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OBJECTIVE: Although accumulating evidence implicating altered gut microbiota in human immunodeficiency virus (HIV) infection and neurodegenerative disorders; however, the association between dysbiosis of the gut microbiota and metabolites in the pathogenesis of HIV-associated neurocognitive disorder (HAND) remains unclear. METHODS: Fecal and plasma samples were obtained from 3 cohorts (HAND, HIV-non-HAND, and healthy controls), metagenomic analysis and metabolomic profiling were performed to investigate alterations in the gut microbial composition and circulating metabolites in HAND. RESULTS: The gut microbiota of people living with HIV (PLWH) had an increased relative abundance of Prevotella and a decreased relative abundance of Bacteroides. In contrast, Prevotella and Megamonas were substantially decreased, and Bacteroides and Phocaeicola were increased in HAND patients. Moreover, untargeted metabolomics identified several neurotransmitters and certain amino acids associated with neuromodulation, and the differential metabolic pathways of amino acids associated with neurocognition were depleted in HAND patients. Notably, most neuromodulatory metabolites are associated with an altered abundance of specific gut bacteria. INTERPRETATION: Our findings provide new insights into the intricate interplay between the gut and microbiome-brain axis in the pathogenesis of HAND, highlighting the potential for developing novel therapeutic strategies that specifically target the gut microbiota. ANN NEUROL 2024;96:306-320.
Assuntos
Aminoácidos , Microbioma Gastrointestinal , Metabolômica , Metagenômica , Humanos , Microbioma Gastrointestinal/fisiologia , Masculino , Pessoa de Meia-Idade , Feminino , Metabolômica/métodos , Aminoácidos/metabolismo , Aminoácidos/sangue , Adulto , Infecções por HIV/complicações , Complexo AIDS Demência/metabolismo , Complexo AIDS Demência/microbiologia , Fezes/microbiologia , DisbioseRESUMO
Since the identification of human immunodeficiency virus type 1 (HIV-1) in 1983, many improvements have been made to control viral replication in the peripheral blood and to treat opportunistic infections. This has increased life expectancy but also the incidence of age-related central nervous system (CNS) disorders and HIV-associated neurodegeneration/neurocognitive impairment and depression collectively referred to as HIV-associated neurocognitive disorders (HAND). HAND encompasses a spectrum of different clinical presentations ranging from milder forms such as asymptomatic neurocognitive impairment or mild neurocognitive disorder to a severe HIV-associated dementia (HAD). Although control of viral replication and suppression of plasma viral load with combination antiretroviral therapy has reduced the incidence of HAD, it has not reversed milder forms of HAND. The objective of this review, is to describe the mechanisms by which HIV-1 invades and disseminates in the CNS, a crucial event leading to HAND. The review will present the evidence that underlies the relationship between HIV infection and HAND. Additionally, recent findings explaining the role of neuroinflammation in the pathogenesis of HAND will be discussed, along with prospects for treatment and control.
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Complexo AIDS Demência , Doenças do Sistema Nervoso Central , Infecções por HIV , HIV-1 , Humanos , Infecções por HIV/epidemiologia , Doenças Neuroinflamatórias , Complexo AIDS Demência/tratamento farmacológico , Complexo AIDS Demência/epidemiologia , Complexo AIDS Demência/psicologia , Doenças do Sistema Nervoso Central/etiologia , Sistema Nervoso CentralRESUMO
Symptomatic HIV-associated neurocognitive disorder (HAND) is a complication of HIV (cognitive impairment, difficulties with everyday functioning). If detected early, interventions assist with optimizing care, avoiding rapid decline and enhancing coping. There remains inconsistency surrounding screening/diagnosis information within Australian healthcare professionals and community settings. A scoping review of academic literature, government policies and non-government organisations (NGOs) was conducted to map existing screening/diagnosis information using the guidelines of Joanna Briggs Institute. A literature search of EBSCOhost and Medline (dates: 2015-2021), the Australian government NGO web domains, Google and unpublished academic works was conducted (July 2021) and updated (December 2022) to identify Australian items (past 5 years). Seventeen items met the inclusion criteria. No government guidelines were identified. Various HIV-related organisations proposed different diagnostic guidelines. Most HAND research originated in Sydney. The most accessible information was from Dementia Australia, with some inaccuracies noted. There is scant Australian research/information on HAND screening/diagnosis. HAND translational research and screening/diagnosis standards are urgently needed to inform best practices. The Australian context is used to discuss international implications regarding higher-income countries with similar patterns/healthcare.
