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Gene 2019 May 27;698:41-49. Epub 2019 Feb 27.

Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India.

Matrix metalloproteinases (MMPs) play a key role in several diseases such as rheumatoid arthritis, HIV-associated neurological diseases (HAND), multiple sclerosis, osteoporosis, stroke, Alzheimer's disease, certain viral infections of the central nervous system, cancer, and hepatitis C virus. MMPs have been explained with regards to extracellular matrix remodeling, which occurs throughout life and ranges from tissue morphogenesis to wound healing in various processes. MMP are inhibited by endogenous tissue inhibitors of metalloproteinases (TIMPs). Read More

J Neuroinflammation 2018 Oct 10;15(1):285. Epub 2018 Oct 10.

Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, 1217 E. Marshall St, Richmond, VA, 23298-0709, USA.

Background: The collective cognitive and motor deficits known as HIV-associated neurocognitive disorders (HAND) remain high even among HIV+ individuals whose antiretroviral therapy is optimized. HAND is worsened in the context of opiate abuse. The mechanism of exacerbation remains unclear but likely involves chronic immune activation of glial cells resulting from persistent, low-level exposure to the virus and viral proteins. Read More

Front Neurol 2018 21;9:791. Epub 2018 Sep 21.

Department of Diagnostics and Public Health, University of Verona, Verona, Italy.

AIDS dementia complex (ADC) and HIV-associated neurocognitive disorders (HAND) are complications of HIV-1 infection. Viral infections are risk factors for the development of neurodegenerative disorders. Aging is associated with low-grade inflammation in the brain, i. Read More

Biomol Concepts 2018 May 8;9(1):33-42. Epub 2018 May 8.

Center for Advanced Research (CFAR)-Stem Cell/Cell Culture Unit, King George's Medical University (KGMU), Lucknow, 226003, India.

Among Human immunodeficiency virus (HIV) infected individuals, around two-thirds of patients present with neuroAIDS, where HIV-associated neurocognitive disorders (HAND), and HIV-associated dementia (HAD) are the most prevailing neurological complications. The neuropathology of neuroAIDS can be characterized by the presence of HIV infected macrophages and microglia in the brain, with the formation of multinucleated giant cells. Global predominant subtypes of HIV-1 clade B and C infections influence the differential effect of immune and neuronal dysfunctions, leading to clade-specific clinical variation in neuroAIDS patient cohorts. Read More

Behav Brain Res 2018 09 27;349:73-79. Epub 2018 Apr 27.

Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.

Mild neurocognitive impairments are common in people with human immunodeficiency virus (HIV) infection. HIV-encoded proteins, such as trans-activator of transcription (TAT), contribute to neuropathology and cognitive function in medicated subjects. The combination of TAT and comorbid methamphetamine use may further impair neurocognitive function in HIV-positive individuals by affecting dopaminergic systems in the brain. Read More

J Neuroinflammation 2018 Apr 27;15(1):126. Epub 2018 Apr 27.

Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2117 Pitt Public Health, 130 DeSoto Street, Pittsburgh, PA, 15261, USA.

Background: Human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorder (HAND) is a common outcome of a majority of HIV-1-infected subjects and is associated with synaptodendritic damage. Neurogranin (Ng), a postsynaptic protein, and calmodulin (CaM) are two important players of synaptic integrity/functions. The biological role of Ng in the context of HAND is unknown. Read More

Handb Clin Neurol 2018 ;152:99-116

Department of Infectious Diseases, Red Cross War Memorial Children's Hospital, Cape Town, South Africa.

The human immunodeficiency virus-1 (HIV-1) enters the central nervous system compartment within the first few weeks of systemic HIV infection and may cause a spectrum of neurologic complications. Without combination antiretroviral therapy (cART), 50-90% of all HIV-infected infants and children develop some form of neuroAIDS. Of the estimated 2. Read More

Handb Clin Neurol 2018 ;152:21-40

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States. Electronic address:

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) remain a common end-organ manifestation of viral infection. Subclinical and mild symptoms lead to neurocognitive and behavioral abnormalities. These are associated, in part, with viral penetrance and persistence in the central nervous system. Read More

Glia 2018 04 13;66(4):889-902. Epub 2018 Jan 13.

