RESUMO
Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.
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Envelhecimento , Demência , Países em Desenvolvimento , Humanos , Demência/diagnóstico , Demência/terapia , Demência/epidemiologia , Encéfalo , Congressos como Assunto , Pesquisa BiomédicaRESUMO
BACKGROUND: Cognitive impairment is reported as a common complication in adult tuberculous meningitis (TBM), yet few studies have systematically assessed the frequency and nature of impairment. Moreover, the impact of impairment on functioning and medication adherence has not been described. METHODS: A cognitive test battery (10 measures assessing 7 cognitive domains) was administered to 34 participants with human immunodeficiency virus (HIV)-associated TBM 6 months after diagnosis. Cognitive performance was compared with that a comparator group of 66 people with HIV without a history of tuberculosis. A secondary comparison was made between participants with TBM and 26 participants with HIV 6 months after diagnosis of tuberculosis outside the central nervous system (CNS). Impact on functioning was evaluated, including through assessment of medication adherence. RESULTS: Of 34 participants with TBM, 16 (47%) had low performance on cognitive testing. Cognition was impaired across all domains. Global cognitive performance was significantly lower in participants with TBM than in people with HIV (mean T score, 41 vs 48, respectively; P < .001). These participants also had lower global cognition scores than those with non-CNS tuberculosis (mean global T score, 41 vs 46; P = .02). Functional outcomes were not significantly correlated with cognitive performance in the subgroup of participants in whom this was assessed (n = 19). CONCLUSIONS: Low cognitive performance following HIV-associated TBM is common. This effect is independent of, and additional to, effects of HIV and non-CNS tuberculosis disease. Further studies are needed to understand longer-term outcomes, clarify the association with treatment adherence, a key predictor of outcome in TBM, and develop context-specific tools to identify individuals with cognitive difficulties in order to improve outcomes in TBM.
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Disfunção Cognitiva , Infecções por HIV , Tuberculose Meníngea , Adulto , Humanos , Tuberculose Meníngea/complicações , Tuberculose Meníngea/diagnóstico , Tuberculose Meníngea/tratamento farmacológico , Infecções por HIV/complicações , Disfunção Cognitiva/complicaçõesRESUMO
Depression and cognitive impairment, which commonly coexist in people with HIV (PWH), have been identified as potential barriers to optimal antiretroviral therapy (ART) adherence. We investigated associations between cognitive performance, depression (as well as other sociodemographic, psychosocial and psychiatric variables) and ART adherence in a South African cohort of PWH with comorbid major depressive disorder (MDD). Cognitive performance and ART adherence were assessed at two time points 8 months apart (Nbaseline = 105, Nfollow-up = 81). Adherence was indicated by self-report, objective measures (Wisepill usage and plasma tenofovir-diphosphate levels), and HIV viral suppression. Mixed-effects regression models examined associations across both time points. Univariate models detected no significant associations between cognitive performance (globally and within-domain) and ART adherence. Multivariate modelling showed increased depression severity (ß = - 0.54, p < 0.001) and problematic alcohol use (ß = 0.73, p = 0.015) were associated with worse adherence as measured subjectively. Being female (OR 0.27, p = 0.048) and having better global cognitive performance (OR 1.83, p = 0.043) were associated with better adherence as indicated by viral suppression. This study identifies poor global cognitive performance, as well as depression and problematic alcohol use, as potential barriers to optimal ART adherence in PWH and comorbid MDD. Hence, clinicians could consider assessing for cognitive deficits, depression, and problematic alcohol use, and should endeavour to provide the appropriate support so as to improve adherence.
