title: Longitudinal Analysis of Cerebrospinal Fluid and Plasma HIV-1 Envelope Sequences Isolated From a Single Donor with HIV Asymptomatic Neurocognitive Impairment.
abstract: OBJECTIVE
  Combined antiretroviral treatment (cART) has changed the clinical presentation of HIV-associated neurocognitive disorders (HAND) to that of the milder forms of the disease. Asymptomatic neurocognitive impairment (ANI) is now more prevalent and is associated with increased morbidity and mortality risk in HIV-1-infected people. HIV-1 envelope (env) genetic heterogeneity has been detected within the central nervous system (CNS) of individuals with ANI. Changes withinenvdetermine co-receptor use, cellular tropism, and neuropathogenesis. We hypothesize that compartmental changes are associated with HIV-1envC2V4 during ANI and sought to analyze paired HIV-1envsequences from plasma and cerebrospinal fluid (CSF) of a female subject undergoing long-term cART.
  
  
  METHODS
  Paired plasma and CSF samples were collected at 12-month intervals and HIV-1envC2V4 was cloned and sequenced.
  
  
  RESULTS
  Phylogenetic analysis of paired samples consistently showed genetic variants unique to the CSF. Phenotypic prediction showed CCR5 (R5) variants for all CSF-derived sequences and showed minor X4 variants (or dual-tropic) in the plasma at later time points. Viral compartmentalization was evident throughout the study, suggesting that the occurrence of distinctiveenvstrains may contribute to the neuropathogenesis of HAND.
  
  
  CONCLUSIONS
  Our study provides new insights about the genetic characteristics within the C2V4 of HIV-1envthat persist after long-term cART and during the course of persistent ANI.
authors.affiliation: Department of Microbiology, Ponce Health Sciences University- School of Medicine/Ponce Research Institute, Ponce, PR 00716, USA.
authors.forename: Fabián
authors.initials: F
authors.lastname: Vázquez-Santiago
authors.affiliation: Department of Microbiology, Ponce Health Sciences University- School of Medicine/Ponce Research Institute, Ponce, PR 00716, USA.
authors.forename: Yashira
authors.initials: Y
authors.lastname: García
authors.affiliation: Department of Microbiology, Ponce Health Sciences University- School of Medicine/Ponce Research Institute, Ponce, PR 00716, USA.
authors.forename: Ivelisse
authors.initials: I
authors.lastname: Rivera-Román
authors.affiliation: Department of Biochemistry, Ponce Health Sciences University- School of Medicine/Ponce Research Institute, Ponce, PR 00716, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Noel
authors.affiliation: Specialized NeuroAIDS Program, University of Puerto Rico-Medical Sciences Campus, San Juan, PR, 00936, USA ; Department of Internal Medicine, Neurology Division, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00936, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Wojna
authors.affiliation: Specialized NeuroAIDS Program, University of Puerto Rico-Medical Sciences Campus, San Juan, PR, 00936, USA ; Department of Microbiology and Medical Zoology, University of Puerto Rico-Medical Sciences Campus, San Juan, PR, 00936, USA.
authors.forename: Loyda M
authors.initials: LM
authors.lastname: Meléndez
authors.affiliation: Department of Microbiology, Ponce Health Sciences University- School of Medicine/Ponce Research Institute, Ponce, PR 00716, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Rivera-Amill
keywords: HAND; HIV; asymptomatic neurocognitive impairment; cerebrospinal fluid; envelope; evolution; plasma