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Infecções por HIV , Programas de Rastreamento , Humanos , Austrália , Programas de Rastreamento/métodos , Infecções por HIV/diagnóstico , Infecções por HIV/complicações , Infecções por HIV/psicologia , Complexo AIDS Demência/diagnóstico , Transtornos Neurocognitivos/diagnóstico , Disfunção Cognitiva/diagnósticoRESUMO
Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with HIV continue to experience HIV-associated neurocognitive disorder (HAND). HAND is associated with neurocognitive impairment, including motor impairment, and memory loss. HIV has been detected in the brain within 8 days of estimated exposure and the mechanisms for this early entry are being actively studied. Once having entered into the central nervous system (CNS), HIV degrades the blood-brain barrier through the production of its gp120 and Tat proteins. These proteins are directly toxic to endothelial cells and neurons, and propagate inflammatory cytokines by the activation of immune cells and dysregulation of tight junction proteins. The BBB breakdown is associated with the progression of neurocognitive disease. One of the main hurdles for treatment for HAND is the latent pool of cells, which are insensitive to cART and prolong inflammation by harboring the provirus in long-lived cells that can reactivate, causing damage. Multiple strategies are being studied to combat the latent pool and HAND; however, clinically, these approaches have been insufficient and require further revisions. The goal of this paper is to aggregate the known mechanisms and challenges associated with HAND.
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Barreira Hematoencefálica , Humanos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Infecções por HIV/complicações , Infecções por HIV/virologia , Infecções por HIV/patologia , Infecções por HIV/metabolismo , Complexo AIDS Demência/metabolismo , Complexo AIDS Demência/patologia , HIV-1 , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/metabolismo , Transtornos Neurocognitivos/patologia , AnimaisRESUMO
OBJECTIVES: Blood-brain barrier impairment is frequent in people living with human immunodeficiency virus (PLWHIV), affecting the penetration of target cells and antiretrovirals into the central nervous system, through transporters (e.g. ABCB1), leading to neuroinflammation. This study aimed to identify variants of genes encoding transporters able to predict neuroinflammation biomarker levels. METHODS: Cerebrospinal fluid (CSF) and plasma samples were obtained from PLWHIV. The CSF biomarkers were quantified by commercial assays. Genetic variants were evaluated through real-time polymerase chain reaction (PCR). RESULTS: A total of 107 PLWHIV (163 samples) were included in the study: 79% were male, median age was 48.5 years, CD4% was 25%, and HIV-associated neurocognitive disorder (HAND) was observed in 17.8%. The ABCB1 2677G>T genetic variant showed a different allelic distribution according to the clinical group (P = 0.026). In linear regression analyses, HIV-related central nervous system disorders, ABCG2 1194+928CC genotype, log viral load, CSF-to-serum albumin ratio, ß-1,42 levels, and CSF proteins were retained in the final model as factors independently associated with CSF neopterin levels; CSF proteins and integrase inhibitor use were associated with CSF tau level in the multivariate model. Phospho-tau regression analysis reported the ABCB1 2677GT/TT genotype and CSF proteins as predictors in the final model; sex, protease inhibitors, neopterin, and ABCB1 2677 GT/ TT genotype were predictors in the multivariate regression for ß-1,42. CONCLUSIONS: For the first time, pharmacogenetic and clinical features were found to be predictors of neuro-inflammation biomarkers.