Assuntos
Transtorno Depressivo Maior , Infecções por HIV , Humanos , Feminino , Masculino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/epidemiologia , Depressão/complicações , Depressão/epidemiologia , Depressão/psicologia , África do Sul/epidemiologia , Adesão à Medicação/psicologia , Antirretrovirais/uso terapêutico , CogniçãoRESUMO
Mental health and neurocognitive functioning remain a concern among people living with HIV. Symptomatic neurocognitive impairment (NCI) and mental illness can cause difficulties in daily functioning, including problems adhering to treatment. However, many healthcare workers in resource-limited settings have limited knowledge about the relationship between HIV and NCI. A synthesis of available literature on mental health and NCI training provided to healthcare workers delivering HIV services in Africa, is lacking. We conducted a scoping review of published literature to identify training interventions which targeted healthcare workers providing careto people with HIV in Africa. Ten studies met the inclusion criteria. One study focused on NCI, two studies mentioned HIV-associated dementia and seven studies were centred on common mental health disorders. Most studies used a multi-method training approach, with pre-and post-testing as the main evaluation technique. This review highlights the gap in training interventions addressing NCI in Africa. Although there is some commitment to building capacity for mental health and NCI assessment among healthcare workers in this setting, this review suggests that there is a need for research to develop and evaluate training interventions for healthcare workers delivering HIV services in Africa.
Assuntos
Infecções por HIV , Humanos , Infecções por HIV/terapia , África , Atenção à Saúde , Pessoal de Saúde/psicologia , CogniçãoRESUMO
BACKGROUND: The late-onset efavirenz neurotoxicity syndrome (LENS) presents as ataxia and/or encephalopathy with supratherapeutic efavirenz plasma concentrations (>4 µg/mL). Efavirenz is primarily metabolized by cytochrome P450 2B6 (CYP2B6), with CYP2A6 as an accessory pathway. We hypothesized that participants with LENS would predominantly be CYP2B6 slow metabolizers. The aim of our study was to determine the frequency of CYP2B6 slow metabolizers in participants with LENS. METHODS: Adult HIV-positive participants on efavirenz-based antiretroviral therapy presenting with LENS were prospectively enrolled. Genetic polymorphisms known to be associated with increased efavirenz plasma concentrations in CYP2B6 (rs3745274, rs28399499, rs4803419) and CYP2A6 (rs28399433) were selected and used to determine proportions of slow metabolizers. Pharmacokinetic analyses were performed using liquid chromatography-tandem mass spectrometry. Median (IQR) plasma efavirenz and 8-hydroxyefavirenz were described. RESULTS: Fifteen participants were enrolled. Thirteen (13/15) were Black-African and 13 were female. Median weight was 49.9kg with a median duration on efavirenz of 2.2 years. All 15 participants were successfully genotyped as slow CYP2B6 metabolizers, with 6 participants additionally having CYP2A6 heterozygous genotype. Thirteen were receiving the CYP2A6 enzyme inhibitor isoniazid, and all 15 were genotypic NAT2 slow or intermediate acetylators. Efavirenz plasma concentration was markedly increased at 50.5 (47.0-65.4) µg/mL; 8-hydroxyefavirenz concentration was markedly decreased at 0.10 (0.07-0.15) µg/mL. CONCLUSIONS: Our cohort provides definitive evidence that LENS is associated with the CYP2B6 slow metabolizer genotype, with a median efavirenz plasma concentrationâ >12-fold higher than the defined upper limit of the therapeutic range. Isoniazid and low body weight are important contributors to LENS development.
