilis ou uso de anfetamina/cocaína.
As pessoas que vivem com HIV e infecção concomitante por hepatite C apresentam maiores taxas de comprometimento cognitivo.[40]The Mind Exchange Working Group. Assessment, diagnosis and treatment of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND): a consensus report of the Mind Exchange Program. Clin Infect Dis. 2013 Apr;56(7):1004-17.
http://www.ncbi.nlm.nih.gov/pubmed/23175555?tool=bestpractice.com
[42]Hinkin CH, Castellon SA, Levine AJ, et al. Neurocognition in individuals co-infected with HIV and hepatitis C. J Addict Dis. 2008;27(2):11-7.
http://www.ncbi.nlm.nih.gov/pubmed/18681187?tool=bestpractice.com
A doença tireoidiana e o hipogonadismo são mais comuns em pessoas com HIV e podem representar uma causa subjacente de estado mental alterado.[40]The Mind Exchange Working Group. Assessment, diagnosis and treatment of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND): a consensus report of the Mind Exchange Program. Clin Infect Dis. 2013 Apr;56(7):1004-17.
http://www.ncbi.nlm.nih.gov/pubmed/23175555?tool=bestpractice.com
[43]Nelson M, Powles T, Zeitlin A, et al. Thyroid dysfunction and relationship to antiretroviral therapy in HIV-positive individuals in the HAART era. J Acquir Immune Defic Syndr. 2009 Jan 1;50(1):113-4.
http://www.ncbi.nlm.nih.gov/pubmed/19092451?tool=bestpractice.com
[44]Lortholary O, Christeff N, Casassus P, et al. Hypothalamo-pituitary-adrenal function in human immunodeficiency virus-infected men. J Clin Endocrinol Metab. 1996 Feb;81(2):791-6.
http://www.ncbi.nlm.nih.gov/pubmed/8636305?tool=bestpractice.com
[45]Mayo J, Collazos J, Martínez E, et al. Adrenal function in the human immunodeficiency virus-infected patient. Arch Intern Med. 2002 May 27;162(10):1095-8.
http://archinte.jamanetwork.com/article.aspx?articleid=211446
http://www.ncbi.nlm.nih.gov/pubmed/12020177?tool=bestpractice.com
Comorbidades psiquiátricas
As comorbidades psiquiátricas são altamente prevalentes em pessoas que vivem com HIV e podem contribuir para dificuldades cognitivas.[40]The Mind Exchange Working Group. Assessment, diagnosis and treatment of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND): a consensus report of the Mind Exchange Program. Clin Infect Dis. 2013 Apr;56(7):1004-17.
http://www.ncbi.nlm.nih.gov/pubmed/23175555?tool=bestpractice.com
Elas incluem:[23]Horberg M, Thompson M, Agwu A, et al. Primary care guidance for providers of care for persons with human immunodeficiency virus: 2024 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2024 Oct 12:ciae479.
https://www.doi.org/10.1093/cid/ciae479
http://www.ncbi.nlm.nih.gov/pubmed/39393187?tool=bestpractice.com
[40]The Mind Exchange Working Group. Assessment, diagnosis and treatment of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND): a consensus report of the Mind Exchange Program. Clin Infect Dis. 2013 Apr;56(7):1004-17.
http://www.ncbi.nlm.nih.gov/pubmed/23175555?tool=bestpractice.com
Depression
Ansiedade
Transtornos decorrentes do uso de bebidas alcoólicas e substâncias.
Comprometimento cognitivo devido à polimedicação de medicamentos prescritos, em particular aqueles com propriedades anticolinérgicas e medicamentos psicotrópicos