Acute nicotine vapor normalizes sensorimotor gating and reduces locomotor activity deficits in HIV-1 transgenic rats.

Rationale: Despite improved life expectancy of people with HIV (PWH), HIV-associated neurocognitive impairment (NCI) persists, alongside deficits in sensorimotor gating and neuroinflammation. PWH exhibit high smoking rates, possibly due to neuroprotective, anti-inflammatory, and cognitive-enhancing effects of nicotine, suggesting potential self-medication. Objectives: Here, we tested the effects of acute nicotine vapor exposure on translatable measures of sensorimotor gating and exploratory behavior in the HIV-1 transgenic (HIV-1Tg) rat model of HIV. Methods: Male and female HIV-1Tg and F344 control rats (n=57) were exposed to acute nicotine or vehicle vapor. Sensorimotor gating was assessed using prepulse inhibition (PPI) of the acoustic startle response, and exploratory behavior was evaluated using the behavioral pattern monitor (BPM). Results: Vehicle-treated HIV-1Tg rats exhibited PPI deficits at low prepulse intensities compared to F344 controls, as seen previously. No PPI deficits were observed in nicotine-treated HIV1-Tg rats, however. HIV-1Tg rats were hypoactive in the BPM relative to controls, whilst nicotine vapor increased activity and exploratory behavior across genotypes. Cotinine analyses confirmed comparable levels of the primary metabolite of nicotine across genotypes. Conclusions: Previous findings of PPI deficits in HIV-1Tg rats were replicated and, importantly, attenuated by acute nicotine vapor. Evidence for similar cotinine levels suggest a nicotine-specific effect in HIV-1Tg rats. HIV-1Tg rats had reduced exploratory behavior compared to controls, attenuated by acute nicotine vapor. Therefore, acute nicotine may be beneficial for remediating sensorimotor and locomotor activity deficits in PWH. Future studies should determine the long-term effects of nicotine vapor on similar HIV/NCI-relevant behaviors.

Short-term exposure to HIV Tat induces glial activation and changes in perineuronal nets.

Despite widespread use of combination antiretroviral therapy (cART), there remains a subset of individuals who display cognitive impairment broadly known as HIV-associated neurocognitive disorder (HAND). Interestingly, HIV-infected cells continuously release the HIV-1 protein Tat even in the presence of cART. Persistent exposure to Tat is proposed to increase both neuroinflammation and neurotoxicity. In vitro evidence shows that matrix metalloproteinases (MMPs) are among the neuroinflammatory molecules induced by Tat, which are known to disrupt specialized neuronal extracellular matrix structures called perineuronal nets (PNNs). PNNs predominantly surround parvalbumin interneurons and help to buffer these cells from oxidant stress and to independently increase their excitability. In order to better understand the link between short-term exposure to Tat, neuroinflammation, and PNNs, we explored the direct effects of Tat on glial cells and neurons. Herein, we report that in mixed glial cultures, Tat directly increases the expression of proinflammatory molecules, including MMP-9. Moreover, direct injection of Tat protein into mouse hippocampus increases the expression of astrocyte and microglia markers as well as MMP-9. The number of PNNs is decreased following Tat exposure, followed later by decreased numbers of hippocampal parvalbumin-expressing neurons. In older mice, Tat induced significant increases in the gene expression of proinflammatory molecules including markers of gliosis, MMPs and complement system proteins. Taken together, these data support a direct effect of Tat on glial-derived MMP expression subsequently affecting PNNs and neuronal health, with older mice more susceptible to Tat-induced inflammation.

Glutathione in HIV-Associated Neurocognitive Disorders.