Department of Neuroscience, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.

Cholesterol synthesis and clearance by astrocytes are tightly regulated to maintain constant levels within the brain. In this context, liver X receptors (LXRs) are the master regulators of cholesterol homeostasis in the central nervous system (CNS). Increasing levels of cholesterol in astrocytes trigger LXR activation leading to the transcription of target genes involved in cholesterol trafficking and efflux, including apolipoprotein E, cytochrome P450 enzymes, sterol regulatory binding protein, and several ATP-binding cassette transporter proteins. Read More

Int J STD AIDS 2018 06 17;29(7):726-728. Epub 2017 Dec 17.

1 Prayas, Pune, India.

Cerebrospinal fluid (CSF) escape phenomenon is widely studied and documented in HIV-1. However, hardly anything is known about progressive neurologic disease in otherwise well-controlled HIV-2 infection. We present a case of neurosymptomatic CSF escape in HIV-2 infection from India. Read More

Gene 2018 Feb 6;643:133-143. Epub 2017 Dec 6.

Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address:

The PURA gene encodes Pur-alpha, a 322 amino acid protein with repeated nucleic acid binding domains that are highly conserved from bacteria through humans. PUR genes with a single copy of this domain have been detected so far in spirochetes and bacteroides. Lower eukaryotes possess one copy of the PUR gene, whereas chordates possess 1 to 4 PUR family members. Read More

J Infect Dis 2018 01;217(4):521-528

Department of Pathology and Laboratory Medicine, University of Vermont Larner College of Medicine, Colchester.

Despite achieving human immunodeficiency virus type 1 (HIV-1) RNA suppression below levels of detection and, for most, improved CD4+ T-cell counts, those aging with HIV experience excess low-level inflammation, hypercoagulability, and immune dysfunction (chronic inflammation), compared with demographically and behaviorally similar uninfected individuals. A host of biomarkers that are linked to chronic inflammation are also associated with HIV-associated non-AIDS-defining events, including cardiovascular disease, many forms of cancer, liver disease, renal disease, neurocognitive decline, and osteoporosis. Furthermore, chronic HIV infection may interact with long-term treatment toxicity and weight gain after ART initiation. Read More

J Neurovirol 2017 Dec 16;23(6):935-940. Epub 2017 Nov 16.

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

Despite the success of combination antiretroviral therapy (cART), there is increased prevalence of HIV-associated neurocognitive disorders (HAND) in HIV-1-infected individuals on cART, which poses a major health care challenge. Adding further complexity to this long-term antiretroviral use is the comorbidity with drugs of abuse such as morphine, cocaine, and methamphetamine, which can in turn, exacerbate neurologic and cognitive deficits associated with HAND. Furthermore, HIV proteins, such as the transactivator of transcription (Tat) and the envelope protein (gp120), as well as antiretrovirals themselves can also contribute to the progression of neurodegeneration underlying HAND. Read More

Pharmacol Ther 2018 03 5;183:78-89. Epub 2017 Oct 5.

Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, Lexington, KY, USA; Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA.

HIV-associated neurocognitive disorder (HAND) remains highly prevalent in HIV infected individuals and represents a special group of neuropathological disorders, which are associated with HIV-1 viral proteins, such as transactivator of transcription (Tat) protein. Cocaine abuse increases the incidence of HAND and exacerbates its severity by enhancing viral replication. Perturbation of dopaminergic transmission has been implicated as a risk factor of HAND. Read More

J Neuroinflammation 2017 Sep 8;14(1):183. Epub 2017 Sep 8.

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON, M5S 3M2, Canada.

Background: Despite the use of combination antiretroviral therapy for the treatment of HIV-1 infection, cognitive impairments remain prevalent due to persistent viral replication and associated brain inflammation. Primary cellular targets of HIV-1 in the brain are macrophages, microglia, and to a certain extent astrocytes which in response to infection release inflammatory markers, viral proteins [i.e. Read More

PLoS One 2017 8;12(8):e0181642. Epub 2017 Aug 8.

