Search Our Scientific Publications & Authors

AIDS Rev 2019 ;21(2):76-83

Department of Neurology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA.

With the introduction of combinatory antiretroviral therapy, patients infected with human immunodeficiency virus type 1 (HIV-1) can live much longer than before. However, the identification of HIV-associated neurocognitive disorder (HAND), especially HIV-associated dementia in 15-20% of patients infected with HIV-1, indicates additional complexity. These disorders turn out to be subtype dependent. Read More

Neurotox Res 2019 Oct 8;36(3):563-582. Epub 2019 Jul 8.

National Toxicology Program Laboratory, National Institute of Environmental Health Sciences (NIEHS), P.O. Box 12233, MD E1-07, Research Triangle Park, NC, 27709, USA.

Animal models have been used to study cellular processes related to human immunodeficiency virus-1 (HIV-1)-associated neurocognitive disorders (HAND). The HIV-1 transgenic (Tg) rat expresses HIV viral genes except the gag-pol replication genes and exhibits neuropathological features similar to HIV patients receiving combined antiretroviral therapy (cART). Using this rat, alterations in dopaminergic function have been demonstrated; however, the data for neuroinflammation and glial reactivity is conflicting. Read More

Exp Mol Pathol 2019 06 26;108:64-72. Epub 2019 Mar 26.

Department of Neurology, University of Maryland, Baltimore, MD 21201, United States of America; VA Medical Center, Baltimore, MD 21201, United States of America. Electronic address:

HIV associated neurocognitive disorders (HAND) is a unique form of neurological impairment that stems from HIV. This disease and its characteristics can be accredited to incorporation of DNA and mRNA of HIV-1 into the CNS. A proper understanding of the intricacies of HAND and the underlying mechanisms associated with corresponding immune reactions are vital for the potential development of a reliable treatment for HAND. Read More

J Acquir Immune Defic Syndr 2019 06;81(2):216-223

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Background: Combination antiretroviral therapy (ART) improves HIV-associated neurocognitive disorder (HAND) stage in the United States where subtype B predominates, but the effect of ART and subtype on HAND stage in individuals in Uganda with subtypes D and A is largely unknown.

Setting: A community-based cohort of participants residing in Rakai, Uganda.

Methods: Three hundred ninety-nine initially ART-naive HIV-seropositive (HIV+) individuals were followed up over 2 years. Read More

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

BMC Infect Dis 2019 Feb 13;19(1):156. Epub 2019 Feb 13.

Department of Medicine, Queen Elizabeth Hospital, Hong Kong, SAR, People's Republic of China.

Background: HIV-associated neurocognitive disorder (HAND) remains prevalent in the era of combination antiretroviral therapy (cART). The prevalence of HAND in Hong Kong is not known.

Methods: Between 2013 and 2015, 98 treatment-naïve HIV-1-infected individuals were referred to and screened by the AIDS Clinical Service, Queen Elizabeth Hospital with (1) the International HIV Dementia Scale (IHDS), a screening tool that targets moderate to severe HAND, (2) the Montreal Cognitive Assessment (MoCA), a frequently used cognitive screening test and (3) the Patient Health Questionnare-9 (PHQ-9), a 9-item questionnaire that evaluates depression symptoms. Read More

Int J STD AIDS 2019 05 5;30(6):617-619. Epub 2019 Feb 5.

3 Pomeranian Hospitals, Gdansk, Poland.

We present the case of a 52-year-old man with human immunodeficiency virus (HIV) encephalitis resulting from cerebrospinal fluid (CSF) viral escape, to illustrate therapeutic challenges in patients with emergent CSF genotypic HIV drug resistance. This case report highlights the usefulness of CSF HIV-resistance testing to guide antiretroviral therapy and treatment optimizing decisions. Read More

AIDS 2019 03;33(3):593-594

CHU de Toulouse, Service des Maladies Infectieuses et Tropicales.

PLoS One 2019 17;14(1):e0203566. Epub 2019 Jan 17.

Department of Immunology and Microbiology and Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, United States of America.

Internal RNA modifications have been known for decades, however their roles in mRNA regulation have only recently started to be elucidated. Here we investigated the most abundant mRNA modification, N6-methyladenosine (m6A) in transcripts from the hippocampus of HIV transgenic (Tg) rats. The distribution of m6A peaks within HIV transcripts in HIV Tg rats largely corresponded to the ones observed for HIV transcripts in cell lines and T cells. Read More

Neurol Neuroimmunol Neuroinflamm 2019 01 7;6(1):e512. Epub 2018 Nov 7.