A large portion of patients with Human Immunodeficiency Virus (HIV) have neurologic sequelae. Those with better-controlled HIV via antiretroviral therapies generally have less severe neurologic symptoms. However, for many patients, antiretrovirals do not adequately resolve symptoms. Since much of the pathogenesis of HIV/AIDS (Autoimmune Deficiency Syndrome) involves oxidative stress either directly, through viral interaction, or indirectly, through inflammatory mechanisms, we have reviewed relevant trials of glutathione supplementation in each of the HIV-associated neurocognitive diseases and have found disease-specific results. For diseases for which trials have not been completed, predicted responses to glutathione supplementation are made based on relevant mechanisms seen in the literature. It is not sufficient to conclude that all HIV-associated neurocognitive disorders (HAND) will benefit from the antioxidant effects of glutathione supplementation. The potential effects of glutathione supplementation in patients with HAND are likely to differ based on the specific HIV-associated neurocognitive disease.

A longitudinal study of the brain structure network changes in HIV patients with ANI: combined VBM with SCN.

Background: Despite the widespread adoption of combination antiretroviral therapy (cART) in managing HIV, the virus's impact on the brain structure of patients remains significant. This study aims to longitudinally explore the persistent effects of HIV on brain structure, focusing on changes in gray matter volume (GMV) and structural covariance network (SCN) among patients at the Asymptomatic Neurocognitive Impairment (ANI) stage. Methods: This research involved 45 HIV patients diagnosed with ANI and 45 demographically matched healthy controls (HCs). The participants were observed over a 1.5-year period. Differences in GMV between groups were analyzed using voxel-based morphometry (VBM), while the graph theory model facilitated the establishment of topological metrics for assessing network indices. These differences were evaluated using two-sample t-tests and paired-sample t-tests, applying the network-based statistics method. Additionally, the study examined correlations between GMV and cognitive performance, as well as clinical variables. Results: Compared with HCs, HIV patients demonstrated reduced GMV in the right middle temporal gyrus and left middle frontal gyrus (FWE, p < 0.05), along with decreased betweenness centrality (BC) in the left anterior cingulate and paracingulate cortex. Conversely, an increase in the clustering coefficient (Cp) was observed (FDR, p < 0.05). During the follow-up period, a decline in GMV in the right fusiform gyrus (FWE, p < 0.05) and a reduction in node efficiency (Ne) in the triangular part of the inferior frontal gyrus were noted compared with baseline measurements (FDR, p < 0.05). The SCN of HIV patients exhibited small-world properties across most sparsity levels (Sigma >1), and area under the curve (AUC) analysis revealed no significant statistical differences between groups. Conclusion: The findings suggest that despite the administration of combination antiretroviral therapy (cART), HIV continues to exert slow and sustained damage on brain structures. However, when compared to HCs, the small-world properties of the patients' SCNs did not significantly differ, and the clustering coefficient, indicative of the overall information-processing capacity of the brain network, was slightly elevated in HIV patients. This elevation may relate to compensatory effects of brain area functions, the impact of cART, functional reorganization, or inflammatory responses.

1H-NMR metabolomics investigation of CSF from children with HIV reveals altered neuroenergetics due to persistent immune activation.

Background: HIV can invade the central nervous system (CNS) early during infection, invading perivascular macrophages and microglia, which, in turn, release viral particles and immune mediators that dysregulate all brain cell types. Consequently, children living with HIV often present with neurodevelopmental delays. Methods: In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to analyze the neurometabolic profile of HIV infection using cerebrospinal fluid samples obtained from 17 HIV+ and 50 HIV- South African children. Results: Nine metabolites, including glucose, lactate, glutamine, 1,2-propanediol, acetone, 3-hydroxybutyrate, acetoacetate, 2-hydroxybutyrate, and myo-inositol, showed significant differences when comparing children infected with HIV and those uninfected. These metabolites may be associated with activation of the innate immune response and disruption of neuroenergetics pathways. Conclusion: These results elucidate the neurometabolic state of children infected with HIV, including upregulation of glycolysis, dysregulation of ketone body metabolism, and elevated reactive oxygen species production. Furthermore, we hypothesize that neuroinflammation alters astrocyte-neuron communication, lowering neuronal activity in children infected with HIV, which may contribute to the neurodevelopmental delay often observed in this population.

