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J Acquir Immune Defic Syndr 2022 05;90(1):106-114

HIV Neurobehavioral Research Center, University of California, San Diego, CA.

Background: We hypothesized that the induction of monocyte activation biomarkers, especially soluble urokinase-type plasminogen activator receptor (suPAR) and interferon γ-inducible protein 10 (IP-10), is lower in HIV-1C than HIV-1B, owing to a defective Tat cysteine dimotif (C30S).

Methods: A total of 68 paired cerebrospinal fluid (CSF) and blood samples from people with HIV (PWH), free of CNS opportunistic infections, from a Southern Brazil outpatient HIV clinic were evaluated such as HIV-1B subtype (n = 27), HIV-1C (n = 26), other (n = 15), and 19 HIV-negative controls. The levels of suPAR, IP-10, neopterin, and β2 microglobulin (β2m) in the CSF and serum were quantified using different immunoassays. Read More

BMC Neurol 2021 Dec 22;21(1):494. Epub 2021 Dec 22.

Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-415 50, Gothenburg, Sweden.

Background: Blood-brain barrier (BBB) injury is prevalent in patients with HIV-associated dementia (HAD) and is a frequent feature of HIV encephalitis. Signs of BBB damage are also sometimes found in neuroasymptomatic HIV-infected individuals without antiretroviral therapy (ART). The aim of this study was to investigate the integrity of the BBB before and after initiation of ART in both neuroasymptomatic HIV infection and in patients with HAD. Read More

Pharmacol Ther 2022 06 27;234:108047. Epub 2021 Nov 27.

Oklahoma State University Center for Health Sciences, School of Biomedical Science, 1111 West 17(th) Street, Tulsa, OK 74107-1898, USA. Electronic address:

As our understanding of changes to the neurological system has improved, it has become clear that patients who have contracted human immunodeficiency virus type 1 (HIV-1) can potentially suffer from a cascade of neurological issues, including neuropathy, dementia, and declining cognitive function. The progression from mild to severe symptoms tends to affect motor function, followed by cognitive changes. Central nervous system deficits that are observed as the disease progresses have been reported as most severe in later-stage HIV infection. Read More

J Neurosci 2021 12 11;41(50):10365-10381. Epub 2021 Nov 11.

Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58202-9037

Neurotoxic HIV-1 viral proteins contribute to the development of HIV-associated neurocognitive disorder (HAND), the prevalence of which remains high (30-50%) with no effective treatment available. Estrogen is a known neuroprotective agent; however, the diverse mechanisms of estrogen action on the different types of estrogen receptors is not completely understood. In this study, we determined the extent to which and mechanisms by which 17α-estradiol (17αE2), a natural less-feminizing estrogen, offers neuroprotection against HIV-1 gp120-induced neuronal injury. Read More

Viruses 2021 09 21;13(9). Epub 2021 Sep 21.

Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.

The neurovascular units (NVU) are the minimal functional units of the blood-brain barrier (BBB), composed of endothelial cells, pericytes, astrocytes, microglia, neurons, and the basement membrane. The BBB serves as an important interface for immune communication between the brain and peripheral circulation. Disruption of the NVU by the human immunodeficiency virus-1 (HIV-1) induces dysfunction of the BBB and triggers inflammatory responses, which can lead to the development of neurocognitive impairments collectively known as HIV-1-associated neurocognitive disorders (HAND). Read More

Sci Rep 2021 09 16;11(1):18519. Epub 2021 Sep 16.

Institute of Human Virology, Baltimore, MD, 21201, USA.

The combined antiretroviral therapy era has significantly increased the lifespan of people with HIV (PWH), turning a fatal disease to a chronic one. However, this lower but persistent level of HIV infection increases the susceptibility of HIV-associated neurocognitive disorder (HAND). Therefore, research is currently seeking improved treatment for this complication of HIV. Read More

Mediators Inflamm 2021 25;2021:1267041. Epub 2021 Aug 25.

Division of Molecular Biology, National AIDS Research Institute (ICMR-NARI), 73, G Block, MIDC, Bhosari, Post Box No. 1895, Pune, 411026 Maharashtra, India.

HIV-1 can incite activation of chemokine receptors, inflammatory mediators, and glutamate receptor-mediated excitotoxicity. The mechanisms associated with such immune activation can disrupt neuronal and glial functions. HIV-associated neurocognitive disorder (HAND) is being observed since the beginning of the AIDS epidemic due to a change in the functional integrity of cells from the central nervous system (CNS). Read More

Curr HIV/AIDS Rep 2021 10 24;18(5):459-474. Epub 2021 Aug 24.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.