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Subfamília B de Transportador de Cassetes de Ligação de ATP , Biomarcadores , Infecções por HIV , Polimorfismo de Nucleotídeo Único , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/sangue , Infecções por HIV/complicações , Adulto , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Barreira Hematoencefálica , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Inflamação/líquido cefalorraquidiano , Carga Viral , Genótipo , Complexo AIDS Demência/líquido cefalorraquidiano , Complexo AIDS Demência/patologia , Complexo AIDS Demência/genética , Proteínas de NeoplasiasRESUMO
ABSTRACT: Speed of processing (SOP) cognitive training may improve indicators of the quality of life (QoL) in people living with HIV. In this 2-year, longitudinal, randomized, controlled trial, 216 participants ages 40 years and older with HIV-associated neurocognitive disorder or borderline HIV-associated neurocognitive disorder were assigned to one of three groups: (a) 10 hr of SOP training (n = 70); (b) 20 hr of SOP training (n = 73), or (c) 10 hr of internet navigation control training (a contact control group; n = 73). Participants completed several QoL measures at baseline, posttest, and Year 1 and Year 2 follow-ups. Using linear mixed-effect models, no strong pattern of training effects across QoL outcomes was apparent, with small-magnitude, nonsignificant, between-group differences in depression, locus of control, and Medical Outcomes Study-HIV scales. In conclusion, despite prior work showing some transfer of SOP cognitive training improving QoL, that was not observed. Implications for research and practice are posited.
Assuntos
Infecções por HIV , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Infecções por HIV/psicologia , Infecções por HIV/complicações , Adulto , Alabama , Estudos Longitudinais , Resultado do Tratamento , Terapia Cognitivo-Comportamental/métodos , Cognição , Depressão/psicologia , Transtornos Neurocognitivos , Complexo AIDS Demência/psicologia , Complexo AIDS Demência/terapia , Treino CognitivoRESUMO
HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP (p 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.
Assuntos
Infecções por HIV , Humanos , Feminino , Masculino , Tanzânia/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Idoso , Prevalência , Complexo AIDS Demência/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Transtornos Neurocognitivos/epidemiologia , Transtornos Neurocognitivos/etiologiaRESUMO
Although a significant amount of biomedical research has been conducted to study HIV-associated neurocognitive disorder (HAND), there has been scant research done to assess the awareness and knowledge of this public health concern among middle-aged and older people living with HIV/AIDS (PLWH). Our qualitative community-based participatory research study sought to address this research gap by examining the awareness and knowledge of HAND among relevant stakeholders in southern Nevada, USA. We conducted 15 semistructured interviews with middle-aged and older PLWH to examine their awareness and knowledge of HAND and access to pertinent resources. After our thematic analysis of our interviews, we identified two overarching themes: (1) limited awareness and knowledge of HAND among PLWH, and (2) southern Nevada social determinants of health. Our findings underscore the importance of raising awareness and knowledge of HAND among PLWH through community-based education programs, and improving access to resources related to social determinants of health.
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Pesquisa Participativa Baseada na Comunidade , Infecções por HIV , Conhecimentos, Atitudes e Prática em Saúde , Entrevistas como Assunto , Pesquisa Qualitativa , Determinantes Sociais da Saúde , Humanos , Feminino , Nevada , Pessoa de Meia-Idade , Masculino , Infecções por HIV/psicologia , Infecções por HIV/complicações , Idoso , Educação em Saúde/métodos , Transtornos Neurocognitivos/psicologia , Complexo AIDS Demência/psicologiaRESUMO
HIV infection is a multi-organ disease that involves the central nervous system (CNS). While devastating CNS complications such as HIV-associated dementia and CNS opportunistic infection typically manifest years after HIV acquisition, HIV RNA is readily detected in the cerebrospinal fluid in untreated neuroasymptomatic people with HIV, highlighting that HIV neuroinvasion predates overt clinical manifestations. Over the past two decades, increased awareness of HIV infection within the at-risk population, coupled with the accessibility of nucleic acid testing and modern HIV immunoassays, has made the detection of acute and early HIV infection readily achievable. This review aims to summarize research findings on CNS involvement during acute and early HIV infection, as well as the outcomes following the immediate initiation of antiretroviral therapy during this early stage of infection. The knowledge gap in long-term neuroprotection through early ART within the first year of infection will be discussed.