Department of Infectious Diseases (M.G., A.Y., L.-M.A., L.H.), Institute of Biomedicine, the Sahlgrenska Academy at University of Gothenburg, Sweden; Department of Molecular Neuroscience (A.H., E.V., H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (A.H., E.V., H.Z.), London, United Kingdom; Department of Neurology and Center for Neuroepidemiology and Clinical Neurological Research (S.S.), Yale University, New Haven, CT; Division of Biological Chemistry (D.F.), Biocenter, Medical University of Innsbruck, Austria; Department of Neurology (R.W.P.), University of California San Francisco; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.

Objective: To explore changes in CSF sTREM2 concentrations in the evolving course of HIV-1 infection.

Methods: In this retrospective cross-sectional study, we measured concentrations of the macrophage/microglial activation marker sTREM2 in CSF samples from 121 HIV-1-infected adults and 11 HIV-negative controls and examined their correlations with other CSF and blood biomarkers of infection, inflammation, and neuronal injury.

Results: CSF sTREM2 increased with systemic and CNS HIV-1 disease severity, with the highest levels found in patients with HIV-associated dementia (HAD). Read More

Sci Rep 2018 11 2;8(1):16300. Epub 2018 Nov 2.

Department of Neuroscience, Center for Neurovirology, Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, 3500N. Broad Street, Philadelphia, PA, 19140, USA.

HIV-1 Tat protein is released from HIV-1-infected cells and can enter non-permissive cells including neurons. Tat disrupts neuronal homeostasis and may contribute to the neuropathogenesis in people living with HIV (PLWH). The use of cocaine by PLWH exacerbates neuronal dysfunction. 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

Viral Immunol 2019 Jan/Feb;32(1):7-14. Epub 2018 Sep 27.

1 Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute , La Jolla, California.

Infection with Human Immunodeficiency Virus (HIV)-1 continues to cause HIV-associated neurocognitive disorders despite combined antiretroviral therapy. Interferons (IFNs) are important for any antiviral immune response, but the lasting production of IFNα causes exhaustive activation leading eventually to progression to AIDS. Expression of IFNα in the HIV-exposed central nervous system has been linked to cognitive impairment and inflammatory neuropathology. Read More

AIDS 2018 11;32(18):2707-2718

Division of Liaison Psychiatry, Department of Psychiatry and Mental Health.

Objective: To describe the structural brain changes, neurocognitive and mental health associations in adolescents perinatally infected with HIV-1 infection.

Design: Cross-sectional.

Methods: Two hundred and four adolescents with perinatally acquired HIV and 44 uninfected frequency-matched controls aged 9-11 years were enrolled within the Cape Town Adolescent Antiretroviral Cohort. Read More

J Neuroimmune Pharmacol 2018 12 13;13(4):467-478. Epub 2018 Sep 13.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China.

Nicotine, one of the key active ingredients in tobacco smoke, exerts its effects via binding to nicotinic acetylcholine receptors (nAChRs). Although both negative and positive pharmacological effects of nicotine have been shown in numerous animals and human studies, its interaction with human immunodeficiency virus-1 (HIV-1) have not been fully elucidated. Even though combined anti-retroviral therapy (cART) limits the progression of HIV-1 to acquired immune deficiency syndrome (AIDS), HIV-associated neurocognitive disorders (HAND) remain prevalent. Read More

J Neurovirol 2018 12 7;24(6):786-796. Epub 2018 Sep 7.

University of California, San Diego, San Diego, CA, USA.

Human immunodeficiency virus (HIV) genetic compartmentalization is defined as genetic differences in HIV in different tissue compartments or subcompartments that characterize viral quasispecies. This descriptive, longitudinal study assessed the dynamics of inflammation, humoral immune response, blood-brain barrier, blood-cerebrospinal fluid (CSF) barrier, as well as neuronal injury biomarkers in serially obtained CSF and serum samples from an antiretroviral (ARV) therapy-naïve patient with HIV-1 subtype C with CSF HIV genetic compartmentalization that resolved spontaneously without ARV treatment. The first CSF sample showed an increase in white blood cell (WBC) count (382 cells/mm) and a marked increase in the levels of inflammatory cytokines and chemokines, including tumor necrosis factor (TNF)α, interleukin (IL)-10, IP-10, and regulated on activation, normal T cell expressed and secreted (RANTES), which raise the suspicion of dual infection. Read More

J Neurovirol 2018 12 30;24(6):712-719. Epub 2018 Aug 30.

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

Plasma HIV RNA level has been shown to correlate with HIV disease progression, morbidity, and mortality. We examined the association between levels of plasma HIV RNA and cognitive function among patients in Nigeria. A total of 179 HIV-1-infected participants with available plasma HIV RNA results and followed longitudinally for up to 2 years were included in this study. Read More

J Neuroimmune Pharmacol 2018 09 9;13(3):345-354. Epub 2018 Jul 9.

Department of Microbiology and Medical Zoology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.