Awareness and Knowledge of HIV-Associated Neurocognitive Disorder Among Middle-Aged and Older People Living With HIV/AIDS in Southern Nevada: Implications for HIV/AIDS Community-Based Education Programs.

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.

Autophagy Deregulation in HIV-1-Infected Cells Increases Extracellular Vesicle Release and Contributes to TLR3 Activation.

Human immunodeficiency virus type 1 (HIV-1) infection can result in HIV-associated neurocognitive disorder (HAND), a spectrum of disorders characterized by neurological impairment and chronic inflammation. Combined antiretroviral therapy (cART) has elicited a marked reduction in the number of individuals diagnosed with HAND. However, there is continual, low-level viral transcription due to the lack of a transcription inhibitor in cART regimens, which results in the accumulation of viral products within infected cells. To alleviate stress, infected cells can release accumulated products, such as TAR RNA, in extracellular vesicles (EVs), which can contribute to pathogenesis in neighboring cells. Here, we demonstrate that cART can contribute to autophagy deregulation in infected cells and increased EV release. The impact of EVs released from HIV-1 infected myeloid cells was found to contribute to CNS pathogenesis, potentially through EV-mediated TLR3 (Toll-like receptor 3) activation, suggesting the need for therapeutics to target this mechanism. Three HIV-1 TAR-binding compounds, 103FA, 111FA, and Ral HCl, were identified that recognize TAR RNA and reduce TLR activation. These data indicate that packaging of viral products into EVs, potentially exacerbated by antiretroviral therapeutics, may induce chronic inflammation of the CNS observed in cART-treated patients, and novel therapeutic strategies may be exploited to mitigate morbidity.

HIV associated neurocognitive disorder screening and diagnosis pathways in Australia: a scoping review and international implications.

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.

Mindfulness-Based Stress Reduction for Symptom Management in Older Individuals with HIV-Associated Neurocognitive Disorder.

The growing number of people aging with HIV represents a group vulnerable to the symptom burdens of HIV-associated neurocognitive disorder (HAND). Among younger groups, Mindfulness-Based Stress Reduction (MBSR) has been shown to help people living with HIV manage HIV-related and other life stress, and although there is some theoretical and empirical evidence that it may be effective among those with cognitive deficits, the approach has not been studied in older populations with HAND. Participants (n = 180) 55 years or older with HIV and cognitive impairment were randomly assigned to either an 8-week MBSR arm or a waitlist control. We assessed the impact of MBSR compared to a waitlist control on psychological outcomes [stress, anxiety, depression, and quality of life (QOL)] and cognitive metrics (e.g., speed of information processing, working memory, attention, impulsivity) measured at baseline, immediately post intervention (8 weeks) and one month later (16 weeks). Intent to treat analyses showed significant improvement in the MBSR group compared to control on symptoms of depression from baseline to 8 weeks, however, the difference was not sustained at 16 weeks. The MBSR group also showed improvement in perceived QOL from baseline to 16 weeks compared to the waitlist control group. Cognitive performance did not differ between the two treatment arms. MBSR shows promise as a tool to help alleviate the symptom burden of depression and low QOL in older individuals living with HAND and future work should address methods to better sustain the beneficial impact on depression and QOL.

Cognitive Impairment in People Living with HIV and the Impact of Mood: Results from a Cross-Sectional Study.

Background: Human Immunodeficiency Virus (HIV) infection represents a significant public health concern and, consequently, the incidence of HIV-Associated Neurocognitive Disorder (HAND) has grown over the years. The present study aims to assess HAND with the Montreal Cognitive Assessment (MoCA) in People Living With HIV/AIDS (PLWHA) to find significant associations with cognitive impairment. Methods: The study included 210 PLWHA, aged from 30 to 81 years, of whom, 137 (65.2%) were males. They were assessed at the Immunology Service of the University Hospital of Monserrato, Cagliari, Italy, between November 2022 and April 2023. Results: The sample showed an overall optimal response to antiretroviral therapy, as shown by the excellent levels of CD4+ lymphocytes and HIV RNA copies. A sum of 115 subjects (54.8%) were considered cognitively impaired and the multivariate analysis demonstrated that it was independently associated with duration of infection (OR: 0.96), age (OR: 1.12), alanine aminotransferase (ALT) (OR: 1.02), and depression (OR: 1.33). By dichotomizing the variables, the significance of the association was confirmed for age (65-year threshold) (χ2: 5.142, p = 0.0233) and depression (χ2: 7.834, p = 0.0051). Conclusions: Our study demonstrates that it is hard to find both statistically and clinically significantly associated variables with cognitive impairment in PLWHA, and that the strongest independent association is with depressed mood.

