Investigation of Molecular Properties of Antiretroviral Agents to Enhance CNS Penetration Abilities for the Treatment of Cognitive Impairment in HIV-Associated Neurocognitive Disorder

2020 ◽  
Vol 11 (14) ◽  
pp. 2034-2038
Author(s):  
Chhanda Charan Danta ◽  
Poonam Piplani
Keyword(s):  
Cognitive Impairment ◽  
Molecular Properties ◽  
Neurocognitive Disorder ◽  
Antiretroviral Agents ◽  
Hiv Associated Neurocognitive Disorder ◽  
Cns Penetration

scholarly journals Prefrontal gating of sensory input differentiates cognitively impaired and unimpaired aging adults with HIV

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Rachel K Spooner ◽  
Alex I Wiesman ◽  
Jennifer O’Neill ◽  
Mikki D Schantell ◽  
Howard S Fox ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Neural Activity ◽  
Cognitively Impaired ◽  
Neurocognitive Disorder ◽  
Spontaneous Neural Activity ◽  
Somatosensory Input ◽  
Hiv Associated Neurocognitive Disorder ◽  
Aging Adults ◽  
The Impact ◽  
Prefrontal Cortices

Abstract Despite effective therapies that have extended the life expectancy of persons living with HIV, 35–70% of these adults still develop some form of cognitive impairment, and with a growing population of aging adults with HIV, the prevalence of these cognitive deficits is likely to increase. The mechanisms underlying these HIV-associated neurocognitive disorders remain poorly understood but are often accelerated by the aging process and accompanied by disturbances in sensory processing, which may contribute to the observed cognitive decline. The goal of the current study was to identify the impact of aging on HIV-related alterations in inhibitory processing and determine whether such alterations are related to cognitive impairment in neuroHIV. We used magnetoencephalographic imaging, advanced time series analysis methods, and a paired-pulse stimulation paradigm to interrogate inhibitory processing in 87 HIV-infected aging adults and 92 demographically matched uninfected controls (22–72 years old). Whole-brain maps linking age and neural indices were computed for each group and compared via Fisher’s Z transformations. Peak voxel time-series data were also extracted from the resulting images to quantify the dynamics of spontaneous neural activity preceding stimulation onset in each group. Whole-brain analyses using the somatosensory gating index, a metric of inhibitory processing and age distinguished impaired adults with HIV from unimpaired HIV-infected adults and controls. Briefly, younger cognitively impaired adults with HIV strongly utilized the prefrontal cortices to gate somatosensory input, and the role of this region in gating was uniquely and significantly modulated by aging only in impaired adults with HIV. Spontaneous neural activity preceding stimulus onset was also significantly elevated in the prefrontal cortices of those with HIV-associated neurocognitive disorder, and this elevation was significantly related to the CD4 nadir across both HIV-infected groups. This is the first study to examine the impact of aging on inhibitory processing in HIV-infected adults with and without cognitive impairment. Our findings suggest that young adults with HIV-associated neurocognitive disorder utilize the prefrontal cortices to gate (i.e. suppress) redundant somatosensory input, and that this capacity uniquely diminishes with advancing age in impaired adults with HIV.

scholarly journals Tanshinone IIA Alleviates CCL2-Induced Leaning memory and Cognition Impairment in Rats: A Potential Therapeutic Approach for HIV-Associated Neurocognitive Disorder

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Yuan-jun Liao ◽  
Jian-min Chen ◽  
Jiang-yi Long ◽  
Yi-jun Zhou ◽  
Bing-yu Liang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Dysfunction ◽  
Tanshinone Iia ◽  
Neurocognitive Disorder ◽  
Nissl Staining ◽  
Therapeutic Drugs ◽  
The Central Nervous System ◽  
Hiv Associated Neurocognitive Disorder ◽  
Cognition Impairment

