Changes in Cerebrospinal Fluid Proteins across the Spectrum of Untreated and Treated Chronic HIV-1 Infection.

Using the platform, we measured 1,463 unique proteins in 303 cerebrospinal fluid (CSF) specimens from four clinical centers that included uninfected controls and 12 groups of people living with HIV-1 infection representing the spectrum of progressive untreated and treated chronic infection. We present three initial analyses of these measurements: an overview of the CSF protein features of the sample; correlations of the CSF proteins with CSF HIV-1 RNA and neurofilament light chain protein (NfL) concentrations; and comparison of the CSF proteins in HIV-associated dementia ( ) and neurosymptomatic CSF escape ( ). These reveal a complex but coherent picture of CSF protein changes that includes highest concentrations of many proteins during CNS injury in the and groups and variable protein changes across the course of neuroasymptomatic systemic HIV-1 progression, including two common patterns, designated as and patterns, related to the principal involvement of their underlying inflammatory cell lineages.

Infection and inflammation: New perspectives on Alzheimer's disease.

Neuroinflammation has been recognized as a component of Alzheimer's Disease (AD) pathology since the original descriptions by Alois Alzheimer and a role for infections in AD pathogenesis has long been hypothesized. More recently, this hypothesis has gained strength as human genetics and experimental data suggest key roles for inflammatory cells in AD pathogenesis. To review this topic, Duke/University of North Carolina (Duke/UNC) Alzheimer's Disease Research Center hosted a virtual symposium: "Infection and Inflammation: New Perspectives on Alzheimer's Disease (AD).

HIV Disease Dynamics and Markers of Inflammation and CNS Injury During Primary HIV Infection and Their Relationship to Cognitive Performance.

Introduction: Early systemic and central nervous system viral replication and inflammation may affect brain integrity in people with HIV, leading to chronic cognitive symptoms not fully reversed by antiretroviral therapy (ART). This study examined associations between cognitive performance and markers of CNS injury associated with acute HIV infection and ART.

Methods: HIV-infected MSM and transgender women (average age: 27 years and education: 13 years) enrolled within 100 days from the estimated date of detectable infection (EDDI).

RETRACTED: Remission of Subacute Psychosis in a COVID-19 Patient With an Antineuronal Autoantibody After Treatment With Intravenous Immunoglobulin.

Retraction notice to: “Remission of Subacute Psychosis in a COVID-19 Patient With an Antineuronal Autoantibody After Treatment With Intravenous Immunoglobulin” by Lindsay S. McAlpine, Brooke Lifland, Joseph R. Check, Gustavo A.

Feasibility and safety of research sigmoid colon biopsy in a cohort of Thai men who have sex with men with acute HIV-1.

Background: The gut-associated lymphoid tissue (GALT) is a major reservoir of HIV-1 established early in acute HIV-1 infection (AHI). Sampling tissue from GALT can provide information about viral reservoirs and immune responses but may be complicated during AHI for reasons such as high viral replication, CD4 T cell depletion and immune activation. Risk of adverse events (AEs) associated with research sigmoid colon biopsies was assessed in participants with AHI in Bangkok, Thailand.

Markers of CNS Injury in Adults Living With HIV With CSF HIV Not Detected vs Detected <20 Copies/mL.

The presence of quantifiable HIV RNA in cerebrospinal fluid (CSF) during antiretroviral therapy (ART) can associate with central nervous system (CNS) pathology, but the significance of RNA detected below the limit of quantification (LOQ) on a standard assay during ART remains unknown. We compared CNS parameters between individuals with CSF RNA detected below the LOQ (20 copies/mL) with those with HIV RNA not detected. Detection of CSF HIV RNA associated with decreased blood-brain barrier integrity and with decreased executive function, but not with CNS immune activation or poorer performance in overall neuropsychological testing.

Brief Report: Safety and Tolerability of Inguinal Lymph Node Biopsy in Individuals With Acute HIV Infection in Thailand.

Introduction: Latent HIV reservoirs are rapidly established in lymphoid tissues during acute HIV infection (AHI). Sampling these tissues provides important information about HIV pathogenesis. This period is associated with viral replication and immune activation that may affect procedure-related adverse events (AEs).

Global Health Neurology: HIV/AIDS.

With the advent of combination antiretroviral therapies, the mortality rate from HIV has declined, while the prevalence of long-term HIV-related neurologic complications continues to rise. Thirty-six million individuals are living with HIV around the world, many of whom reside in resource-limited settings. The majority of studies have focused on individuals residing in the developed world, while the impact of HIV disproportionately affects people living in developing countries.

CROI 2017: Neurologic Complications of HIV Infection.

The brain is a major target for HIV infection and is a potential viral reservoir even in virologically well-controlled HIV-infected individuals. Data presented at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) suggested that during early HIV infection, CD4+ T cells in the meninges and choroid plexus serve as an important early site of HIV infection in the central nervous system (CNS), with brain macrophages and microglial cells becoming an important source of viral replication with advancing disease. Longitudinal evaluations of HIV-associated neurocognitive disorder (HAND) demonstrated that cognitive changes occur during early HIV infection and may remain during chronic infection despite virologic control by antiretroviral therapy.

HIV-Associated Neurologic Disorders and Central Nervous System Opportunistic Infections in HIV.

