Cerebrospinal Fluid Viral Load and Intrathecal Immune Activation in Individuals Infected with Different HIV-1 Genetic Subtypes

Background: HIV-1 exhibits a high degree of genetic diversity and is presently divided into 3 distinct HIV-1 genetic groups designated major (M), non-M/non-O (N) and outlier (O). Group M, which currently comprises 9 subtypes (A-D, F-H, J and K), at least 34 circulating recombinant forms (CRFs) and several unique recombinant forms (URFs) is responsible for most of the HIV-1 epidemic. Most of the current knowledge of HIV-1 central nervous system (CNS) infection is based on subtype B. However, subtypes other than subtype B account for the majority of global HIV-1 infections. Therefore, we investigated whether subtypes have any influence on cerebrospinal fluid (CSF) markers of HIV-1 CNS infection. Methodology/Principal Findings: CSF HIV-1 RNA, CSF neopterin and CSF white blood cell (WBC) count were measured in patients infected with different HIV-1 subtypes. Using multivariate regression analysis, no differences in the CSF WBC count, neopterin and viral load were found between various HIV-1 subtypes

HIV-1 Nef Protein Structures Associated with Brain Infection and Dementia Pathogenesis

The difference between regional rates of HIV-associated dementia (HAD) in patients infected with different subtypes of HIV suggests that genetic determinants exist within HIV that influence the ability of the virus to replicate in the central nervous system (in Uganda, Africa, subtype D HAD rate is 89%, while subtype A HAD rate is 24%). HIV-1 nef is a multifunctional protein with known toxic effects in the brain compartment. The goal of the current study was to identify if specific three-dimensional nef structures may be linked to patients who developed HAD. HIV-1 nef structures were computationally derived for consensus brain and non-brain sequences from a panel of patients infected with subtype B who died due to varied disease pathologies and consensus subtype A and subtype D sequences from Uganda. Site directed mutation analysis identified signatures in brain structures that appear to change binding potentials and could affect folding conformations of brain-associated structures. Despite the large sequence variation between HIV subtypes, structural alignments confirmed that viral structures derived from patients with HAD were more similar to subtype D structures than to structures derived from patient sequences without HAD. Furthermore, structures derived from brain sequences of patients with HAD were more similar to subtype D structures than they were to their own non-brain structures. The potential finding of a brain-specific nef structure indicates that HAD may result from genetic alterations that alter the folding or binding potential of the protein

An Updated Systematic Review of Neuroimaging Studies of Children and Adolescents with Perinatally Acquired HIV

A recent review of neuroimaging studies related to perinatally acquired human immunodeficiency virus (HIV) infection by Hoare and colleagues (Metabolic Brain Disease 29:221–229, 2014) included studies published between 1995 and 2012, with all but two studies being published in or before 2006. Although the review synthesized the extant research available at the time, the findings may not be relevant to the current population of children and adolescents who are HIV positive due to more recent advances in antiretroviral medication and new medication guidelines. As such, the purpose of this paper was to extend the findings of Hoare and colleagues by reviewing the imaging literature that has been published since 2012 and to compare the more recent studies to the earlier ones. The results were that 11 articles met criteria for inclusion in this review. The majority of studies were cross-sectional and analyzed MRI data.. Samples included children and adolescents of nearly all ages. Studies differed widely on the inclusion and reporting of clinical variables. Imaging was focused primarily on white matter, and white matter issues such as lesions, poor tract integrity, and reduced volume were found in samples of children and adolescents of various age ranges. Two studies compared the cognitive functioning of children with HIV to controls, and both found that children with HIV perform more poorly than their non-infected peers on various cognitive tasks. Based on the findings of this review, recommendations for future imaging research are made

Ultrasound lung "comets" increase after breath-hold diving.

The purpose of the study was to analyze the ultrasound lung comets (ULCs) variation, which are a sign of extra-vascular lung water. Forty-two healthy individuals performed breath-hold diving in different conditions: dynamic surface apnea; deep variable-weight apnea and shallow, face immersed without effort (static maximal and non-maximal). The number of ULCs was evaluated by means of an ultrasound scan of the chest, before and after breath-hold diving sessions. The ULC score increased significantly from baseline after dynamic surface apnea (p = 0.0068), after deep breath-hold sessions (p = 0.0018), and after static maximal apnea (p = 0.031). There was no statistically significant difference between the average increase of ULC scores after dynamic surface apnea and deep breath-hold diving. We, therefore, postulate that extravascular lung water accumulation may be due to other factors than (deep) immersion alone, because it occurs during dynamic surface apnea as well. Three mechanisms may be responsible for this. First, the immersion-induced hydrostatic pressure gradient applied on the body causes a shift of peripheral venous blood towards the thorax. Second, the blood pooling effect found during the diving response Redistributes blood to the pulmonary vascular bed. Third, it is possible that the intense involuntary diaphragmatic contractions occurring during the "struggle phase" of the breath-hold can also produce a blood shift from the pulmonary capillaries to the pulmonary alveoli. A combination of these factors may explain the observed increase in ULC scores in deep, shallow maximal and shallow dynamic apneas, whereas shallow non-maximal apneas seem to be not "ULC provoking".Clinical TrialJournal Articleinfo:eu-repo/semantics/publishe