Chemokine CC motif ligand 2 (CCL2) is one of the most recognized proinflammatory chemokines, and the expression of CCL2 in the cerebrospinal fluid of patients infected with HIV-1 is significantly higher than that of healthy people. As such, it is seen as an important cause of HIV-associated neurocognitive disorder (HAND). Our previous investigation has confirmed the pathological role of CCL2 in mediating brain damage leading to cognitive dysfunction. Currently, however, research on therapeutic drugs for the central nervous system targeting CCL2 is very limited. Our present study used brain stereotactic technology to induce cognitive impairment in rats by injecting CCL2 (5 ng) into the bilateral hippocampus. To investigate the protective effect and mechanism of Tanshinone IIA (25, 50, 75 mg/kg/d) on CCL2-induced learning memory and cognitive impairment in rats, we performed the Morris water maze (MWM) and novel object recognition tests (NORT) on the rats. The results showed that Tanshinone IIA significantly alleviated CCL2-induced learning memory and cognitive dysfunction. Further studies on the hippocampal tissue of the rats revealed that Tanshinone IIA treatment significantly increased the activity of SOD and GSH-Px while the level of MDA decreased compared to the model group. Additionally, the relative expression of apoptosis-associated genes caspase-3, caspase-8, and caspase-9 and inflammation-associated genes IL-1β and IL-6 in Tanshinone IIA-treated rats was lower than that in model rats. Finally, we confirmed hippocampal neuron loss and apoptosis by Nissl staining and TdT-mediated dUTP Nick end labeling (TUNEL). Taken together, these data imply that Tanshinone IIA can ameliorate CCL2-induced learning memory and cognitive impairment by impacting oxidative stress, inflammation, and apoptosis. Tanshinone IIA may be a potential therapeutic agent for the treatment of HAND.

Neurological Effects of HIV Infection

2019 ◽  
pp. 413-432
Author(s):  
Rodrigo Hasbun ◽  
Richard Dunham ◽  
Rituparna Das ◽  
Karen Nunez-Wallace ◽  
Lydia J. Sharp ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Severe Form ◽  
Viral Escape ◽  
Neurocognitive Disorder ◽  
The Central Nervous System ◽  
Hiv Associated Neurocognitive Disorder ◽  
Cns Penetration ◽  
Neurological Effects ◽  
Cns Penetration Effectiveness ◽  
Hiv Associated Neurocognitive Disorders

Discuss the clinical features, differential diagnosis, and management of HIV-associated neurocognitive disorders. • CD8+ T cell encephalitis has been described as a severe form of HIV-associated neurocognitive disorder (HAND). • The central nervous system (CNS) penetration effectiveness score has been correlated with cerebrospinal fluid (CSF) viral escape....

scholarly journals Neuroimaging of HIV-associated neurocognitive disorders

2015 ◽  
Vol 9 (4) ◽  
pp. 380-384 ◽  
Author(s):  
Michel Elyas Jung Haziot ◽  
Silas Pereira Barbosa Junior ◽  
José E. Vidal ◽  
Francisco Tomaz Meneses de Oliveira ◽  
Augusto César Penalva de Oliveira
Keyword(s):  
Cognitive Impairment ◽  
Neurocognitive Disorders ◽  
Classification Criteria ◽  
Neurocognitive Disorder ◽  
Aids Patients ◽  
Asymptomatic Neurocognitive Impairment ◽  
Associated Diseases ◽  
Broad Term ◽  
Cns Penetration ◽  
Hiv Associated Neurocognitive Disorders

ABSTRACT A significant increase in the incidence of cognitive impairment in HIV/AIDS patients has been continuously observed. Consequently, three classification categories of cognitive impairment have been proposed: asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND), that correspond to the mild and intermediate forms, and HIV-associated dementia (HAD) for the most severe cases. HIV-associated neurocognitive disorders (HAND) is a broad term that encompasses these three categories. Moreover, the application of neuroimaging methods has led to a major breakthrough in understanding of the neurological changes in HIV, providing greater reliability in the exclusion of associated diseases and allowing earlier diagnosis. Therefore, abnormalities and/or specific neuroimaging elements may soon be incorporated into the HAND classification criteria, which will be of great value in the management of these diseases, including in the optimization of high CNS penetration antiretroviral regimens.

scholarly journals Scaling Up Information Sharing on HIV-Associated Neurocognitive Disorder: Raising Awareness and Knowledge Among Key Stakeholders

SAGE Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 215824402110168
Author(s):  
Renato M. Liboro ◽  
Paul A. Shuper ◽  
Lori E. Ross
Keyword(s):  
Health Care ◽  
Information Sharing ◽  
Service Providers ◽  
Scale Up ◽  
People Living With Hiv ◽  
Neurocognitive Disorder ◽  
Public Health Informatics ◽  
Raising Awareness ◽  
Hiv Associated Neurocognitive Disorder ◽  
Hiv Aids