HIV-associated neurocognitive disorders (HAND) are prevalent despite combined antiretroviral therapy, affecting nearly half of HIV-infected patients worldwide. During HIV infection of macrophages secretion of the lysosomal protein, cathepsin B, is increased. Secreted cathepsin B has been shown to induce neurotoxicity. Read More

Cell Cycle 2018 21;17(13):1614-1623. Epub 2018 Aug 21.

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

The human immunodeficiency virus-1 (HIV-1) regulatory protein Tat plays an important role during HIV-1-associated neurocognitive disorders (HAND) by inducing neuronal autophagy. In this study, we used immunohistochemistry, immunofluorescence, western blot, qRT-PCR, and RNA interference to elucidate the involvement of Bcl-2-associated athanogene 3 (BAG3) in the pathogenesis of HIV-1 Tat-induced autophagy during HAND. We found that BAG3 expression is elevated in astrocytes in frontal cortex of macaques infected with simian immunodeficiency virus-human immunodeficiency chimeric virus (SHIV). 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

J Neurovirol 2018 04 11;24(2):246-253. Epub 2018 Apr 11.

Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.

Cognitive impairment in HIV-1 infection is associated with the induction of chronic proinflammatory responses in the brains of infected individuals. The risk of HIV-related cognitive impairment is increased by cigarette smoking, which induces brain inflammation in rodent models. To better understand the role of smoking and the associated immune response on behavioral and motor function in HIV infection, wild-type F344 and HIV-1 transgenic (HIV1Tg) rats were exposed to either smoke from nicotine-containing (regular) cigarettes, smoke from nicotine-free cigarettes, or to nicotine alone. 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

J Neurovirol 2018 04 26;24(2):137-140. Epub 2018 Mar 26.

Division of AIDS Research, National Institute of Mental Health, Rm 9G20, 5601 Fishers Lane, Bethesda, MD, 20892, USA.

Curr HIV/AIDS Rep 2018 02;15(1):72-83

The Aaron Diamond AIDS Research Center, 455 First Avenue, 7th Floor, New York, NY, 10016, USA.

Purpose Of Review: The HIV-1 envelope gene (env) has been an intense focus of investigation in the search for genetic determinants of viral entry and persistence in the central nervous system (CNS).

Recent Findings: Molecular signatures of CNS-derived HIV-1 env reflect the immune characteristics and cellular constraints of the CNS compartment. Although more readily found in those with advanced HIV-1 and HIV-associated neurocognitive disorders (HAND), molecular signatures distinguishing CNS-derived quasispecies can be identified early in HIV-1 infection, in the presence or absence of combination antiretroviral therapy (cART), and are dynamic. Read More

Curr HIV/AIDS Rep 2018 02;15(1):84-91

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

Purpose Of Review: Neurocognitive disorders are not uncommon in HIV-positive patients but their pathogenesis is multifactorial and incompletely understood. After excluding contributing comorbidities, several factors may impair neurocognition including severe immune suppression, incomplete antiviral efficacy, drugs' persistent immune activation, vascular abnormalities, and drugs' neurotoxicity. The effectiveness of targeted antiretroviral strategies on these risk factors is unknown. 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

J Neurovirol 2018 04 18;24(2):192-203. Epub 2017 Dec 18.

Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Most studies of HIV latency focus on the peripheral population of resting memory T cells, but the brain also contains a distinct reservoir of HIV-infected cells in microglia, perivascular macrophages, and astrocytes. Studying HIV in the brain has been challenging, since live cells are difficult to recover from autopsy samples and primate models of SIV infection utilize viruses that are more myeloid-tropic than HIV due to the expression of Vpx. Development of a realistic small animal model would greatly advance studies of this important reservoir and permit definitive studies of HIV latency. Read More

J Neurovirol 2018 04 18;24(2):146-155. Epub 2017 Dec 18.

Department of Neurology, University of Pennsylvania, Philadelphia, PA, 19104-6140, USA.

HIV-infected patients treated with antiretroviral medicines (ART) still face neurological challenges. HIV-associated neurocognitive disturbances (HAND) can occur, and latent viral DNA persisting in the central nervous system (CNS) prevents eradication of HIV. This communication focuses on how to develop experimental models of HAND and CNS HIV latency that best imitate the CNS pathophysiology in diseased humans, which we take to be "the real thing. 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

J Neurovirol 2018 04 15;24(2):168-179. Epub 2017 Nov 15.

Graduate School of Biomedical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA.

HIV-1 Tat is known to be neurotoxic and important for HIV/neuroAIDS pathogenesis. However, the overwhelming majority of the studies involved use of recombinant Tat protein. To understand the contributions of Tat protein to HIV/neuroAIDS and the underlying molecular mechanisms of HIV-1 Tat neurotoxicity in the context of a whole organism and independently of HIV-1 infection, a doxycycline-inducible astrocyte-specific HIV-1 Tat transgenic mouse (iTat) was created. Read More

J Neurovirol 2018 02 31;24(1):113-118. Epub 2017 Oct 31.