Purpose Of Review: Involvement of the central nervous system (CNS) in HIV-1 infection is commonly associated with neurological disorders and cognitive impairment, commonly referred to as HIV-associated neurocognitive disorders (HAND). Severe and progressive neurocognitive impairment is rarely observed in the post-cART era; however, asymptomatic and mild neurocognitive disorders still exist, despite viral suppression. Additionally, comorbid conditions can also contribute to the pathogenesis of HAND. Read More

J Neuroimmunol 2021 09 30;358:577649. Epub 2021 Jun 30.

Department of Psychiatry and Mental Health, Brain Behaviour Unit, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

HIV-1 is responsible for the development of a spectrum of cognitive impairments known as HIV-associated neurocognitive disorder (HAND). In the era of antiretroviral therapy (ART), HAND remains prevalent in people living with HIV (PLWH), despite low or undetectable viral loads. Persistent neuroinflammation likely plays an important role in the contributing biological mechanisms. Read More

Mol Neurobiol 2021 Nov 13;58(11):5421-5436. Epub 2021 May 13.

Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, 1011 NW 15th Street, Miami, FL, 33136, USA.

Maintaining an intact pool of neural progenitor cells (NPCs) is crucial for generating new and functionally active neurons. Methamphetamine (METH) can exacerbate the HIV-induced deficit of adult neurogenesis; however, potential mechanisms of this influence are still poorly understood. In the present study, we present evidence that chronic exposure to METH combined with brain infection by EcoHIV results in enhanced proliferation of NPCs in the subventricular zone (SVZ) in mice. Read More

Autophagy 2021 07 23;17(7):1768-1782. Epub 2021 Apr 23.

Molecular Studies of Neurodegenerative Diseases Lab, FELS Cancer Institute for Personalized Medicine and Department of Neurology Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.

Despite the promising therapeutic effects of combinatory antiretroviral therapy (cART), 20% to 30% of HIV/AIDS patients living with long term infection still exhibit related cognitive and motor disorders. Clinical studies in HIV-infected patients revealed evidence of basal ganglia dysfunction, tremors, fine motor movement deficits, gait, balance, and increased risk of falls. Among older HIV adults, the frequency of cases with SNCA/α-synuclein staining is higher than in older healthy persons and may predict an increased risk of developing a neurodegenerative disease. Read More

J Neuroimmunol 2021 06 8;355:577542. Epub 2021 Mar 8.

HIV Neurobehavioral Research Center, University of California, San Diego, San Diego, CA, USA.

We hypothesized that humoral immunity stimulation in the CNS in HIV-1C patients would be lower than that in HIV-1B due to a defective Tat chemokine dimotif (C30C31) that might influence cellular trafficking and CNS inflammation. Sixty-eight paired CSF and blood samples from people with HIV (PWH), free of CNS opportunistic infections, were included, HIV-1B (n = 27), HIV-1C (n = 26), and HIV negative (n = 25). IgG intrathecal synthesis was assayed using quantitative and qualitative methods. Read More

J Neurovirol 2021 04 1;27(2):279-301. Epub 2021 Mar 1.

Axe Des Maladies Infectieuses Et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Pavillon CHUL, Quebec, QC, G1V 4G2, Canada.

HIV-1 infection in the central nervous system (CNS) causes the release of neurotoxic products from infected cells which trigger extensive neuronal loss. Clinically, this results in HIV-1-associated neurocognitive disorders (HAND). However, the effects on neuroprotective factors in the brain remain poorly understood and understudied in this situation. Read More

Neurosci Lett 2021 04 12;750:135717. Epub 2021 Feb 12.

Department of Psychology and Neuroscience, University of North Carolina, Chapel Hill, NC, 27599, USA. Electronic address:

In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is considered a chronic disease with an inflammatory component that specifically targets the brain and causes a high prevalence of HIV-1-associated neurocognitive disorders (HAND). The endocannabinoid (eCB) system has attracted interest as a target for treatment of neurodegenerative disorders, due to the potential anti-inflammatory and neuroprotective properties of cannabinoids, including its potential therapeutic use in HIV-1 neuropathogenesis. In this review, we summarize what is currently known about the structural and functional changes of the eCB system under conditions of HAND. Read More

J Neurochem 2021 05 22;157(3):429-449. Epub 2021 Jan 22.

Human Metabolomics, North-West University, Potchefstroom, South Africa.