Antiretroviral drugs from multiple classes induce loss of excitatory synapses between hippocampal neurons in culture.

Introduction: Antiretroviral (ARV) drugs have improved prognoses for people living with HIV. However, HIV-associated neurocognitive disorders (HAND) persist despite undetectable viral loads. Some ARVs have been linked to neuropsychiatric effects that may contribute to HAND. Synapse loss correlates with cognitive decline in HAND and synaptic deficits may contribute to the neuropsychiatric effects of ARV drugs. Methods: Using an automated high content assay, rat hippocampal neurons in culture expressing PSD95-eGFP to label glutamatergic synapses and mCherry to fill neuronal structures were imaged before and after treatment with 25 clinically used ARVs. Results and Discussion: At a concentration of 10 µM the protease inhibitors nelfinavir and saquinavir, the non-nucleoside reverse transcriptase inhibitors etravirine and the 8-OH metabolite of efavirenz, the integrase inhibitor bictegravir, and the capsid inhibitor lenacapavir produced synaptic toxicity. Only lenacapavir produced synapse loss at the nanomolar concentrations estimated free in the plasma, although all 4 ARV drugs induced synapse loss at Cmax. Evaluation of combination therapies did not reveal synergistic synaptic toxicity. Synapse loss developed fully by 24 h and persisted for at least 3 days. Bictegravir-induced synapse loss required activation of voltage-gated Ca2+ channels and bictegravir, etravirine, and lenacapavir produced synapse loss by an excitotoxic mechanism. These results indicate that select ARV drugs might contribute to neuropsychiatric effects in combination with drugs that bind serum proteins or in disease states in which synaptic function is altered. The high content imaging assay used here provides an efficient means to evaluate new drugs and drug combinations for potential CNS toxicity.

A critical role for Macrophage-derived Cysteinyl-Leukotrienes in HIV-1 induced neuronal injury.

Macrophages (MΦ) infected with human immunodeficiency virus (HIV)-1 or activated by its envelope protein gp120 exert neurotoxicity. We found previously that signaling via p38 mitogen-activated protein kinase (p38 MAPK) is essential to the neurotoxicity of HIVgp120-stimulated MΦ. However, the associated downstream pathways remained elusive. Here we show that cysteinyl-leukotrienes (CysLT) released by HIV-infected or HIVgp120 stimulated MΦ downstream of p38 MAPK critically contribute to neurotoxicity. SiRNA-mediated or pharmacological inhibition of p38 MAPK deprives MΦ of CysLT synthase (LTC4S) and, pharmacological inhibition of the cysteinyl-leukotriene receptor 1 (CYSLTR1) protects cerebrocortical neurons against toxicity of both gp120-stimulated and HIV-infected MΦ. Components of the CysLT pathway are differentially regulated in brains of HIV-infected individuals and a transgenic mouse model of NeuroHIV (HIVgp120tg). Moreover, genetic ablation of LTC4S or CysLTR1 prevents neuronal damage and impairment of spatial memory in HIVgp120tg mice. Altogether, our findings suggest a novel critical role for cysteinyl-leukotrienes in HIV-associated brain injury.

Interferon-ß deficiency alters brain response to chronic HIV-1 envelope protein exposure in a transgenic model of NeuroHIV.