Assuntos
Fármacos Anti-HIV , Arilamina N-Acetiltransferase , Infecções por HIV , Síndromes Neurotóxicas , Adulto , Alcinos/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Arilamina N-Acetiltransferase/genética , Benzoxazinas/efeitos adversos , Ciclopropanos/uso terapêutico , Citocromo P-450 CYP2B6/genética , Feminino , Humanos , Isoniazida/uso terapêutico , Masculino , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/genética , Farmacogenética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Cognitive performance in people with HIV (PWH) may be affected by brain injury attributable to the infection itself, by other medical and psychiatric comorbidities (including major depressive disorder; MDD), and by psychosocial factors (e.g., education, food insecurity). We investigated effects of these variables on cognitive performance in a South African cohort of PWH with comorbid MDD and incomplete adherence to antiretroviral therapy (ART). We also examined (a) associations of depression severity with cognitive performance, and (b) whether improvement in depression led to improved cognitive performance. Participants (N = 105) completed baseline neuropsychological, psychiatric, and sociodemographic assessments. Subsequently, 33 were assigned to a cognitive-behavioural therapy for ART adherence and depression (CBT-AD) and 72 to standard-of-care treatment. Eight months post-baseline, 81 (nCBT-AD = 29) repeated the assessments. We investigated (a) baseline associations between sociodemographic, medical, and psychiatric variables and cognitive performance, (b) whether, from baseline to follow-up, depression and cognitive performance improved significantly more in CBT-AD participants, and (c) associations between post-intervention improvements in depression and cognitive performance. At baseline, less education (ß = 0.62) and greater food insecurity (ß = -0.20) predicted poorer overall cognitive performance; more severe depression predicted impairment in the attention/working memory domain only (ß = -0.25). From baseline to follow-up, depression decreased significantly more in CBT-AD participants (p = .017). Improvement over time in depression and cognitive performance was not significantly associated except in the attention/working memory domain (p = .026). Overall, factors associated with cognitive performance were unrelated to brain injury. We conclude that clinicians examining PWH presenting with cognitive difficulties must assess depression, and that researchers investigating cognitive impairment in PWH must collect information on psychosocial factors.
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Transtorno Depressivo Maior , Infecções por HIV , Humanos , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Depressão/complicações , Depressão/epidemiologia , Depressão/psicologia , África do Sul/epidemiologia , Resultado do Tratamento , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , CogniçãoRESUMO
The prevalence of HIV-associated neurocognitive impairment (H-NCI) is concerning. Individuals on effective antiretroviral therapy (ART) may still be at risk for H-NCI as they experience longer life expectancies. There are, however, few professionals with knowledge and skills to identify H-NCI, in low- and middle-income countries. We explored qualitatively, primary healthcare workers' knowledge and views of H-NCI, in the era of effective ART, particularly their views toward task-sharing of H-NCI screening from specialists to mid-level or lay healthcare providers. The first phase of data collection involved two focus group discussions (FGDs) 23 primary healthcare workers from two facilities in the Western Cape participated in the FGDs. In the second phase of data collection12 individual, in-depth interviews were conducted in KwaZulu-Natal. Using thematic analysis, several key themes emerged. Although healthcare providers were unable to specifically identify H-NCI, they described several HIV disease and treatment related or mental health comorbidities that could be responsible for the symptoms. Despite healthcare workers reporting low frequencies of H-NCI, they favoured receiving training to screen for H-NCI with a view toward providing holistic care.
Assuntos
Infecções por HIV , Grupos Focais , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Pessoal de Saúde/psicologia , Humanos , Atenção Primária à Saúde , Pesquisa Qualitativa , África do Sul/epidemiologiaRESUMO
Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) criteria are frequently used to describe cognitive impairment in persons living with HIV (PLWH) across diverse populations globally. These criteria typically find 20-60% of PLWH meet criteria for HAND, which does not tally with clinical observations in the modern era that cognitive disorders present relatively infrequently. Most with HAND have asymptomatic neurocognitive impairment; however, the significance of low cognitive test performance without symptoms is uncertain. Methods underlying HAND criteria carry a false-positive rate that can exceed 20%. Comorbidities, education, and complex socioeconomic factors can influence cognitive test performance, further increasing the potential for misclassification. We propose a new framework to characterize cognitive impairment in PLWH that requires a clinical history and acknowledges the multifactorial nature of low cognitive test performance. This framework is intended to be applicable across diverse populations globally, be more aligned with clinical observations, and more closely represent HIV brain pathology.