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Sistema Nervoso Central , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Sistema Nervoso Central/virologia , Sistema Nervoso Central/efeitos dos fármacos , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Complexo AIDS Demência/tratamento farmacológicoRESUMO
Our previous findings demonstrated that astrocytic HIF-1α plays a major role in HIV-1 Tat-mediated amyloidosis which can lead to Alzheimer's-like pathology-a comorbidity of HIV-Associated Neurocognitive Disorders (HAND). These amyloids can be shuttled in extracellular vesicles, and we sought to assess whether HIV-1 Tat stimulated astrocyte-derived EVs (ADEVs) containing the toxic amyloids could result in neuronal injury in vitro and in vivo. We thus hypothesized that blocking HIF-1α could likely mitigate HIV-1 Tat-ADEV-mediated neuronal injury. Rat hippocampal neurons when exposed to HIV-1 Tat-ADEVs carrying the toxic amyloids exhibited amyloid accumulation and synaptodendritic injury, leading to functional loss as evidenced by alterations in miniature excitatory post synaptic currents. The silencing of astrocytic HIF-1α not only reduced the biogenesis of ADEVs, as well as amyloid cargos, but also ameliorated neuronal synaptodegeneration. Next, we determined the effect of HIV-1 Tat-ADEVs carrying amyloids in the hippocampus of naive mice brains. Naive mice receiving the HIV-1 Tat-ADEVs, exhibited behavioural changes, and Alzheimer's 's-like pathology accompanied by synaptodegeneration. This impairment(s) was not observed in mice injected with HIF-1α silenced ADEVs. This is the first report demonstrating the role of amyloid-carrying ADEVs in mediating synaptodegeneration leading to behavioural changes associated with HAND and highlights the protective role of HIF-1α.
Assuntos
Astrócitos , Vesículas Extracelulares , HIV-1 , Hipocampo , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neurônios , Vesículas Extracelulares/metabolismo , Animais , Astrócitos/metabolismo , Camundongos , Ratos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , HIV-1/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , Humanos , Transtornos Neurocognitivos/metabolismo , Transtornos Neurocognitivos/etiologia , Infecções por HIV/metabolismo , Infecções por HIV/complicações , Masculino , Complexo AIDS Demência/metabolismoRESUMO
OBJECTIVE: To assess the prevalence and associated factors of neurocognitive disorder among people living with HIV/AIDS in South Gondar primary hospitals, North-West Ethiopia, 2023. DESIGN: Institution-based cross-sectional study design. SETTING: South Gondar primary hospitals, North-West Ethiopia. PARTICIPANTS: 608 participants were recruited using the systematic random sampling technique. MEASUREMENT: Data were collected using an interviewer-administered questionnaire and medical chart reviews. The International HIV Dementia Scale was used to screen for neurocognitive disorder. The data were entered through EPI-DATA V.4.6 and exported to SPSS V.21 statistical software for analysis. In the bivariable logistic regression analyses, variables with a value of p<0.25 were entered into a multivariable logistic regression analysis to identify factors independently associated with neurocognitive disorder. Statistical significance was declared at a value of p<0.05. RESULTS: The prevalence of neurocognitive disorder among HIV-positive participants was 39.1%. In multivariable logistic regression, lower level of education (adjusted OR (AOR)=2.94; 95% CI 1.29 to 6.82), unemployment (AOR=2.74; 95% CI 1.29 to 6.84) and comorbid medical illness (AOR=1.80; 95% CI 1.03 to 3.14) were significantly associated with neurocognitive disorder. CONCLUSION: HIV-associated neurocognitive problems affected over a third of the participants. According to the current study, comorbid medical conditions, unemployment and low educational attainment are associated with an increased risk of neurocognitive disorder. Therefore, early detection and treatment are essential.