Human immunodeficiency virus-1 (HIV-1) infects the central nervous system (CNS) and causes HIV-associated neurocognitive disorders (HAND) in about half of the population living with the virus despite combination anti-retroviral therapy (cART). HIV-1 activates the innate immune system, including the production of type 1 interferons (IFNs) α and ß. Transgenic mice expressing HIV-1 envelope glycoprotein gp120 (HIVgp120tg) in the CNS develop memory impairment and share key neuropathological features and differential CNS gene expression with HIV patients, including the induction of IFN-stimulated genes (ISG). Here we show that knocking out IFNß (IFNßKO) in HIVgp120tg and non-tg control mice impairs recognition and spatial memory, but does not affect anxiety-like behavior, locomotion, or vision. The neuropathology of HIVgp120tg mice is only moderately affected by the KO of IFNß but in a sex-dependent fashion. Notably, in cerebral cortex of IFNßKO animals presynaptic terminals are reduced in males while neuronal dendrites are reduced in females. The IFNßKO results in the hippocampal CA1 region of both male and female HIVgp120tg mice in an ameliorated loss of neuronal presynaptic terminals but no protection of neuronal dendrites. Only female IFNß-deficient HIVgp120tg mice display diminished microglial activation in cortex and hippocampus and increased astrocytosis in hippocampus compared to their IFNß-expressing counterparts. RNA expression for some immune genes and ISGs is also affected in a sex-dependent way. The IFNßKO abrogates or diminishes the induction of MX1, DDX58, IRF7 and IRF9 in HIVgp120tg brains of both sexes. Expression analysis of neurotransmission related genes reveals an influence of IFNß on multiple components with more pronounced changes in IFNßKO females. In contrast, the effects of IFNßKO on MAPK activities are independent of sex with pronounced reduction of active ERK1/2 but also of active p38 in the HIVgp120tg brain. In summary, our findings show that the absence of IFNß impairs memory dependent behavior and modulates neuropathology in HIVgp120tg brains, indicating that its absence may facilitate development of HAND. Moreover, our data suggests that endogenous IFNß plays a vital role in maintaining neuronal homeostasis and memory function.

Crosstalk between gut microbiome and neuroinflammation in pathogenesis of HIV-associated neurocognitive disorder.

HIV-associated neurocognitive disorder (HAND) has become a chronic neurodegenerative disease affecting the quality of life in people living with HIV (PLWH). Despite an established association between HAND and neuroinflammation induced by HIV proteins (gp120, Tat, Rev., Nef, and Vpr), the pathogenesis of HAND remains to be fully elucidated. Accumulating evidence demonstrated that the gut microbiome is emerging as a critical regulator of various neurodegenerative diseases (e.g., Parkinson's disease, Alzheimer's disease), suggesting that the crosstalk between the gut microbiome and neuroinflammation may contribute to the development of these diseases, for example, gut dysbiosis and microbiota-derived metabolites can trigger inflammation in the brain. However, the potential role of the gut microbiome in the pathogenesis of HAND remains largely unexplored. In this review, we aim to discuss and elucidate the HAND pathogenesis correlated with gut microbiome and neuroinflammation, and intend to explore the probable intervention strategies for HAND.

Altered metabolism in right basal ganglia associated with asymptomatic neurocognitive impairment in HIV-infected individuals.