Assuntos
Disfunção Cognitiva , Infecções por HIV , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , HIV , Infecções por HIV/complicações , Humanos , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/epidemiologia , Transtornos Neurocognitivos/etiologia , Testes NeuropsicológicosRESUMO
There is wide variation in the reported prevalence of cognitive impairment in people with HIV (PWH). Part of this variation may be attributable to different studies using different methods of combining neuropsychological test scores to classify participants as either cognitively impaired or unimpaired. Our aim was to determine, in a South African cohort of PWH (N = 148), (a) how much variation in reported rates was due to method used to define cognitive impairment and (b) which method correlated best with MRI biomarkers of HIV-related brain pathology. Participants completed detailed neuropsychological assessment and underwent 3 T structural MRI and diffusion tensor imaging (DTI). We used the neuropsychological data to investigate 20 different methods of determining HIV-associated cognitive impairment. We used the neuroimaging data to obtain volumes for cortical and subcortical grey matter and total white matter and DTI metrics for several white matter tracts. Applying each of the 20 methods to the cognitive dataset resulted in a wide variation (20-97%) in estimated rates of impairment. Logistic regression models showed no method was associated with HIV-related neuroimaging abnormalities as measured by structural volumes or DTI metrics. We conclude that for the population from which this sample was drawn, much of the variation in reported rates of cognitive impairment in PWH is due to the method of classification used, and that none of these methods accurately reflects biological effects of HIV in the brain. We suggest that defining HIV-associated cognitive impairment using neuropsychological test performance only is insufficient; pre-morbid functioning, co-morbidities, cognitive symptoms, and functional impairment should always be considered.
Assuntos
Complexo AIDS Demência/classificação , Complexo AIDS Demência/diagnóstico , Adulto , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Neuroimagem , África do SulRESUMO
Neurocognitive impairment (NCI) associated with the human immunodeficiency virus (HIV) remains prevalent amongst people living with HIV. Testing for HIV-associated NCI in routine clinical care is limited in South Africa and reasons for this are unclear. We conducted an online survey amongst healthcare workers (HCW) to assess HIV-associated NCI knowledge and current practices. The final sample included four hundred surveys (n=400). Chi-square analyses were used to explore HCW knowledge of HIV-associated NCI and screening tools. One-way ANOVA was used to compare mean responses between HCW categories. We observed low awareness of HIV-associated NCI terminology and screening tools. HCW seldom suspected NCI among patients and screening practices were uncommon. Referrals for further NCI investigations were never requested. HCW expressed a desire to receive further training to identify HIV associated NCI. The current study highlights the context of HIV-associated NCI knowledge and practices among front-line HIV HCW in resource-limited settings.
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Infecções por HIV , Infecções por HIV/epidemiologia , Pessoal de Saúde , Humanos , Programas de Rastreamento , África do Sul/epidemiologia , Inquéritos e QuestionáriosRESUMO
Efavirenz (EFZ) has been associated with neuropsychiatric side effects. Recently, the 8-hydroxy-EFZ (8OH-EFZ) metabolite has been shown to be a potent neurotoxin in vitro, inducing neuronal damage at concentrations of 3.3 ng/ml. EFZ induced similar neuronal damage at concentrations of 31.6 ng/ml. We investigated the effect of genotype and blood-brain barrier integrity on EFZ metabolite concentrations in cerebrospinal fluid (CSF). We measured CSF drug concentrations in subjects from two separate study populations: 47 subjects with tuberculous meningitis (TBM) coinfection in Vietnam receiving 800 mg EFZ with standard antituberculous treatment and 25 subjects from the PARTITION study in the United Kingdom without central nervous system infection receiving 600 mg EFZ. EFZ and metabolite concentrations in CSF and plasma were measured and compared with estimates of effectiveness and neurotoxicity from available published in vitro and in vivo data. The effect of the CYP2B6 c.516GâT genotype (GG genotype, fast EFV metabolizer status; GT genotype, intermediate EFV metabolizer status; TT genotype, slow EFV metabolizer status) was examined. The mean CSF concentrations of EFZ and 8OH-EFZ in the TBM group were 60.3 and 39.3 ng/ml, respectively, and those in the no-TBM group were 15.0 and 5.9 ng/ml, respectively. Plasma EFZ and 8OH-EFZ concentrations were similar between the two groups. CSF EFZ concentrations were above the in vitro toxic concentration in 76% of samples (GG genotype, 61%; GT genotype, 90%; TT genotype, 100%) in the TBM group and 13% of samples (GG genotype, 0%; GT genotype, 18%; TT genotype, 50%) in the no-TBM group. CSF 8OH-EFZ concentrations were above the in vitro toxic concentration in 98% of the TBM group and 87% of the no-TBM group; levels were independent of genotype but correlated with the CSF/plasma albumin ratio. Potentially neurotoxic concentrations of 8OH-EFZ are frequently observed in CSF independently of the CYP2B6 genotype, particularly in those with impaired blood-brain barrier integrity.