Institute of Neuroimmune Pharmacology/Center for Personalized Nanomedicine, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, United States of America.

The neurological complications of AIDS (neuroAIDS) during the infection of human immunodeficiency virus (HIV) are symptomized by non-specific, multifaceted neurological conditions and therefore, defining a specific diagnosis/treatment mechanism(s) for this neuro-complexity at the molecular level remains elusive. Using an in silico based integrated gene network analysis we discovered that HIV infection shares convergent gene networks with each of twelve neurological disorders selected in this study. Importantly, a common gene network was identified among HIV infection, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and age macular degeneration. Read More

J Neurovirol 2017 08 31;23(4):603-614. Epub 2017 Jul 31.

Center for Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.

Drug abuse (e.g., methamphetamine-Meth or cocaine-Coc) is one of the major risk factors for becoming infected with HIV-1, and studies show that in combination, drug abuse and HIV-1 lead to significantly greater damage to CNS. Read More

Pediatr Infect Dis J 2017 Nov;36(11):e264-e267

From the *Children's Infectious Diseases Clinical Research Unit (KID-CRU), Stellenbosch University, and †Department of Paediatrics and Child Health, Tygerberg Children's Hospital, Cape Town, South Africa; ‡Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Soweto, South Africa; and §Division of Medical Virology, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa.

We describe 4 Children with HIV Early Antiretroviral Therapy trial participants with late-onset HIV encephalopathy despite long-standing viral suppression in blood and undetectable HIV DNA and RNA polymerase chain reaction in cerebrospinal fluid. Extensive investigations revealed no alternative etiology. Reassuringly, all 4 experienced slow spontaneous recovery despite no change in antiretroviral therapy. Read More

J Neurovirol 2017 10 17;23(5):679-685. Epub 2017 Jul 17.

Infectious Diseases Service, Hospital Clínic-IDIBAPS, Villarroel, 170, 08036, Barcelona, Spain.

Primary HIV-1 infection is a relevant period for its virological and epidemiological consequences. Most patients present a symptomatic disease that can be potentially serious, but neurological involvement during primary HIV-1 infection has been poorly studied. The aim of this study was to describe the characteristics and outcomes of primary HIV-1 infection patients presenting neurological symptoms and to compare them with primary HIV-1 infection patients without neurological involvement. Read More

N Engl J Med 2017 06;376(26):2580-2589

From the Departments of Neurology (S.S.M.), Radiology (R.G.G.), Medicine (R.T.G.), and Pathology (S.K.), Massachusetts General Hospital, and the Departments of Neurology (S.S.M.), Radiology (R.G.G.), Medicine (R.T.G.), and Pathology (S.K.), Harvard Medical School - both in Boston.

Aging Cell 2017 10 13;16(5):956-965. Epub 2017 Jun 13.

Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL, 60612, USA.

Emerging evidence suggests that cell senescence plays an important role in aging-associated diseases including neurodegenerative diseases. HIV leads to a spectrum of neurologic diseases collectively termed HIV-associated neurocognitive disorders (HAND). Drug abuse, particularly methamphetamine (meth), is a frequently abused psychostimulant among HIV+ individuals and its abuse exacerbates HAND. Read More

J Neurol 2017 Aug 31;264(8):1715-1727. Epub 2017 May 31.

HIV-Schwerpunktpraxis, 30890, Barsinghausen, Germany.

The modern antiretroviral treatment of human immunodeficiency virus (HIV-1) infection has considerably lowered the incidence of opportunistic infections. With the exception of the most severe dementia manifestations, the incidence and prevalence of HIV-associated neurocognitive disorders (HAND) have not decreased, and HAND continues to be relevant in daily clinical practice. Now, HAND occurs in earlier stages of HIV infection, and the clinical course differs from that before the widespread use of combination antiretroviral treatment (cART). Read More

Eur Rev Med Pharmacol Sci 2017 05;21(9):2290-2301

Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.

Objective: The purpose of the present multidisciplinary review is to give an updated insight into the most recent findings regarding the pathophysiology, diagnosis and therapeutics of HIV-associated neurocognitive disorder (HAND).

