The Johns Hopkins NIMH Center comprises an interdisciplinary research team who has pooled their talents to study the nature of HIV-associated neurocognitive disorders (HAND). Their aim is to translate discoveries of the pathophysiological mechanisms into novel therapeutics for HAND.
Abstract: Neurologic complications for HIV-infected persons retain significant prevalence despite an increasingly global use of antiretroviral therapies. Such complications are often ascribed to advanced immunosuppression; however, the most common neurologic problems for HIV-infected persons, distal sensory polyneuropathy and HIV-associated neurocognitive disorders, affect a significant proportion of patients who have successfully achieved immunologic restoration with normal or near-normal CD4 count levels and undetectable HIV RNA in the periphery. Understanding specificconsiderations for HIV-associated complications, including the epidemiology, risk factors, medication-adverse effects, and benefits of appropriate management, is vital for all providers caring for those with HIV. This review will describe such considerations, as well as providing a more detailed review of the most common neurologic complications of HIV infection, and will highlight some of the challenges involved with diagnosis, management, and long-term effects.
Fig. 1: Different mechanisms (cerebrovascular disease, amyloid deposition, and comorbidities) for varied age groups may contribute to decreased brain reserve that promulgates HIV-associated neurocognitive disorders. Courtesy of Ned Sacktor, MD
Identification of Putative Biomarkers for HIV-associated Neurocognitive Impairment in the CSF of HIV-infected Patients under cART Therapy Determined by Mass Spectrometry�
Journal of Neuroviology. 2014. 20(5):457-465
Abstract: We identified and measured proteins in the cerebral spinal fluid (CSF) involved in HIV-associated neurological disorders. Protein levels were determined by mass spectrometry (MS) in pooled CSF taken from three patient groups (human immunodeficiency virus (HIV)-1-infected patients that developed HIV-associated neurocognitive disorders (HANDs), HIV-1-infected patients without HAND, and healthy controls). Pools were generated from 10 patients each per group. CSF from individual patient groups were digested with trypsin and separately labeled using with isobaric tags for relative and absolute quantitation (iTRAQ). After combining all samples in one, peptides were extensively fractionated by offline two-dimensional separation and identified by tandem MS. One hundred and ninety three proteins were deemed to be interpretable for quantitation based on permutation tests with a 95 % confidence interval with a p value ≤ 0.05. Using a cutoff of 1.5-fold for upregulation and 0.6 for downregulation, 16 proteins were differentially expressed in HIV + HAND (reporter p value ≤0.05) with seven of them previously described as HIV-interacting proteins: endoplasmin, mitochondrial damage mediator-BH3-interacting domanin death agonist, orosomucoid, apolipoprotein E, metalloproteinase inhibitor 2, peroxiredoxin-2, and the nuclear protein, ruvB-like 2. Several previously unidentified proteins with possible neurological implication in HIV patients include forming-binding protein 1, C-reactive protein, leukocyte-associated immunoglobulin receptor 1, renin receptor, mediator of RNA polymerase II transcription subunit 14, multimerin-2, alpha-N-acetylglucosaminidase, caldesmon, and cadherin EGF LAG G-type receptor. Our results suggest that not only a few but possibly a combination of biomarkers that are highly correlated can predict neurocognitive status in HIV-infected patients and might be involved in monocyte or macrophage activation.
Abstract: Cross-sectional studies show that around half of individuals infected with HIV-1 have some degree of cognitive impairment despite the use of antiretroviral drugs. However, prevalence estimates vary depending on the population and methods used to assess cognitive impairment. Whether asymptomatic patients would beneﬁt from routine screening for cognitive diffculties is unclear and the appropriate screening method and subsequent management is the subject of debate. In some patients, HIV-1 RNA can be found at higher concentrations in CSF than in blood, which potentially results from the poor distribution of antiretroviral drugs into the CNS. However, the clinical relevance of so-called CSF viral escape is not well understood. The extent to which antiretroviral drug distribution and toxicity in the CNS affect clinical decision making is also debated.
Figure 3: Summary of the Frascati criteria for HIV-associated neurocognitive disorders
Broadcasted: October 2014
Clinical and ethical judgment: A profound dilemma
Highlight: The second part of this podcast includes an interview by NIMH Center Director, Justin McArthur, MBBS, MPH, FAAN, discussing salient and clinically relevant features of HIV and its neurologic complications.
Listen to the podcast: Clinical and ethical judgment: A profound dilemma
JHU NIMH CENTER AND COLLABORATOR EVENTS
Webcast URL’s for the Annual NeuroHIV Symposium's morning and afternoon sessions held on Friday, June 19th, 2015:
- Johns Hopkins Faculty and Guest Lecturers present their work at these regularly scheduled conferences:
- Neuroimmunology Seminar Series: Tuesdays (varies), 1:30 p.m., Meyer 1-191 (Resumes September 2015)
- NeuroAIDS Lecture Series: Every Friday, 11 a.m., Meyer 8 Library (Resumes September 2015)
- Collaborator Events:
JHU NIMH Center Directors, investigators, and staff
The Johns Hopkins Center for Novel Therapeutics of HIV-associated Cognitive Disorders is funded by the National Institute of Mental Health, NIMH Grant P30MH075673
Learn more about the NIMH: National Institute of Mental Health / Research on HIV and AIDS