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Benzoxazinas/farmacologia , Benzoxazinas/uso terapêutico , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , Tuberculose Meníngea/tratamento farmacológico , Alcinos , Barreira Hematoencefálica , Ciclopropanos , GenótipoRESUMO
The central nervous system has been proposed as a sanctuary site where HIV can escape antiretroviral control and develop drug resistance. HIV-1 RNA can be at higher levels in CSF than plasma, termed CSF/plasma discordance. We aimed to examine whether discordance in CSF is associated with low level viraemia (LLV) in blood. In this MRC-funded multicentre study, we prospectively recruited patients with LLV, defined as one or more episode of unexplained plasma HIV-1 RNA within 12 months, and undertook CSF examination. Separately, we prospectively collected CSF from patients undergoing lumbar puncture for a clinical indication. Patients with durable suppression of viraemia and no evidence of CNS infection were identified as controls from this group. Factors associated with CSF/plasma HIV-1 discordance overall were examined. One hundred fifty-three patients were recruited across 13 sites; 40 with LLV and 113 undergoing clinical lumbar puncture. Seven of the 40 (18 %) patients with LLV had CSF/plasma discordance, which was significantly more than 0/43 (0 %) with durable suppression in blood from the clinical group (p = 0.005). Resistance associated mutations were shown in six CSF samples from discordant patients with LLV (one had insufficient sample for testing), which affected antiretroviral therapy at sampling in five. Overall discordance was present in 20/153 (13 %) and was associated with nadir CD4 but not antiretroviral concentrations in plasma or CSF. CSF/plasma discordance is observed in patients with LLV and is associated with antiretroviral resistance associated mutations in CSF. The implications for clinical practice require further investigation.
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Infecções por HIV/diagnóstico , RNA Viral/sangue , RNA Viral/líquido cefalorraquidiano , Viremia/diagnóstico , Adulto , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Sistema Nervoso Central/virologia , Farmacorresistência Viral/genética , Feminino , Infecções por HIV/sangue , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , HIV-1/genética , HIV-1/crescimento & desenvolvimento , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , RNA Viral/antagonistas & inibidores , Viremia/sangue , Viremia/líquido cefalorraquidiano , Viremia/tratamento farmacológicoRESUMO
INTRODUCTION: HIV-1 RNA can be found at higher levels in cerebrospinal fluid (CSF) than in plasma, termed CSF/plasma discordance. The clinical significance of CSF/plasma discordance is not known and the degree of discordance considered important varies. We aimed to determine whether a panel of CSF cytokines, chemokines and associated mediators were raised in patients with CSF/plasma discordance at different levels. METHODS: A nested case-control study of 40 CSF samples from the PARTITION study. We used a cytometric bead array to measure CSF mediator concentrations in 19 discordant and 21 non-discordant samples matched for plasma HIV-1 RNA. Discordant samples were subdivided into 'high discordance' (>1log10) and 'low discordance' (0.5-1log10, or ultrasensitive discordance). CSF mediators significant in univariate analysis went forward to two-way unsupervised hierarchical clustering based on the patterns of relative mediator concentrations. RESULTS: In univariate analysis 19 of 21 CSF mediators were significantly higher in discordant than non-discordant samples. There were no significant differences between samples with high versus low discordance. The samples grouped into two clusters which corresponded to CSF/plasma discordance (p<0.0001). In cluster one all mediators had relatively high abundance; this included 18 discordant samples and three non-discordant samples. In cluster two all mediators had relatively low abundance; this included 18 non-discordant samples and one non-discordant sample with ultrasensitive discordance only. CONCLUSIONS: CSF/plasma discordance is associated with potentially damaging neuroinflammatory process. Patients with discordance at lower levels (ie. 0.5-1log10) should also be investigated as mediator profiles were similar to those with discordance >1log10. Sensitive testing may have a role to determine whether ultrasensitive discordance is present in those with low level CSF escape.