Materials And Methods: We performed a comprehensive search, through electronic databases (Pubmed - MEDLINE) and search engines (Google Scholar), of peer-reviewed publications (articles and reviews) and conferences proceedings on HAND pathophysiology, diagnosis, and therapy, from 1999 to 2016.

Results: It seems to be increasingly clear that neurodegeneration in HIV-1 affected patients is a multi-faceted disease involving numerous factors, from chronic inflammation to central nervous system (CNS) compartmentalization of HIV. Read More

Brain Behav Immun 2017 Oct 6;65:161-172. Epub 2017 May 6.

Indiana Center for AIDS Research and Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, United States; Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address:

HIV-1-associated neurocognitive disorders (HAND) continue to be a major concern in the infected population, despite the widespread use of combined antiretroviral therapy (cART). Growing evidence suggests that an imbalance between matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of MMPs (TIMPs) contributes to the pathogenesis of HAND. In our present study, we examined protein levels and enzymatic activities of MMPs and TIMPs in both plasma and cerebrospinal fluid (CSF) samples from HIV-1 patients with or without HAND and HIV-1-negative controls. Read More

Clin Infect Dis 2017 04;64(8):1059-1065

Division of Infection and Immunity, University College London, United Kingdom.

Background: Human immunodeficiency virus type 1 (HIV-1) can replicate independently in extravascular compartments such as the central nervous system, resulting in either cerebrospinal fluid (CSF) discordance (viral load [VL] in CSF 0.5 log10 copies HIV-1 RNA greater than plasma VL) or escape (detection of HIV VL >50 copies/mL in CSF in patients with suppressed plasma VL <50 copies/mL). Both discordance and escape may be associated with neurological symptoms. Read More

J Neurovirol 2017 06 27;23(3):474-482. Epub 2017 Feb 27.

University of Maryland School of Medicine, Baltimore, MD, 21201, USA.

Mononuclear cells play key roles in the pathogenic mechanisms leading to HIV-associated neurocognitive disorders (HANDs). We examined the association between HIV DNA within peripheral blood mononuclear cell (PBMC) subsets and HAND in Nigeria. PBMCs were collected at baseline from 36 antiretroviral naive participants. Read More

Oncotarget 2017 Mar;8(11):18082-18094

Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, Department of Pathology, Basic Medicine, Medical College, Xiamen University, Xiamen, Fujian 361102, China.

The molecular mechanisms involved in human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remain poorly understood. It has been recently reported that HIV-1 Tat transactivation requires menin, suggesting that menin may be involved in HAND pathogenesis. But the role of menin is not clear. Read More

Drugs 2017 Feb;77(2):145-157

Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, c/o Ospedale Amedeo di Savoia, C.so Svizzera 164, 10159, Torino, Italy.

Combination antiretroviral treatment is associated with clear benefits in HIV-positive subjects, and is also effective in the central nervous system (CNS), meaning HIV-associated dementia is now an uncommon event. Nevertheless, a significant number of patients show symptoms of neurocognitive impairment which may negatively affect their quality of life. Although several risk factors for HIV-associated neurocognitive disorders have been identified, there is no clear recommendation for their prevention and management. Read More

Mol Cell Neurosci 2017 03 29;79:12-22. Epub 2016 Dec 29.

Department of Biochemistry and Molecular Biology, 1011 NW 15th Street, Gautier Building, Room 528, University of Miami School of Medicine, Miami, FL 33136-1019, USA. Electronic address:

HIV-infected brains are characterized by increased amyloid beta (Aβ) deposition. It is believed that the blood-brain barrier (BBB) is critical for Aβ homeostasis and contributes to Aβ accumulation in the brain. Extracellular vesicles (ECV), like exosomes, recently gained a lot of attention as potentially playing a significant role in Aβ pathology. Read More

AIDS 2017 03;31(5):623-633

aDepartment of Infectious Diseases & Microbiology, Graduate School of Public Health, University of Pittsburgh bComputer Science Department, School of Computer Science, Carnegie Mellon University cMolecular Biology Information Service, University of Pittsburgh dComputational Biology and Machine Learning Department, Carnegie Mellon University, Pittsburgh, Pennsylvania eDepartment of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois fDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland gDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, California hDepartment of Psychiatry, Rush University Medical Center, Chicago, Illinois iDepartment of Neurology, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Objective: HIV-1 viral proteins and host inflammatory factors have a direct role in neuronal toxicity in vitro; however, the contribution of these factors in vivo in HIV-1-associated neurocognitive disorder (HAND) is not fully understood. We applied novel Systems Biology approaches to identify specific cellular and viral factors and their related pathways that are associated with different stages of HAND.