HIV-associated neurocognitive disorders (HAND) are common features of the effect of human immunodeficiency virus (HIV)-1 within the central nervous system (CNS). The underlying neuropathophysiology of HAND is incompletely known. Furthermore, there are no markers to effectively predict or stratify the risk of HAND. Read More

J Acquir Immune Defic Syndr 2021 04;86(4):496-499

Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.

Background: Systemic immune activation and inflammation in chronic HIV infection are driving factors of non-AIDS-related events, including neurocognitive impairment. The role of inflammasome in monocytes from patients with HIV infection has been extensively studied, but its association with the extent of neurocognitive dysfunction has been poorly investigated.

Methods: We enrolled 79 HIV-positive patients; 44 with varying levels of HIV-associated neurocognitive disorder (HAND) and 35 without and 8 healthy donors. Read More

Retrovirology 2020 11 19;17(1):35. Epub 2020 Nov 19.

Division of Infectious Diseases, Cincinnati Children's Hospital, 3333 Burnet Avenue, MLC 7017, Cincinnati, OH, 45229, USA.

Background: HIV associated neurocognitive disorders cause significant morbidity and mortality despite the advent of highly active antiretroviral therapy. A deeper understanding of fundamental mechanisms underlying HIV infection and pathogenesis in the central nervous system is warranted. Microglia are resident myeloid cells of the brain that are readily infected by HIV and may constitute a CNS reservoir. Read More

J Neuroimmune Pharmacol 2021 06 29;16(2):238-250. Epub 2020 Oct 29.

Department of Neuroscience and Center for Neurovirology, Temple University Lewis Katz School of Medicine, 3500 North Broad Street, Medical Education and Research Building Room 753, 7th Floor, Philadelphia, PA, 19140, USA.

Despite adherence to treatment, individuals living with HIV have an increased risk for developing cognitive impairments, referred to as HIV-associated neurological disorders (HAND). Due to continued growth in the HIV population, particularly amongst the aging cohort, the neurobiological mechanisms of HAND are increasingly relevant. Similar to other viral proteins (e. Read More

Neurochem Int 2020 12 14;141:104880. Epub 2020 Oct 14.

Department of Neuroscience, Center for Neurovirology, Lewis Katz School of Medicine at Temple University, 3500, N. Broad Street, Philadelphia, PA, USA. Electronic address:

The dysregulation of lipid homeostasis is emerging as a hallmark of many CNS diseases. As aberrant protein regulation is suggested to be a shared pathological feature amongst many neurodegenerative conditions, such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), disruptions in neuronal lipid processing may contribute to disease progression in the CNS. Specifically, given the endoplasmic reticulum (ER) dual role in lipid homeostasis as well as protein quality control (PQC) via unfolded protein response (UPR), lipid dysregulation in the CNS may converge on ER functioning and constitute a crucial mechanism underlying aberrant protein aggregation. Read More

AIDS 2021 01;35(1):63-72

Southern Alberta Clinic, Calgary.

Objective: To examine whether persons with asymptomatic neurocognitive impairment (ANI) were more likely to show progression to mild neurocognitive disorder or HIV-associated dementia than those who were neuropsychologically normal (NP-N).

Design: Longitudinal observational cohort study.

Methods: Study sample included 720 HIV-1 seropositive persons (317 with ANI and 403 NP-N) receiving care in Toronto, Canada [83% were on antiretroviral treatment; 71% had undetectable (<50 copies/ml) plasma HIVRNA]. Read More

HIV Med 2021 03 4;22(3):212-217. Epub 2020 Oct 4.

Infectious Diseases department, Beatriz Ângelo Hospital, Loures, Portugal.

Objectives: We aimed to characterize neurocognitive impairment (NI) in an HIV-2 population using an observational cross-sectional study in four Portuguese hospitals.

Methods: Adult HIV-2-infected patients were included. Montreal Cognitive Assessment Test (MoCA) and International HIV Dementia Scale (IHDS) scales were applied for screening of NI. Read More

Glia 2021 02 10;69(2):255-280. Epub 2020 Sep 10.

Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec-Université Laval, Pavillon CHUL, Québec, Quebec, Canada.

Human immunodeficiency virus type-1 (HIV-1) causes a spectrum of neurological impairments, termed HIV-associated neurocognitive disorder (HAND), following the infiltration of infected cells into the brain. Even though the implementation of antiretroviral therapy reduced the systemic viral load, the prevalence of HAND remains unchanged and infected patients develop persisting neurological disturbances affecting their quality of life. As a result, HAND have gained importance in basic and clinical researches, warranting the need of developing new adjunctive treatments. Read More

J Neurovirol 2020 12 3;26(6):809-823. Epub 2020 Sep 3.

Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh, Pittsburgh, PA, 15260, USA.

The virology of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the human immune response to the virus are under vigorous investigation. There are now several reports describing neurological symptoms in individuals who develop coronavirus disease 2019 (COVID-19), the syndrome associated with SARS-CoV-2 infection. The prevalence, incidence, and clinical course of these symptoms will become clearer in the coming months and years through epidemiological studies. Read More

J Neuroimmune Pharmacol 2020 12 2;15(4):584-627. Epub 2020 Sep 2.

Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, 1217 East Marshall Street, Richmond, VA, 23298-0613, USA.

With the current national opioid crisis, it is critical to examine the mechanisms underlying pathophysiologic interactions between human immunodeficiency virus (HIV) and opioids in the central nervous system (CNS). Recent advances in experimental models, methodology, and our understanding of disease processes at the molecular and cellular levels reveal opioid-HIV interactions with increasing clarity. However, despite the substantial new insight, the unique impact of opioids on the severity, progression, and prognosis of neuroHIV and HIV-associated neurocognitive disorders (HAND) are not fully understood. Read More

J Neuroinflammation 2020 Jul 29;17(1):226. Epub 2020 Jul 29.

Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, 92521, USA.

Background: HIV-1 infection remains a major public health concern despite effective combination antiretroviral therapy (cART). The virus enters the central nervous system (CNS) early in infection and continues to cause HIV-associated neurocognitive disorders (HAND). The pathogenic mechanisms of HIV-associated brain injury remain incompletely understood. Read More

Brain Behav Immun 2020 10 24;89:480-490. Epub 2020 Jul 24.

Laboratory of Immunophysiology, Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address:

The incidence of infectious diseases affecting the central nervous system (CNS) has been increasing over the last several years. Among the reasons for the expansion of these diseases and the appearance of new neuropathogens are globalization, global warming, and the increased proximity between humans and wild animals due to human activities such as deforestation. Neurotropism affecting normal brain function is shared by organisms such as viruses, bacteria, fungi, and parasites. Read More

AIDS 2020 09;34(11):1609-1614

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié Salpêtrière, Laboratoire de Virologie.

Objectives: To examine viral diversity and resistance mutations in different brain areas in cases of HIV-encephalopathy.

Design: Twelve postmortem brain areas from three cases of possible or certain HIV-encephalopathy were analyzed.

Methods: After amplification of the reverse transcriptase and the V3 loop region of the gp120 protein, ultradeep sequencing was performed with Illumina technology. Read More

AIDS 2020 11;34(13):1883-1889

Institute for Clinical Pharmacy and Pharmacotherapy, University Hospital Düsseldorf, Germany.

Objective: For the treatment of HIV-1-related brain disease and for the prevention of the brain becoming a viral reservoir, it is important that antiretroviral agents reach sufficient concentrations in the CNS. To date, human brain pharmacokinetic data are solely derived from lumbar cerebrospinal fluid (CSF) and mostly originate from single samples.

Design: We determined concentrations of antiretroviral drugs in serial samples of ventricular CSF and compared these to the concentrations in serum and lumbar CSF of these patients. Read More

Cell Mol Life Sci 2020 Dec 23;77(24):5079-5099. Epub 2020 Jun 23.

Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th St, Philadelphia, PA, 19102, USA.

Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription (Tat) is a potent mediator involved in the development of HIV-1-associated neurocognitive disorders (HAND). Tat is expressed even in the presence of antiretroviral therapy (ART) and is able to enter the central nervous system (CNS) through a variety of ways, where Tat can interact with microglia, astrocytes, brain microvascular endothelial cells, and neurons. The presence of low concentrations of extracellular Tat alone has been shown to lead to dysregulated gene expression, chronic cell activation, inflammation, neurotoxicity, and structural damage in the brain. Read More

J Neuroimmune Pharmacol 2020 12 12;15(4):715-728. Epub 2020 Jun 12.

Department of Psychology, University of South Carolina, Columbia, SC, USA.

The fronto-striatal circuitry, involving the nucleus accumbens, ventral tegmental area, and prefrontal cortex, mediates goal-directed behavior and is targeted by both drugs of abuse and HIV-1 infection. Acutely, both drugs and HIV-1 provoke increased dopamine activity within the circuit. However, chronic exposure to drugs or HIV-1 leads to dysregulation of the dopamine system as a result of fronto-striatal adaptations to oppose the effects of repeated instances of transiently increased dopamine. Read More