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Infecções por HIV , Transtornos Neurocognitivos , Humanos , Etiópia/epidemiologia , Estudos Transversais , Masculino , Feminino , Adulto , Prevalência , Pessoa de Meia-Idade , Transtornos Neurocognitivos/epidemiologia , Transtornos Neurocognitivos/etiologia , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Adulto Jovem , Fatores de Risco , Complexo AIDS Demência/epidemiologia , Modelos Logísticos , Adolescente , Escolaridade , Comorbidade , Desemprego/estatística & dados numéricosRESUMO
Background: Human immunodeficiency virus (HIV) affects nearly 40 million people globally, with roughly 80% of all people living with HIV receiving antiretroviral therapy. Antiretroviral treatment suppresses viral load in peripheral tissues but does not effectively penetrate the blood-brain barrier. Thus, viral reservoirs persist in the central nervous system and continue to produce low levels of inflammatory factors and early viral proteins, including the transactivator of transcription (Tat). HIV Tat is known to contribute to chronic neuroinflammation and synaptodendritic damage, which is associated with the development of cognitive, motor, and/or mood problems, collectively known as HIV-associated neurocognitive disorders (HAND). Cannabinoid anti-inflammatory effects are well documented, but therapeutic utility of cannabis remains limited due to its psychotropic effects, including alterations within brain regions encoding reward processing and motivation, such as the nucleus accumbens. Alternatively, inhibiting monoacylglycerol lipase (MAGL) has demonstrated therapeutic potential through interactions with the endocannabinoid system. Methods: The present study utilized a reward-related operant behavioral task to quantify motivated behavior in female Tat transgenic mice treated with vehicle or MAGL inhibitor MJN110 (1 mg/kg). Brain tissue was collected to assess dendritic injury and neuroinflammatory profiles, including dendritic microtubule-associated protein (MAP2ab) intensity, microglia density, microglia morphology, astrocyte density, astrocytic interleukin-1ß (IL-1ß) colocalization, and various lipid mediators. Results: No significant behavioral differences were observed; however, MJN110 protected against Tat-induced dendritic injury by significantly upregulating MAP2ab intensity in the nucleus accumbens and in the infralimbic cortex of Tat(+) mice. No or only minor effects were noted for Iba-1+ microglia density and/or microglia morphology. Further, Tat increased GFAP+ astrocyte density in the infralimbic cortex and GFAP+ astrocytic IL-1ß colocalization in the nucleus accumbens, with MJN110 significantly reducing these measures in Tat(+) subjects. Lastly, selected HETE-related inflammatory lipid mediators in the striatum were downregulated by chronic MJN110 treatment. Conclusions: These findings demonstrate anti-inflammatory and neuroprotective properties of MJN110 without cannabimimetic behavioral effects and suggest a promising alternative to cannabis for managing neuroinflammation.