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Infecções por HIV , HIV-1 , Mediadores da Inflamação , RNA Viral , Adulto , Feminino , Infecções por HIV/sangue , Infecções por HIV/líquido cefalorraquidiano , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/biossíntese , RNA Viral/líquido cefalorraquidianoRESUMO
INTRODUCTION: To examine electroencephalogram (EEG) as a diagnostic tool for late-onset efavirenz (EFV) neurotoxicity syndrome (LENS), an uncommon but severe and potentially fatal complication of EFV therapy. METHODS: We conducted a Retrospective case-control study. EEGs from confirmed cases of LENS (clinical syndrome and plasma EFV >4ug/mL) recorded from June 2016 to May 2021 were compared with control EEGs from the same time-period. Controls were adults (18-70 years) with a similar indication for EEG (eg. encephalopathy or confusion), dysrhythmia generalised grade II, and LENS excluded. EEGs were reviewed by two blinded interpreters given a description of the characteristic EEG changes, ie. persistent, diffuse, high voltage, bisynchronous, monomorphic 4-7 Hz theta frequency waveforms with transient attenuation on eye opening. Interpreters were asked to determine whether EEGs showed definite, probable or no changes. RESULTS: Thirteen LENS cases were compared with 50 control EEGs. Interpreter 1 labelled 11/13 LENS cases as having define or probable changes, and interpreter 2 labelled 10/13. Interpreter 1 labelled probable changes in 1/50 controls and interpreter 2 in 3/50. Neither interpreter labelled any controls as having definite changes. Interrater reliability was good with 95% agreement and a Cohen's kappa of 0.83. Sensitivity of EEG under these conditions for the diagnosis of LENS was 85% and 77% for interpreters 1 and 2 respectively, and specificity was 98% and 94%. CONCLUSIONS: EEG is a useful tool in the diagnosis of LENS which can be used to aid clinical decisions while awaiting EFV levels, or in low-resource settings where EFV levels are not available.
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Eletroencefalografia , Síndromes Neurotóxicas , Adulto , Humanos , Estudos Retrospectivos , Estudos de Casos e Controles , Reprodutibilidade dos Testes , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/etiologiaRESUMO
Women with HIV (WWH) may be more vulnerable to cognitive impairment than men with HIV (MWH), which may be explained by the direct effects of HIV or by sociodemographic and psychiatric characteristics. We recruited 105 people with HIV (PWH; 76 women) with incomplete antiretroviral therapy adherence, comorbid major depressive disorder, and socioeconomically disadvantaged backgrounds. Participants completed neuropsychological testing and measures gathering sociodemographic, medical, and psychiatric information. We compared WWH and MWH cognitive performance using unadjusted and adjusted regressions, and within each respective group, we explored predictors of cognitive performance. Results showed no significant between-sex differences in cognitive performance, both globally and within domains. Fewer years of education (ß = 0.94), illiteracy (ß = 4.55), and greater food insecurity (ß = -0.28) predicted lower cognitive performance in WWH but not MWH. We conclude that sex differences in PWH are likely due to sample characteristics representing broader inequalities, rather than true biological differences.