Background: Only few studies have focused on the metabolite differences between asymptomatic neurocognitive impairment (ANI) and cognitively normal people living with HIV (PLWH). The current study aims to examine whether brain metabolisms in basal ganglia (BG) by magnetic resonance spectroscopy (MRS) were potential to discriminate ANI from cognitively normal PLWH. Methods: According to neuropsychological (NP) test, 80 PLWH (37.4 ± 10.2 years) were divided into ANI group (HIV-ANI, n = 31) and NP normal group (HIV-normal, n = 49). Brain metabolisms by MRS from right BG were compared between groups, including N-acetylaspartate and N-acetyl aspartylglutamate (tNAA), creatine and phosphocreatine (tCr), and choline-containing compounds (tCho). A total value of three metabolites were introduced. All brain metabolisms were evaluated as its percentage of total. Furthermore, correlations between MRS and NP and clinical measures were evaluated. A logistic regression model was applied, and the AUC values for the model and the continuous factors were compared using receiver operating curve (ROC) analysis. Results: Compared to HIV-normal group, tNAA/total was lower and tCr/total was higher in the HIV-ANI group (P < 0.05). Both tNAA/total and tCr/total values were correlated with NP score (P < 0.05), especially in verbal fluency, speed of information processing, learning, and recall (P < 0.05). The logistic model included BG-tCr/total, current CD4 and infection years of PLWH. The AUC value for the BG-tCr/total was 0.696 and was not significantly lower than that for logistic model (P < 0.01). Conclusion: The altered brain metabolites in the right BG were found in the ANI group compared to PLWH with normal cognition, and further associated with NP deficits. The current findings indicated that brain metabolites assessed by MRS has the potential to discriminate ANI from cognitively normal PLWH.

A 2-year longitudinal randomized controlled trial examining the transfer of speed of processing training to secondary cognitive domains in middle-aged and older adults with HIV-associated neurocognitive disorder: Results of the think fast study.

OBJECTIVE: As people with HIV (PWH) age, they are at-risk of developing cognitive impairments compared to their seronegative counterparts. Although speed of processing (SOP) training may help improve this cognitive ability, less work has examined transfer to other cognitive domains. This study examined the effect of SOP training has on secondary cognitive domains in PWH aged 40+ years. METHOD: In this 3-group 2-year longitudinal study, 216 PWH with HIV-associated neurocognitive disorder (HAND) or borderline HAND were randomized to either: (1) 10 h of SOP training (n = 70); (2) 20 h of SOP training (n = 73); or (3) 10 h of an active control training (n = 73). Participants completed a comprehensive cognitive battery at baseline, immediately after training, and at 1 and 2 years. This battery yielded global and domain specific T-scores as well as a cognitive impairment variable. Generalized linear mixed-effect models were fitted to estimate between-group mean differences at the follow-up time-points adjusted for baseline. RESULTS: No clinically or statistically significant improvements in any of the cognitive outcomes were observed. A sensitivity analysis was conducted; conclusions replicated those of the main analysis, with two exceptions: Global Function T and Psychomotor Speed T showed relevant training improvements among the intervention groups over the control group at the immediate post time point. CONCLUSIONS: Although SOP training has been shown to improve cognitive abilities that correspond to driving and mobility, such training has limited therapeutic utility in improving cognition in other domains in PWH with HAND.

Factors associated with neurocognitive impairment in treatment experienced HIV+ Adults: A perspective from a Tertiary Care Center in Ethiopia: factors associated with HAND in Ethiopia

Background: Given the improvement in life expectancy of people living with HIV (PLWH) in sub-Saharan Africa, the risk of asymptomatic HIV-associated neurocognitive disorder (HAND) has increased. The study objectives were to investigate the prevalence of HAND and associated factors among treatment experienced adults in Ethiopia. Methods: A single-center observational cross-sectional study was conducted between December 2019 and June2020 to investigate HAND. International HIV dementia scale (IHDS) was used to screen for the disorder. Both descriptive and analytical statistics were used to analyze the data. Results: Total of 324 PLWH (63% females) who were on combination antiretroviral therapy for median of 144months (IQR: 108-168) were investigated. The mean age was 42.5 years (1SD=12.2). The prevalence of HAND was 75.3% and the difference was significantly more in those above 40 years of age (65.8% vs. 80.7%, p=0.003). Age is the only risk factor identified with multivariable logistic regression analysis. A linear decrement in the total score of cognitive performance was observed as the patient's age increase; age was responsible for 9.4% variation observed in IHDS score (r= -0.31, R2=0.094, p<0.0001). Although statistically not-significant, the trend for cardio-metabolic and behavioral risk factors (hypertension, diabetes mellitus, dyslipidemia, smoking, alcohol and khat use) was higher in the group diagnosed with HAND. Conclusion: The occurrence of neurocognitive impairment was more pronounced in individuals aged 40 years and above who were HIV positive, compared to those below 40 years. Age was found to be an independent predictor of HAND. Cardiovascular and behavioral risk factors were observed more among patients with HAND compared to no-HAND