Assuntos
HIV-1 , Monoacilglicerol Lipases , Doenças Neuroinflamatórias , Animais , Feminino , Humanos , Camundongos , Complexo AIDS Demência/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/virologia , Encéfalo/patologia , Modelos Animais de Doenças , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Monoacilglicerol Lipases/antagonistas & inibidores , Monoacilglicerol Lipases/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/etiologia , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismoRESUMO
Neurocognitive disorders are mental health conditions that are caused by medical illnesses and can lead to several acquired cognitive deficits, which represent a decline from a previously attained level of functioning. The principal domains of cognitive functions include complex attention, executive function, learning and memory, language, perceptual-motor function, and social cognition. Studies have shown that people living with human immunodeficiency virus (HIV) are at a heightened risk of experiencing cognitive challenges across multiple domains. Given that, a substantial number of people live in Amhara region, assessing cognitive domains to estimate the current magnitude and factors associated with neurocognitive disorders among HIV/AIDS patients is crucial. An institutional-based cross-sectional study was conducted among 569 participants adults living with HIV attending the city's selected health facilities from March 20 to April 30, 2023. A multistage sampling technique was used. The International HIV Dementia Scale (IHDS) was used to measure the outcome of interest. The data were collected using a structured questionnaire and document review. The data were analyzed using STATA version 14. Multiple binary logistic regressions were used as the final model. A total of 501 individuals, with a response rate of 88.04% participated in the study. The overall proportion of HIV patients with neurocognitive impairment was 54.7% (95% CI 50.62-58.77). Factors associated with the neurocognitive impairment were: being widowed AOR = 3.05 (95% CI 1.47-6.31), divorced AOR = 1.95 (1.16-3.28), rural residence AOR = 2.28 (95% CI 1.02-5.09), CD4 count below 500 cells/dl AOR = 1.61 (95% CI 1.03-2.50), history of opportunistic infection AOR = 2.21 (95% CI 1.42-3.41), being in first-line drug regimen AOR = 2.92 (95% CI 1.22-7.00), being in a first-line regimen with Efavirenz AOR = 4.36 (95% CI 1.07-17.73), and impairment in daily living AOR = 2.64 (95% CI 1.39-4.99). In this study, the proportion of neurocognitive impairment was greater than that in most previous studies conducted in Ethiopia. The factors associated with the disorder were: being widowed or divorced, living in a rural area, having low CD4, having a history of opportunistic infection, receiving a first-line drug regimen, receiving efavirenz-containing drugs, and having impaired daily living. Hence, routine neuropsychological screenings should be integrated into comprehensive ART care by the regional health bureau and implemented by hospitals and health centers.
Assuntos
Infecções por HIV , Transtornos Neurocognitivos , Humanos , Masculino , Feminino , Etiópia/epidemiologia , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Transtornos Neurocognitivos/epidemiologia , Transtornos Neurocognitivos/etiologia , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/psicologia , Infecções por HIV/tratamento farmacológico , Fatores de Risco , Adulto Jovem , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/psicologia , Síndrome da Imunodeficiência Adquirida/complicações , Complexo AIDS Demência/epidemiologia , AdolescenteRESUMO
Background: Despite medical advances in Highly Active Antiretroviral Therapy (HAART), patients living with HIV continue to be at risk for developing HIV-associated neurocognitive disorders (HAND). The optimization of non-HAART interventions, including cognitive rehabilitation therapy (CRT), shows promise in reversing the impact of HAND. No data exist indicating the efficacy of CRT in remediating attention skills following neuroHIV. This paper presents a meta-analysis of randomised and non-randomised controlled trials (RCTs) to remediate attention skills following HIV CRT. Methods: The database search included literature from Google Scholar, ERIC, Cochrane Library, ISI Web of Knowledge, PubMed, PsycINFO, and grey literature published between 2013 and 2022. Inclusion criteria included studies with participants living with HIV who had undergone CRT intervention to remediate attention skills following neuroHIV. Exclusion criteria included case studies, non-human studies, and literature reviews. To assess study quality, including, randomisation, allocation concealment, participant and personnel blinding, the Cochrane Collaboration ratings system was applied. Results: A total of 14 studies met the inclusion criteria (n = 532). There were significant pre- to post-intervention between-group benefits due to CRT in the experimental group relative to control conditions for the remediation of attention skills following HIV acquisition (Hedges g = 0.251, 95% CI = 0.005 to 0.497; p < 0.05). No significant effects (p > 0.05) were demonstrated for subgroup analysis. Conclusions: To the author's knowledge, this is the first meta-analysis that exclusively analyses the remediation of attention skills in the era of HAART and neuroHIV, where all studies included participants diagnosed with HIV. The overall meta-analysis effect indicates the efficacy of CRT in remediating attention skills in HIV and HAND. It is recommended that future cognitive rehabilitation protocols to remediate attention skills should be context and population-specific and that they be supplemented by objective biomarkers indicating the efficacy of the CRT. Registration: Protocols.io (01/03/2023).
