Sex Differences in the Risk of Stroke Associated With Traditional and Non-Traditional Factors in a US Cohort of People With HIV Infection.

Background And Objectives: Although stroke risk associated with HIV may be greater for women than men, little is known about whether the impact of different factors on cerebrovascular risk varies by sex in people with HIV (PWH) and contributes to stroke risk disparities in this population. The primary objective of this study was to examine whether sex modifies the effect of demographics, cardiometabolic factors, health-related behaviors, and HIV-specific variables on stroke risk in PWH from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort.

Methods: In this observational cohort study, we analyzed data from clinical encounters for PWH followed at 5 CNICS sites from approximately 2005 to 2020.

Types of Stroke Among People Living With HIV in the United States.

Background: Most studies of stroke in people living with HIV (PLWH) do not use verified stroke diagnoses, are small, and/or do not differentiate stroke types and subtypes.

Setting: CNICS, a U.S.

HIV Viremia and Risk of Stroke Among People Living with HIV Who Are Using Antiretroviral Therapy.

Background: Rates of stroke are higher in people living with HIV compared with age-matched uninfected individuals. Causes of elevated stroke risk, including the role of viremia, are poorly defined.

Methods: Between 1 January 2006 and 31 December 2014, we identified incident strokes among people living with HIV on antiretroviral therapy at five sites across the United States.

Association Between Bilirubin, Atazanavir, and Cardiovascular Disease Events Among People Living With HIV Across the United States.

Objective: Bilirubin is an antioxidant that may suppress lipid oxidation. Elevated bilirubin is associated with decreased cardiovascular events in HIV-uninfected populations. We examined these associations in people living with HIV (PLWH).

Neurosyphilis Increases Human Immunodeficiency Virus (HIV)-associated Central Nervous System Inflammation but Does Not Explain Cognitive Impairment in HIV-infected Individuals With Syphilis.

Background: Individuals infected with human immunodeficiency virus (HIV) who have previously had syphilis may have cognitive impairment. We tested the hypothesis that neurosyphilis causes cognitive impairment in HIV by amplifying HIV-related central nervous system (CNS) inflammation.

Methods: HIV-infected participants enrolled in a study of cerebrospinal fluid (CSF) abnormalities in syphilis underwent the mental alternation test (MAT), venipuncture, and lumbar puncture.

Neurosyphilis and the impact of HIV infection.

Neurosyphilis is a complication of systemic syphilis. This review of the clinical presentation, diagnostic laboratory findings, treatment and management of neurosyphilis discusses the impact of HIV and the specific challenges it brings, focusing on areas of controversy, and highlighting important questions that remain to be answered.

Point-of-care treponemal tests for neurosyphilis diagnosis.

Background: The laboratory diagnosis of neurosyphilis rests upon identifying cerebrospinal fluid (CSF) abnormalities, including CSF-Venereal Disease Research Laboratory (VDRL) reactivity. The CSF-VDRL may not be available in the parts of the world where neurosyphilis is most common. Treponemal immunochromatographic strip tests (ICSTs) have been developed as point-of-care tests on blood for syphilis diagnosis in resource-limited settings.

Toll-like receptor polymorphisms are associated with increased neurosyphilis risk.

Background: Single-nucleotide polymorphisms (SNPs) in toll-like receptors (TLR) 1, 2, and 6 impair cell signaling in response to spirochetal lipoproteins. We investigated whether common SNPs in TLR1, TLR2, or TLR6 were associated with laboratory- or clinically-defined neurosyphilis.

Methods: Polymorphisms in the genes for TLR1 (a T→G mutation at position 1805), TLR2 (a G→A mutation at position 2258), and TLR6 (a C→T mutation at position 745) were sought in 456 white patients with syphilis.

Peripheral neuropathy in primary HIV infection associates with systemic and central nervous system immune activation.

Background: Peripheral neuropathy (PN) is a frequent complication of chronic HIV infection. We prospectively studied individuals with primary HIV infection (<1 year after transmission) to assess the presence of and laboratory associations with PN in this early stage.

Methods: Standardized examination and analysis of blood and cerebrospinal fluid (CSF) was performed in participants with laboratory-confirmed primary HIV infection.

Central nervous system diseases due to opportunistic and coinfections.

With the widespread use of combination antiretroviral therapy (cART), the incidence of central nervous system (CNS) opportunistic infections and coinfections has significantly decreased. This review focuses on the clinical presentation, diagnostic laboratory and radiologic findings, as well as the treatment of neurosyphilis, progressive multifocal leukoencephalopathy, primary CNS lymphoma, and toxoplasmosis, which are CNS opportunistic infections and coinfections that are most relevant to clinicians in North America.

Cellular Composition of Cerebrospinal Fluid in HIV-1 Infected and Uninfected Subjects.

In order to characterize the cellular composition of cerebrospinal fluid (CSF) in a healthy state and in the setting of chronic pleocytosis associated with HIV-1 (HIV) infection, multi-parameter flow cytometry was used to identify and quantitate cellular phenotypes in CSF derived from HIV-uninfected healthy controls and HIV-infected subjects across a spectrum of disease and treatment. CD4+ T cells were the most frequent CSF population and the CD4:CD8 ratio was significantly increased in the CSF compared to blood (p = 0.0232), suggesting preferential trafficking of CD4+ over CD8+ T cells to this compartment.

CD57 expression and cytokine production by T cells in lesional and unaffected skin from patients with psoriasis.