Functions of HIV-1 Tat and its association with diseases / 中国生物制品学杂志

@#Acquired immune deficiency syndrome,or AIDS,has been a major infectious disease that troubles the public health in a global scale. Human immunodeficiency virus type 1(HIV-1)is the causative reagent responsible for AIDS development. Even though the highly active anti-retroviral therapy(HAART,or the cocktail therapy)that has been widely applied could effectively suppress the infection and replication of HIV-1,the infected people suffer from other related diseases,such as the HIV-associated neurocognitive disorder(HAND). This paper mainly focused on the function of an important regulatory protein of HIV-1,trans-activator of transcription(Tat),and its correlation with HIV-1 replication and HAND development,so as to clarify the importance of developing anti-AIDS drugs targeting Tat protein

Brain computed tomography perfusion analysis in HIV-seropositive adults with and without neurocognitive impairment in Nigeria: outcomes and challenges of a pilot study.

Introduction: the significance of cerebrovascular disease in HIV-associated neurocognitive disorder (HAND) in a homogeneous black population has not yet been determined. This incident case-control study used CT perfusion imaging to quantify and compare regional cerebral blood flow parameters in neuro-cognitively impaired and unimpaired HIV+ participants of the Ibadan Cohort on Neuro AIDS (ICON) in Nigeria. Methods: this was an incident case-control study consisting of twenty-seven HIV+ adults, classified based on Frascati criteria into neurocognitive impaired (n=18) and unimpaired (n=9) groups, who had brain computed tomographic perfusion (CTP) with a 64-slice Toshiba T scanner. The standard deviation (SD) of regional mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume (CBV) values were calculated for bilateral basal ganglia (BG), frontal, parietal, temporal, and occipital regions from CT perfusion maps. The regional mean values and variability (SD) in the CTP measures were compared in the groups using an independent student t-test. Results: differentially higher variability in the bilateral CBF measures in the parietal (right; OR = 1.14, x̄ =5.61, p=0.041, CI=0.27-11.35/left; OR = 1.16, x̄=7.01, p=0.03, CI=5.6-13.47) and time to peak (TTP) measures in the basal ganglia (right; OR = 3.78, x̄=0.88, p=0.032, CI=0.081-1.67/left; OR = 2.44, x̄=1.48, p=0.020, CI=0.26-2.71) and occipital (right; OR = 2.18, x̄=1.32, p=0.018, CI=0.25-2.38/left; OR = 1.93, x̄=1.08, p=0.034, CI=0.086-2.06) regions were observed in the cognitively impaired group compared to the unimpaired group. Conclusion: the study evidence suggests that alterations in cerebral perfusion implicated in HIV-associated neurocognitive disorder may be possibly demonstrated using CTP, a readily available resource in most African countries saddled with the highest burden of HIV.

HIV-1 infection of genetically engineered iPSC-derived central nervous system-engrafted microglia in a humanized mouse model.

IMPORTANCE: Our mouse model is a powerful tool for investigating the genetic mechanisms governing central nervous system (CNS) human immunodeficiency virus type-1 (HIV-1) infection and latency in the CNS at a single-cell level. A major advantage of our model is that it uses induced pluripotent stem cell-derived microglia, which enables human genetics, including gene function and therapeutic gene manipulation, to be explored in vivo, which is more challenging to study with current hematopoietic stem cell-based models for neuroHIV. Our transgenic tracing of xenografted human cells will provide a quantitative medium to develop new molecular and epigenetic strategies for reducing the HIV-1 latent reservoir and to test the impact of therapeutic inflammation-targeting drug interventions on CNS HIV-1 latency.