Design: A cross-sectional study of individuals enrolled in the Multicenter AIDS Cohort Study including HIV-1-seronegative (N = 36) and HIV-1-seropositive individuals without neurocognitive symptoms (N = 16) or with mild neurocognitive disorder (MND) (N = 8) or HIV-associated dementia (HAD) (N = 16). Read More

AIDS 2016 11;30(17):2591-2597

aUniversity of California, San Diego, La Jolla, California, USA bINSERM UMR U966, Tours, France cVeterans Affairs San Diego Healthcare System, San Diego, California, USA.

Objective: Compared with HIV monoinfection, HIV dual infection has been associated with decreased CD4 T-cell counts and increased viral loads. The same markers are also associated with the development of HIV-associated neurocognitive disorder (HAND), which continues to be a prevalent problem in the era of combination antiretroviral therapy (ART). We sought to determine the relationship between dual infection and HAND. Read More

J Neurosci 2016 10;36(41):10683-10695

Department of Medicine, Department of Medical Microbiology and Immunology, and Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada T6G 2S2, and

HIV-1 infection of the brain causes the neurodegenerative syndrome HIV-associated neurocognitive disorders (HAND), for which there is no specific treatment. Herein, we investigated the actions of insulin using ex vivo and in vivo models of HAND. Increased neuroinflammatory gene expression was observed in brains from patients with HIV/AIDS. Read More

Appl Neuropsychol Adult 2017 Nov-Dec;24(6):512-521. Epub 2016 Aug 15.

g Department of Psychiatry and Behavioral Sciences, Quillen College of Medicine , East Tennessee State University , Johnson City , Tennessee , USA.

Given that neurocognitive impairment is a frequent complication of HIV-1 infection in Spanish-speaking adults, the limited number of studies assessing HIV-associated neurocognitive disorders (HAND) in this population raises serious clinical concern. In addition to being appropriately translated, instruments need to be modified, normed, and validated accordingly. The purpose of the current study was to examine the diagnostic utility of the HIV Dementia Scale (HDS) and International HIV Dementia Scale (IHDS) to screen for HAND in Spanish-speaking adults living with HIV infection. Read More

J Assoc Physicians India 2015 08;63(8):85-6

Cl Spl Psychiatry, Command Hospital (CC), Lucknow, Uttar Pradesh.

We present a case of dementia in a young healthy individual. On evaluation he was detected to have HIV infection with low CD4 count and a high viral load. He had no opportunistic infections or any other AIDS defining illnesses. Read More

J Gene Med 2016 Sep;18(9):250-7

Department of Clinical Sciences, National AIDS Research Institute, Pune, India.

Background: Astrocytes are susceptible to HIV-1 infection. Neurocognitive dysfunction has also been associated with the toxicity of certain antiretroviral drugs. HIV-1 induced neurological toxicity has been associated with deficiency of matrix metalloproteinases. Read More

APMIS 2016 Nov 19;124(11):966-972. Epub 2016 Aug 19.

Department of Clinical Sciences, National AIDS Research Institute, Pune, India.

The HIV-1-induced neurological toxicity has been associated with the deficiency of matrix metalloproteinases. Tat protein of HIV up regulates MMP-7 release and activation, leading to neurotoxicity. The SNP -181A>G of MMP-7 is known to have functional effects on its promoter activity. Read More

J Neurovirol 2016 10 29;22(5):699-702. Epub 2016 Jul 29.

Division of AIDS Research, National Institute of Mental Health, NIH, Bethesda, MD, USA.