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Transtorno Depressivo Maior , Infecções por HIV , Humanos , Masculino , Feminino , Transtorno Depressivo Maior/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Caracteres Sexuais , África do Sul/epidemiologia , CogniçãoRESUMO
Current approaches to classifying cognitive impairment in people living with HIV can overestimate disease burden and lead to ambiguity around disease mechanisms. The 2007 criteria for HIV-associated neurocognitive disorders (HAND), sometimes called the Frascati criteria, can falsely classify over 20% of cognitively healthy individuals as having cognitive impairment. Minimum criteria for HAND are met on the basis of performance on cognitive tests alone, which might not be appropriate for populations with diverse educational and socioeconomic backgrounds. Imprecise phenotyping of cognitive impairment can limit mechanistic research, biomarker discovery and treatment trials. Importantly, overestimation of cognitive impairment carries the risk of creating fear among people living with HIV and worsening stigma and discrimination towards these individuals. To address this issue, we established the International HIV-Cognition Working Group, which is globally representative and involves the community of people living with HIV. We reached consensus on six recommendations towards a new approach for diagnosis and classification of cognitive impairment in people living with HIV, intended to focus discussion and debate going forward. We propose the conceptual separation of HIV-associated brain injury - including active or pretreatment legacy damage - from other causes of brain injury occurring in people living with HIV. We suggest moving away from a quantitative neuropsychological approach towards an emphasis on clinical context. Our recommendations are intended to better represent the changing profile of cognitive impairment in people living with HIV in diverse global settings and to provide a clearer framework of classification for clinical management and research studies.
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Disfunção Cognitiva , Infecções por HIV , Humanos , HIV , Consenso , Infecções por HIV/complicações , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Transtornos Neurocognitivos , Testes NeuropsicológicosRESUMO
HIV-associated neurocognitive impairment (H-NCI) remains a common comorbidity, which may affect several key health outcomes among people with HIV. However, there are shortages of appropriately skilled healthcare workers able to identify and manage H-NCI in low- and middle-income countries. We conducted an exploratory, quasi-experimental, pre- and post-cohort training intervention in KwaZulu-Natal, South Africa. Thirty-four healthcare workers (two general medical doctors, twenty-two nurses, and ten adherence counsellors) from six facilities and a mobile clinic unit attended two, two-hour face-to-face, training sessions. The training included knowledge and skill transfer components. Pre- and post-knowledge questionaries demonstrated an improvement among 82% (n = 28) of the attendees from all three cadres. Knowledge was retained by 88% (n = 30) of the attendees after eight weeks. The H-NCI screening tools were administered with 78% accuracy. After eight weeks, two general medical doctors and eight senior nurses were able to accurately administer the tool. The Primary Healthcare H-NCI training was successful in improving knowledge among primary healthcare workers; however, several healthcare workers experienced challenges with administering such tools.
RESUMO
OBJECTIVE: Although many studies report that women with HIV (WWH) are more vulnerable to cognitive impairment than men with HIV (MWH), this trend is not described consistently in the literature. In this systematic review and meta-analysis, we investigated whether the weight of evidence supports the existence of a significant sex difference in cognitive functioning among people with HIV and, if so, whether specific domains are affected. METHOD: A systematic literature search retrieved 4,062 unique articles published between January 2000 and June 2019. Eligibility criteria were that studies directly compared adult WWH and MWH using a neuropsychological test battery. After extensive screening, we included 11 studies in the systematic review (N = 3,333) and 6 in the meta-analysis (N = 2,852). RESULTS: Six studies included in the systematic review found WWH performed significantly more poorly on measures of cognitive performance than MWH; the other five found no sex differences. Meta-analytic results indicated that WWH performed significantly more poorly than MWH in three cognitive domains (psychomotor coordination, visuospatial learning, and memory), but magnitudes of effect sizes were small (d = -.16, -.43, and - .30, respectively). Analyses detected no sex differences in global cognitive functioning and in the other cognitive domains. CONCLUSIONS: Sex differences in cognitive performance are small, and sociodemographic and psychiatric characteristics of WWH and MWH differ between studies. Cognitive differences between WWH and MWH may be explained by sex-based variation in these characteristics, the impact of which seems to outweigh that of HIV-related clinical variables (e.g., CD4 count and viral load).