Although the majority of specialists and researchers in the field of HIV/AIDS are aware and knowledgeable about HIV-associated neurocognitive disorder (HAND) as a condition that affects as much as 50% of people living with HIV/AIDS (PLWH), research has documented that many health care and service providers who work directly with PLWH are either unaware of HAND or believe they do not know enough information about HAND to effectively support their clients experiencing neurocognitive challenges. Based on the findings of a qualitative study that interviewed 33 health care and service providers in HIV/AIDS services to identify and examine their awareness and knowledge on HAND, this article argues for utilizing a combination of Public Health Informatics principles; communication techniques, propagation strategies, and recognized approaches from Implementation and Dissemination Science; and social media and online discussion platforms, in addition to traditional Knowledge Mobilization strategies, to scale up information sharing on HAND among all relevant stakeholders. Increasing information sharing among stakeholders would be an important step to raising awareness and knowledge on HAND, and consequently, improving care, services, and support for PLWH and neurocognitive issues.

Genetic variation of matrix metalloproteinase enzyme in HIV-associated neurocognitive disorder

Gene ◽  
2019 ◽  
Vol 698 ◽  
pp. 41-49 ◽  
Author(s):  
HariOm Singh ◽  
Sumitra Nain ◽  
Asha Krishnaraj ◽  
Sonam Lata ◽  
T.N. Dhole
Keyword(s):  
Genetic Variation ◽  
Matrix Metalloproteinase ◽  
Neurocognitive Disorder ◽  
Hiv Associated Neurocognitive Disorder

Effects of a 12-week aerobic exercise programme on HIV-associated neurocognitive disorder in Nigeria: A protocol for randomized controlled trial (Preprint)

2021 ◽  
Author(s):  
Martins Nweke ◽  
Nombeko Mshunqane ◽  
Nalini Govender ◽  
Aderonke Akineplu ◽  
Adesola Oginniyi
Keyword(s):  
Aerobic Exercise ◽  
Repeated Measures ◽  
Controlled Trial ◽  
Exercise Programme ◽  
Moderate Intensity ◽  
Behavioural Intervention ◽  
Neurocognitive Disorder ◽  
Neurocognitive Performance ◽  
Southeastern Nigeria ◽  
Hiv Associated Neurocognitive Disorder

BACKGROUND The introduction of antiretroviral therapy (ART) has led to a drastic fall in the incidence of HIV-associated dementia. However, less severe but limiting forms of HIV-associated neurocognitive disorder (HAND) continues to be prevalent even with the use of ART. Aerobic exercise, a behavioural intervention may be a beneficial and effective complement to ART in the management of HAND. In HIV-negative individuals, aerobic exercise mitigates pathogenic changes similar to those of HAND. OBJECTIVE This protocol describes a randomized clinical trial designed to determine the effect of a 12-week aerobic exercise programme on HAND in Southeastern Nigeria. METHODS A minimum of seventy-six patients diagnosed with HAND will be randomized into aerobic exercise and control groups. Aerobic exercise will be carried out on a stationary bicycle ergometer at moderate intensity, three times a week for 12-weeks. Primary outcomes are neurocognitive performance, CD4-count and viral load. Evaluation of post-exercise neurocognitive performance will be undertaken using reliable neuropsychological tests relevant to PLWHIV, in line with Frascati criteria. Secondary outcomes such as quality of life, and activity limitation and social participation will be assessed using the WHOQOL-Bref, and the Oxford Participation and Activities questionnaire respectively. Data will be subjected to exploratory statistics to test for normality and homogeneity. The effect of the exercise programme on HAND will be analysed using two-way repeated-measures ANOVA, with Bonferroni’s correction. Within-group comparison will be undertaken using paired sampled t-test. RESULTS Enrollment began on 18th January 2021. Recruitment has been completed. The trial is ongoing and will be completed in July 2021 CONCLUSIONS The study will provide valuable information about the effect of aerobic exercise on HAND thus verifying the suitability of aerobic exercise as a complementary therapy for mitigating neurocognitive disorder among PLWHIV. Data from the study will be useful in pursuit of debate on the necessity of a sponsored rehabilitation arm in ART clinics. CLINICALTRIAL The study was registered with the PAN African Trial Registry (PACTR) on the 1stth September 2020. The registration ID is PACTR202009483415745.

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