Despite major advances in HIV-1 treatment, the prevalence of HIV-associated neurocognitive disorders (HAND) remains a problem, particularly as individuals on suppressive treatment continue to live longer. To facilitate discussion on emerging and future directions in HAND research, a meeting was held in Durban, South Africa in March 2015 as part of the Society of Neuroscientists of Africa (SONA) conference. The objective of the meeting was to assess the impact of HIV subtype diversity on HAND and immunological dysfunction. Read More

Virulence 2017 07 19;8(5):599-604. Epub 2016 Jul 19.

a Department of Infectious Diseases , Institute of Biomedicine, University of Gothenburg , Gothenburg , Sweden.

Background: The prevalence of neurocognitive deficits are reported to be high in HIV-1 positive patients, even with suppressive antiretroviral treatment, and it has been suggested that HIV can cause accelerated aging of the brain. In this study we measured phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) as a potential marker for premature central nervous system (CNS) aging. P-tau increases with normal aging but is not affected by HIV-associated neurocognitive disorders. Read More

J Neurovirol 2016 12 11;22(6):866-870. Epub 2016 Jul 11.

Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA.

We previously reported that mRNA expression of the unique alternatively spliced OPRM1 isoform μ-opioid receptor-1K (MOR-1K), which exhibits excitatory cellular signaling, is elevated in HIV-infected individuals with combined neurocognitive impairment (NCI) and HIV encephalitis (HIVE). It has recently been shown that the β-adrenergic receptor (β-AR) chaperones MOR-1K, normally localized intracellularly, to the cell surface. Here, we found mRNA expression of the adrenoceptor beta 2 (ADRB2) gene is also elevated in NCI-HIVE individuals, as well as that β-AR protein expression is elevated in HIV-1-infected primary human astrocytes treated with morphine, and discuss the implications for MOR-1K subcellular localization in this condition. Read More

PLoS One 2016 13;11(6):e0157160. Epub 2016 Jun 13.

Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Objective: Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients on antiretroviral therapy (ART). We examined the relationship between mild HAND and CSF neurofilament light protein (NFL), a biomarker of neuronal injury; and CSF neopterin, a biomarker of CNS immunoactivation, in virally suppressed patients on antiretroviral therapy (ART).

Design And Methods: We selected 99 subjects on suppressive ART followed longitudinally from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Read More

Sci Rep 2016 05 31;6:26876. Epub 2016 May 31.

Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 672, Rochester, NY 14642, USA.

Human Immunodeficiency Virus type-1 (HIV)-associated neurocognitive disorder is characterized by recruitment of activated/infected leukocytes into the CNS via disrupted Blood Brain Barrier (BBB) that contributes to persistent neuro-inflammation. In this report, humanized NOD/scid-IL2Rγc(null) mice were used to establish that impaired Sonic hedgehog (Shh) signaling is associated with loss of BBB function and neurological damage, and that modulating Shh signaling can rescue these detrimental effects. Plasma viral load, p24 levels and CD4(+) T cells were measured as markers of productive HIV infection. Read More

Curr HIV/AIDS Rep 2016 08;13(4):209-17

Memory and Aging Center, MC: 1207, Sandler Neurosciences Building, 675 Nelson Rising Lane, Room 192C, Department of Neurology, University of California San Francisco, San Francisco, CA, 94143-1207, USA.

The implementation of combination antiretroviral therapy (cART) has changed HIV infection into a chronic illness, conveying extensive benefits, including greater longevity and advantages for the central nervous system (CNS). However, studies increasingly confirm that the CNS gains are incomplete, with reports of persistent immune activation affecting the CNS despite suppression of plasma HIV RNA. The rate of cognitive impairment is unchanged, although severity is generally milder than in the pre-cART era. Read More

J Clin Invest 2016 06 9;126(6):2295-307. Epub 2016 May 9.

Current antiretroviral therapy (ART) is not sufficient to completely suppress disease progression in the CNS, as indicated by the rising incidence of HIV-1-associated neurocognitive disorders (HAND) among infected individuals on ART. It is not clear why some HIV-1-infected patients develop HAND, despite effective repression of viral replication in the circulation. SIV-infected nonhuman primate models are widely used to dissect the mechanisms of viral pathogenesis in the CNS. Read More

Prog Neurobiol 2017 Oct 14;157:133-157. Epub 2016 Apr 14.