Assuntos
Atenção , Remediação Cognitiva , Infecções por HIV , Humanos , Infecções por HIV/complicações , Infecções por HIV/psicologia , Remediação Cognitiva/métodos , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/terapia , Complexo AIDS Demência/terapia , Complexo AIDS Demência/psicologiaRESUMO
La demencia asociada a virus de la inmunodeficiencia humana (VIH) es una causa de demencia rápidamente progresiva poco frecuente en la actualidad. Su aparición no se limita a las fases tardías de la enfermedad, sino que en ocasiones puede ser el síntoma de presentación. Presentamos el caso de un paciente que debutó con síntomas ansioso-depresivos y un rápido deterioro cognitivo con repercusión precoz en su funcionalidad diaria. En el estudio se detectó VIH con mayor carga viral en líquido cefalorraquídeo que en plasma. La terapia antirretroviral logró, a pesar de la tórpida evolución inicial, una mejora progresiva en la esfera cognitiva, congruente con la disminución de la carga viral. Aunque poco frecuente, el VIH sigue siendo una causa de demencia que los profesionales de atención primaria y hospitalaria no debemos olvidar. La importancia de su diagnóstico precoz radica en su carácter potencialmente reversible.(AU)
Dementia associated with human immunodeficiency virus (HIV) is currently a rare cause of rapidly progressive dementia. Its appearance is not only limited to the late phases of the disease, but can sometimes be the presenting symptom. We present the case of a patient who debuted with anxious-depressive symptoms and rapid cognitive deterioration with early repercussions on his daily functionality. HIV was detected in the study, with a higher viral load in cerebrospinal fluid than in plasma. Despite a torpid course at the beginning, antiretroviral therapy brought about a progressive improvement in the cognitive sphere, consistent with the decrease in the viral load. Although rare, HIV continues to be a cause of dementia that primary care and hospital care professionals should not forget. The relevance of its early diagnosis lies in its potentially reversible nature.(AU)
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Complexo AIDS Demência/diagnóstico , Complexo AIDS Demência/tratamento farmacológico , Complexo AIDS Demência/líquido cefalorraquidiano , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Carga Viral , Sistemas de Saúde , Espanha , HIVRESUMO
El VIH/SIDA es una enfermedad neurotrópica que afecta al sistema nervioso central y dependiendo de la fase clínica de la enfermedad genera deterioro neurológico, psiquiátrico y neuropsicológico en grado variable. Se describe el caso de un paciente que presentó un cuadro de deterioro cognitivo severo (demencia SIDA) con posterior mejoría de signos y síntomas, y establecimiento posterior de secuelas neuropsicológicas después de un año de su diagnóstico. Se comparó una evaluación neuropsicológica en etapa de deterioro cognitivo severo con otra de seguimiento, realizada un año después de iniciar el tratamiento antirretroviral. Se presentan las características clínicas del paciente utilizando el estudio de caso como herramienta metodológica y sobre la base de un procedimiento clínico y psicométrico.
HIV/AIDS is a neurotropic disease that affects the central nervous system and depending on the clinical phase of the disease generates neurological, psychiatric and neuropsychological impairment to varying degrees. The case of a patient who presented severe cognitive impairment (AIDS dementia) is described with subsequent remission of signs and symptoms, and establishment of neuropsychological sequelae after one year of diagnosis. A neuropsychological evaluation in stage of severe cognitive impairment was compared with another follow-up one year after initiating antiretroviral treatment. The clinical characteristics of the patient are presented using the case study as a methodological tool and based on a clinical and psychometric procedure.