Assuntos
Disfunção Cognitiva , Infecções por HIV , Adulto , Cognição , Feminino , Infecções por HIV/complicações , Humanos , Aprendizagem , Masculino , Testes NeuropsicológicosRESUMO
BACKGROUND: Acute encephalitis syndrome (AES) is commonly seen among hospitalized Nepali children. Japanese Encephalitis (JE) accounts for approximately one-quarter of cases. Although poor prognostic features for JE have been identified, and guide management, relatively little is reported on the remaining three-quarters of AES cases. METHODS: Children with AES (n = 225) were identified through admission records from two hospitals in Kathmandu between 2006 and 2008. Patients without available lumbar puncture results (n = 40) or with bacterial or plasmodium infection (n = 40) were analysed separately. The remaining AES patients with suspected viral aetiology were classified, based on positive IgM antibody in serum or cerebral spinal fluid, as JE (n = 42) or AES of unknown viral aetiology (n = 103); this latter group was sub-classified into Non-JE (n = 44) or JE status unknown (n = 59). Bad outcome was defined as death or neurological sequelae at discharge. RESULTS: AES patients of suspected viral aetiology more frequently had a bad outcome than those with bacterial or plasmodium infection (31% versus 13%; P = 0.039). JE patients more frequently had a bad outcome than those with AES of unknown viral aetiology (48% versus 24%; P = 0.01). Bad outcome was independently associated in both JE and suspected viral aetiology groups with a longer duration of fever pre-admission (P = 0.007; P = 0.002 respectively) and greater impairment of consciousness (P = 0.02; P < 0.001). A higher proportion of JE patients presented with a focal neurological deficit compared to patients of unknown viral aetiology (13/40 versus 11/103; P = 0.005). JE patients weighed less (P = 0.03) and exhibited a higher respiratory rate (P = 0.003) compared to Non-JE patients. CONCLUSIONS: Nepali children with AES of suspected viral aetiology or with JE frequently suffered a bad outcome. Despite no specific treatment, patients who experienced a shorter duration of fever before hospital admission more frequently recovered completely. Prompt referral may allow AES patients to receive potentially life-saving supportive management. Previous studies have indicated supportive management, such as fluid provision, is associated with better outcome in JE. The lower weight and higher respiratory rate among JE patients may reflect multiple clinical complications, including dehydration. The findings suggest a more systematic investigation of the influence of supportive management on outcome in AES is warranted.
Assuntos
Encefalite/complicações , Encefalite/patologia , Doenças do Sistema Nervoso/epidemiologia , Adolescente , Anticorpos Antivirais/sangue , Anticorpos Antivirais/líquido cefalorraquidiano , Bactérias/isolamento & purificação , Criança , Pré-Escolar , Encefalite/etiologia , Encefalite/mortalidade , Feminino , Hospitais , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/líquido cefalorraquidiano , Lactente , Masculino , Nepal , Doenças do Sistema Nervoso/etiologia , Plasmodium/isolamento & purificação , Prognóstico , Estudos Retrospectivos , Punção Espinal , Análise de Sobrevida , Resultado do TratamentoRESUMO
HIV-associated CD8-encephalitis (HIV-CD8E) is a severe inflammatory disorder dominated by infiltration of the brain by CD8+ T-lymphocytes. It occurs in people with HIV, typically when the virus is apparently well-controlled by antiretroviral treatment (ART). HIV-CD8E presents with symptoms and signs related to marked cerebral inflammation and swelling, and can lead to coma and death unless treated promptly with corticosteroids. Risk events such as intercurrent infection, antiretroviral therapy interruption, immune reconstitution inflammatory syndrome (IRIS) after starting ART, and concomitant associations such as cerebrospinal fluid (CSF) HIV viral escape have been identified, but the pathogenesis of the disorder is not known. We present the largest case series of HIV-CD8E to date (n = 23), representing histopathologically confirmed cases in the UK. We also summarize the global literature representing all previously published cases with histopathological confirmation (n = 30). A new variant of HIV-CD8E is described, occurring on a background of HIV encephalitis (HIVE).Together these series, totalling 53 patients, provide new insights. CSF HIV viral escape was a frequent finding in HIV-CD8E occurring in 68% of those with CSF available and tested; ART interruption and IRIS were important, both occurring in 27%. Black ethnicity appeared to be a key risk factor; all but two UK cases were African, as were the majority of the previously published cases in which ethnicity was stated. We discuss potential pathogenic mechanisms, but there is no unifying explanation over all the HIV-CD8E scenarios.