Department of Cell Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX, 76107-2699, USA. Electronic address:

Recent attempts to analyze human immunodeficiency virus (HIV)-1-induced gene expression changes in astrocytes uncovered a multifunctional oncogene, astrocyte elevated gene-1 (AEG-1). Our previous studies revealed that AEG-1 regulates reactive astrocytes proliferation, migration and inflammation, hallmarks of aging and CNS injury. Moreover, the involvement of AEG-1 in neurodegenerative disorders, such as Huntington's disease and migraine, and its induction in the aged brain suggest a plausible role in regulating overall CNS homeostasis and aging. Read More

J Neurovirol 2016 10 28;22(5):584-596. Epub 2016 Mar 28.

Department of Medicine, University of Pennsylvania Perelman School of Medicine, 36th and Hamilton Walk, Philadelphia, PA, 19104, USA.

HIV-1-associated neurocognitive disorder (HAND) remains a persistent problem despite antiretroviral therapy (ART), largely a result of continued inflammation in the periphery and the brain and neurotoxin release from activated myeloid cells in the CNS. CD14+CD16+ inflammatory monocytes, expanded in HIV infection, play a central role in the pathogenesis of HAND and have parallels with monocyte-dependent inflammatory mechanisms in atherosclerosis. Statins, through their HMG-CoA reductase inhibitor activity, have pleiotropic immunomodulatory properties that contribute to their benefit in atherosclerosis beyond lipid lowering. Read More

Curr HIV Res 2016 ;14(5):417-430

Department, of Pathology and Microbiology and Immunology, F727, Albert Einstein College of Medicine, 1300 Morris Park Ave. Bronx, NY, 10461, USA.

Background: HIV-1 enters the CNS within two weeks after peripheral infection and results in chronic neuroinflammation that leads to HIV associated neurocognitive disorders (HAND) in more than 50% of infected people. HIV enters the CNS by transmigration of infected monocytes across the blood brain barrier. Intravenous drug abuse is a major risk factor for HIV-1 infection, and opioids have been shown to alter the progression and severity of HAND. Read More

Curr HIV Res 2016 ;14(5):389-399

HIV Neuropathogenesis, Genetics, and Therapeutics Branch, Division of AIDS Research, National Institute of Mental Health, Bethesda, MD-20892, USA.

Background: Over the past three decades, the clinical presentation of HIV infection of the Central Nervous System (CNS) has evolved. Prior to wide spread use of effective antiretroviral therapy (ART), more than a third of infected individuals exhibited a range of neurocognitive and motor deficits that frequently progressed to severe dementia and paralysis. However, the use of ART has significantly decreased the prevalence of severe forms of HIV-1 associated neurocognitive disorders (HAND). Read More

PLoS One 2016 17;11(3):e0151702. Epub 2016 Mar 17.

Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.

The number of HIV-1 positive individuals developing some form of HIV-associated neurocognitive disorder (HAND) is increasing. In these individuals, the integrity of the blood-brain barrier (BBB) is compromised due to an increase in exposure to pro-inflammatory mediators, viral proteins, and virus released from infected cells. It has been shown that soluble CD40L (sCD40L) is released upon platelet activation and is an important mediator of the pathogenesis of HAND but the underlying mechanisms are unclear, emphasizing the need of an effective animal model. Read More

Adv Drug Deliv Rev 2016 08 2;103:202-17. Epub 2016 Mar 2.

Center for Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.

In spite of significant advances in antiretroviral (ARV) therapy, the elimination of human immunodeficiency virus (HIV) reservoirs from the periphery and the central nervous system (CNS) remains a formidable task. The incapability of ARV to go across the blood-brain barrier (BBB) after systemic administration makes the brain one of the dominant HIV reservoirs. Thus, screening, monitoring, and elimination of HIV reservoirs from the brain remain a clinically daunting and key task. Read More