Assuntos
Humanos , Masculino , Adulto , Encefalopatias/etiologia , Síndrome da Imunodeficiência Adquirida/complicações , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , Complexo AIDS Demência , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Disfunção Cognitiva/etiologia , Testes NeuropsicológicosRESUMO
ABSTRACT Major neurocognitive disorder due to multiple etiologies, or dementia due to multiple etiologies (DME), is a term coined by the Diagnostic and Statistical Manual of Mental Disorders to refer to complex cases when multiple pathologies, such as Alzheimer's disease, Lewy Bodies, human immunodeficiency virus (HIV), vascular-related brain damage or frontotemporal lobar degeneration, are identified as contributing to neurocognitive impairment and/or behavioral alterations, based on patient's neuroimaging tests, laboratorial exams, associated symptomatology and medical history. In this study, we report the case of a 63-year-old male patient who presented with parkinsonism symptoms, aphasia and cognitive impairment on multiple domains after cerebral toxoplasmosis related to acquired immunodeficiency syndrome, vascular damage and a history of alcohol abuse. We discuss the neurocognitive and neurobehavioral variables that characterized this diagnosis, as well as the importance of the differential diagnosis of DME on the field of neuropsychology of aging and, especially, for individuals living with HIV infection.
RESUMO Transtorno neurocognitivo maior devido a múltiplas etiologias, ou demência por múltiplas etiologias (DME), é um termo estabelecido pelo Manual Diagnóstico e Estatístico de Transtornos Mentais para se referir a casos complexos em que múltiplas patologias, como a Doença de Alzheimer, Corpos de Lewy, o vírus da imunodeficiência humana (HIV), danos de origem vascular ou a degeneração lobar frontotemporal, são identificados como contribuintes para o comprometimento neurocognitivo e/ou para alterações comportamentais, com base em testes de neuroimagem do paciente, exames laboratoriais, sintomatologia associada e histórico médico. Neste artigo, relatamos o caso de um paciente do sexo masculino de 63 anos que apresentou sintomas de parkinsonismo, afasia e comprometimento cognitivo em múltiplos domínios após neurotoxoplasmose relacionada à síndrome da imunodeficiência adquirida, dano vascular e histórico de abuso de álcool. Foram discutidas as variáveis neurocognitivas e neurocomportamentais que caracterizaram esse diagnóstico, assim como a importância do diagnóstico diferencial de DME para a neuropsicologia do envelhecimento e, especialmente, para indivíduos portadores do HIV.
Assuntos
Humanos , Comportamento , Complexo AIDS Demência , Toxoplasmose Cerebral , Cognição , Transtornos Neurocognitivos , NeuropsicologiaRESUMO
Abstract INTRODUCTION: The number of human immunodeficiency virus-associated neurocognitive disorders has increased, reaching more than 50% of the cases. However, there are currently no substantial data on the screening methods for this disease. This study aimed to evaluate and compare the Mini-Mental State Examination to the Montreal Cognitive Assessment in human immunodeficiency virus-infected patients. METHODS: This was an observational study comprising 82 human immunodeficiency virus-positive individuals with and without cognitive complaints. RESULTS: Positive correlation (p<0.001) between the Mini-Mental State Examination and the Montreal Cognitive Assessment test scores was observed, but the mean scores revealed that the Mini-Mental State Examination showed worse performance for trails (p<0.001), cube copying (p<0.001), and clock drawing (p<0.001) than the Montreal Cognitive Assessment. CONCLUSIONS: The Mini-Mental State Examination and the Montreal Cognitive Assessment tests should be used concomitantly for the assessment of human immunodeficiency virus-associated neurocognitive disorders, but visuoexecutive and visuospatial dysfunctions are better evaluated using the Montreal Cognitive Assessment test than the Mini-Mental State Examination.