Since the advent of combination antiretroviral therapy (cART), HIV has transformed from a fatal disease to a chronic illness that often presents with milder central nervous system (CNS) symptoms laced with related confounders. The immune recovery associated with access to cART has led to a new spectrum of immune-mediated presentations of infection, phenotypically distinct from the conditions observed in advanced disease.HIV-associated neurocognitive disorder (HAND) entails a categorized continuum of disorders reflecting an array of clinical presentation, outcome, and increasing level of severity: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD).

CROI 2016: Neurologic Complications of HIV Infection.

The brain remains a major target for HIV infection and a site of potential complications for HIV-infected individuals. Emerging data presented at the 2016 Conference on Retroviruses and Opportunistic Infections suggest that during the early stages of infection, activated CD4+ cells may traffic the virus into the central nervous system (CNS). HIV is detectable in cells and tissues of the CNS in some individuals despite suppressive antiretroviral treatment.

Putamen volume and its clinical and neurological correlates in primary HIV infection.

Objective: Little is known about the extent of cortical and subcortical volumetric alterations that may occur within the first year of HIV infection [primary HIV infection (PHI)].

Design: We used structural MRI in this prospective cross-sectional neuroimaging study to determine the extent of volumetric changes in early HIV infection.

Methods: Cerebrospinal fluid, blood, neuropsychological testing, and structural T1 MRI scans were acquired from 18 HIV and 47 PHI age-matched antiretroviral-naïve male participants.

Immune Activation and HIV-Specific CD8(+) T Cells in Cerebrospinal Fluid of HIV Controllers and Noncontrollers.

The central nervous system (CNS) is an important target of HIV, and cerebrospinal fluid (CSF) can provide a window into host-virus interactions within the CNS. The goal of this study was to determine whether HIV-specific CD8(+) T cells are present in CSF of HIV controllers (HC), who maintain low to undetectable plasma viremia without antiretroviral therapy (ART). CSF and blood were sampled from 11 HC, defined based on plasma viral load (VL) consistently below 2,000 copies/ml without ART.

Immune activation in the central nervous system throughout the course of HIV infection.

Purpose Of Review: Robust and dynamic innate and adaptive responses characterize the acute central nervous system (CNS) response to HIV and other viral infections. In a state of chronic infection or viral latency, persistent immune activation associates with abnormality in the CNS. Understanding this process is critical, as immune-mediated abnormality in nonrenewable CNS cells may result in long-term neurologic sequelae for HIV-infected individuals.

Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV.

Objective: To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+).

Design: 24-week randomized open-label prospective evaluation.

CROI 2015: Neurologic Complications of HIV Infection.

More than 30 years into the HIV epidemic, research efforts are focusing on better understanding how the central nervous system (CNS) is adversely affected by HIV and on improving the quality of life of HIV-infected individuals. At the 2015 Conference on Retroviruses and Opportunistic Infections, neurologic presentations concentrated on characterization of potential CNS reservoirs of HIV, the pathogenesis of HIV-associated neurocognitive disorders (HAND), diagnosis of cognitive dysfunction caused by HIV,neuroimaging biomarkers of HAND, and treatment of modifiable risk factors of HAND. Studies presented also highlighted research on CNS disorders in international, resource-limited settings, setting the stage for a growing collection of collaborative studies that will directly impact the largest concentrations of people living with HIV worldwide.

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.

Cerebrospinal fluid (CSF) neuronal biomarkers across the spectrum of HIV infection: hierarchy of injury and detection.

The character of central nervous system (CNS) HIV infection and its effects on neuronal integrity vary with evolving systemic infection. Using a cross-sectional design and archived samples, we compared concentrations of cerebrospinal fluid (CSF) neuronal biomarkers in 143 samples from 8 HIV-infected subject groups representing a spectrum of untreated systemic HIV progression and viral suppression: primary infection; four groups of chronic HIV infection neuroasymptomatic (NA) subjects defined by blood CD4+ T cells of >350, 200-349, 50-199, and <50 cells/µL; HAD; treatment-induced viral suppression; and 'elite' controllers. Samples from 20 HIV-uninfected controls were also examined.

CROI 2014: Neurologic complications of HIV infection.

A shift in focus in the field of neuroHIV was clearly manifest at the 2014 Conference on Retroviruses and Opportunistic Infections (CROI), where a major emphasis was on the milder forms of neurologic morbidity, including cognitive impairment, seen in well-treated patients. Mechanisms of this persistent abnormality were investigated, including extensive analysis of the prevalence and associations of persistent HIV detection in cerebrospinal fluid (CSF) and characterization of persistent CNS immune activation. Another key emphasis was the early establishment of HIV replication and inflammation within the central nervous system (CNS) and the potentially salutary effect of very early HIV diagnosis and treatment in protecting the CNS from HIV-related injury.

Evolving character of chronic central nervous system HIV infection.

Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) begins early in systemic infection and continues throughout its untreated course. Despite a common cerebrospinal fluid inflammatory response, it is usually neurologically asymptomatic for much of this course, but can evolve in some individuals to HIV-associated dementia (HAD), a severe encephalopathy with characteristic cognitive and motor dysfunction. While widespread use of combination antiretroviral therapy (ART) has led to a marked decline in both the CNS infection and its neurologic severe consequence, HAD continues to afflict individuals presenting with advanced systemic infection in the developed world and a larger number in resource-poor settings where ART is more restricted.