Background: The immunopathogenic mechanisms leading to psoriasis remain unresolved. CD57 is a marker of replicative inability and immunosenescence on CD8+ T cells and the proportion of CD57 expressing CD8+ T cells is increased in a number of inflammatory conditions.

Methodology: We examined the expression of CD57 on T cells in the skin of patients affected with psoriasis, comparing lesional and unaffected skin.

Skewed distribution of natural killer cells in psoriasis skin lesions.

Psoriasis is a hyper-proliferative disease of the skin in which immunological mechanisms play a direct pathogenetic role. There have been limited studies of natural killer (NK) cells in psoriasis. The aim of this study was to examine the phenotype of NK cells in skin biopsies and peripheral blood mononuclear cells from patients with psoriasis and healthy controls.

Infectious etiologies of myelopathy.

Myelopathy refers to a spinal cord disorder that presents with motor and/or sensory deficits. Infectious agents that cause myelopathy do so by either direct infection of neural structures (e.g.

The rapid plasma reagin test cannot replace the venereal disease research laboratory test for neurosyphilis diagnosis.

Background: The cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL) test is a mainstay for neurosyphilis diagnosis, but it lacks diagnostic sensitivity and is logistically complicated. The rapid plasma reagin (RPR) test is easier to perform, but its appropriateness for use on CSF is controversial.

Methods: RPR reactivity was determined for CSF from 149 individuals with syphilis using 2 methods.

Expansion of CD8+ T cells lacking Sema4D/CD100 during HIV-1 infection identifies a subset of T cells with decreased functional capacity.

Sema4D, also known as CD100, is a constitutively expressed immune semaphorin on T cells and NK cells. CD100 has important immune regulatory functions that improve antigen-specific priming by antigen-presenting cells, and can also act as a costimulatory molecule on T cells. We investigated the consequence of HIV-1 infection on CD100 expression by T cells, and whether CD100 expression signifies functionally competent effector cells.

Syphilis: using modern approaches to understand an old disease.

Syphilis is a fascinating and perplexing infection, with protean clinical manifestations and both diagnostic and management ambiguities. Treponema pallidum subsp. pallidum, the agent of syphilis, is challenging to study in part because it cannot be cultured or genetically manipulated.

Minocycline fails to modulate cerebrospinal fluid HIV infection or immune activation in chronic untreated HIV-1 infection: results of a pilot study.

Background: Minocycline is a tetracycline antibiotic that has been shown to attenuate central nervous system (CNS) lentivirus infection, immune activation, and brain injury in model systems. To initiate assessment of minocycline as an adjuvant therapy in human CNS HIV infection, we conducted an open-labelled pilot study of its effects on cerebrospinal fluid (CSF) and blood biomarkers of infection and immune responses in 7 viremic subjects not taking antiretroviral therapy.

Results: There were no discernable effects of minocycline on CSF or blood HIV-1 RNA, or biomarkers of immune activation and inflammation including: CSF and blood neopterin, CSF CCL2, CSF white blood cell count, and expression of cell-surface activation markers on CSF and blood T lymphocytes and monocytes.

Altered mental status in HIV-infected patients.

HIV-infected patients are vulnerable to developing altered mental status (AMS) for myriad reasons, including the effects of HIV itself, the accompanying immune dysfunction, associated systemic illness, comorbid psychiatric disorders, and complicated medication regimens. Combination antiretroviral therapy (ART) has decreased the incidence of central nervous system (CNS) opportunistic infections (OIs) and HIV-associated dementia, but the benefits are not absolute. In addition to CNS OIs and complications of complex multisystem disease, immune reconstitution events developing in the early weeks and months after initiating ART may affect the brain and cause AMS.

Increased number and function of natural killer cells in human immunodeficiency virus 1-positive subjects co-infected with herpes simplex virus 2.

Natural killer (NK) cells bridge the interface between innate and adaptive immunity and are implicated in the control of herpes simplex virus 2 (HSV-2) infection. In subjects infected with human immunodeficiency virus 1 (HIV-1), the critical impact of the innate immune response on disease progression has recently come into focus. Higher numbers of NK cells are associated with lower HIV-1 plasma viraemia.

Cerebrovascular complications of methamphetamine abuse.

Objective: Methamphetamine is a stimulant widely abused in the United States. The objective of this study was to demonstrate an association of methamphetamine use and ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage and to further reveal the underlying vascular pathology using neuroimaging and pathology.

Methods: This was a retrospective study based on medical chart review of admissions to the neurovascular service of a tertiary care medical center from January 2003 to July 2007.

Natural killer cell-mediated lysis of dorsal root ganglia neurons via RAE1/NKG2D interactions.

Natural killer cells have been reported to be able to kill various transformed and virus-infected target cells. It was recently observed that NK cells also could kill syngeneic dorsal root ganglia (DRG) neurons by a perforin-dependent mechanism. We demonstrate here that this phenomenon does not reflect a general ability of NK cells to kill neurons in culture.

NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation.

NKG2D is a receptor on natural killer (NK) cells and cytotoxic T lymphocytes that binds major histocompatibility complex (MHC) class I-like ligands expressed primarily on virally infected and neoplastic cells. In vitro studies indicate that NKG2D provides costimulation through an associated adapter, DAP10, which recruits phosphatidylinositol-3 kinase. Here we show that in DAP10-deficient mice, CD8+ T cells lack NKG2D expression and are incapable of mounting tumor-specific responses.