Department of Immunology and Microbiology, Rush University Medical Center, Cohn Research Building, Rm.414, 1735 W. Harrison Street, Chicago, IL, 60612, USA.

We assessed firing and voltage-gated Ca influx in medial prefrontal cortex (mPFC) pyramidal neurons from older (12 months old) HIV-1 transgenic (Tg) rats. We found that neurons from older Tg rats showed increased firing compared to non-Tg rats, but Ca spikes were unchanged. However, stronger excitatory stimulation was needed to evoke Ca spikes, which was associated with reduced mPFC Ca1. Read More

J Neurovirol 2018 04 26;24(2):156-167. Epub 2017 Oct 26.

Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.

HIV-1 infection causes injury to the central nervous system (CNS) and is often associated with neurocognitive disorders. One model for brain damage seen in AIDS patients is the transgenic (tg) mouse expressing a soluble envelope protein gp120 of HIV-1 LAV in the brain in astrocytes under the control of the promoter of glial fibrillary acidic protein. These GFAP-gp120tg mice manifest several key neuropathological features observed in AIDS brains, such as decreased synaptic and dendritic density, increased numbers of activated microglia, and pronounced astrocytosis. Read More

J Neurovirol 2018 02 23;24(1):16-27. Epub 2017 Oct 23.

Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Paroxetine and fluconazole have neuroprotective effects in an in vitro model of HIV protein-mediated neuronal injury. This study evaluated the safety, tolerability, and efficacy of both paroxetine and fluconazole for the treatment of HIV-associated neurocognitive disorder (HAND). A 24-week randomized double-blind, placebo-controlled 2 × 2 factorial design study was used. Read More

J Neurovirol 2018 02 23;24(1):41-51. Epub 2017 Oct 23.

Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.

Despite the availability of effective antiretroviral therapies, cognitive impairment (CI) remains prevalent in HIV-infected (HIV+) individuals. Evidence from primarily cross-sectional studies, in predominantly male samples, implicates monocyte- and macrophage-driven inflammatory processes linked to HIV-associated CI. Thus, peripheral systemic inflammatory markers may be clinically useful biomarkers in tracking HIV-associated CI. Read More

J Neurovirol 2018 02 23;24(1):1-15. Epub 2017 Oct 23.

The University of California, San Francisco, CA, USA.

HIV-1 Nef is a flexible, multifunctional protein with several cellular targets that is required for pathogenicity of the virus. This protein maintains a high degree of genetic variation among intra- and inter-host isolates. HIV Nef is relevant to HIV-associated neurological diseases (HAND) in patients treated with combined antiretroviral therapy because of the protein's role in promoting survival and migration of infected brain macrophages. 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 Neurovirol 2018 04 11;24(2):180-184. Epub 2017 Sep 11.

Psychology Department, Arizona State University, Tempe, AZ, USA.

HIV-associated neurocognitive disorders (HAND) remain highly prevalent despite combined antiretroviral therapy (cART). Although the most common forms of HAND are mild and identified through neuropsychological testing, there is evidence that with aging these mild forms become more prevalent and may advance to the most severe form of HAND, HIV-associated dementia. Therefore, novel therapies must be developed that can be used adjunctively with cART to prevent deterioration or restore normal cognitive function. 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

J Neurovirol 2018 04 22;24(2):185-191. Epub 2017 Aug 22.

Division of Infectious Diseases, Center for AIDS Research, University of North Carolina (UNC), School of Medicine, Chapel Hill, NC, USA.

While the human immunodeficiency virus (HIV) epidemic was initially characterized by a high prevalence of severe and widespread neurological pathologies, the development of better treatments to suppress viremia over years and even decades has mitigated many of the severe neurological pathologies previously observed. Despite effective treatment, mild neurocognitive impairment and premature cognitive aging are observed in HIV-infected individuals, suggesting a changing but ongoing role of HIV infection in the central nervous system (CNS). Although current therapies are effective in suppressing viremia, they are not curative and patients must remain on life-long treatment or risk recrudescence of virus. 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

J Neurovirol 2018 04 27;24(2):141-145. Epub 2017 Jul 27.

Department of Neurology, Johns Hopkins Neurology School of Medicine, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, 301 Building, Suite 2100, Baltimore, MD, 21224, USA.

HIV-associated neurocognitive disorder (HAND) remains a common cause of cognitive impairment and persists in 15-55% of HIV+ individuals in the combination antiretroviral therapy (CART) era. CART is now the primary treatment for HAND, but it is effective in only a subset of patients. In the pre-CART era, HIV-associated dementia was the most common form of HAND. Read More