title: HIV-associated neurocognitive disorder is associated with HIV-1 dual infection.
abstract: Compared with HIV monoinfection, HIV dual infection has been associated with decreased CD4 T-cell counts and increased viral loads. The same markers are also associated with the development of HIV-associated neurocognitive disorder (HAND), which continues to be a prevalent problem in the era of combination antiretroviral therapy (ART). We sought to determine the relationship between dual infection and HAND.
  
  
  
  Participants on ART (N = 38) underwent deep sequencing of four PCR-amplified HIV coding regions derived from peripheral blood mononuclear cell DNA samples. Phylogenetic analyses were performed to evaluate whether two distinct viral lineages, that is, dual infection, were present in the same individual. All study participants underwent neurocognitive, substance use, and neuromedical assessments at each study visit.
  
  
  
  Of 38 participants, nine (23.7%) had evidence of dual infection. Using clinical ratings, global neurocognitive impairment was identified in 21 (55%) participants, and multivariate analysis demonstrated a significant association between dual infection and impairment; odds ratio (95% confidence interval) = 18.3 (1.9, 414.2), P = 0.028. Neurocognitive impairment was also associated with lower current (P = 0.028) and nadir (P = 0.043) CD4 T-cell counts.
  
  
  
  Deep sequencing of HIV DNA populations in blood mononuclear cell identified dual infection in nearly a quarter of HIV-infected adults receiving ART, and dual infection was associated with HAND. Dual infection may contribute to the development of HAND, perhaps because of increased viral diversity. Further investigation is needed to determine how dual infection results in worse neurocognitive performance.
authors.affiliation: aUniversity of California, San Diego, La Jolla, California, USA bINSERM UMR U966, Tours, France cVeterans Affairs San Diego Healthcare System, San Diego, California, USA.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Wagner
authors.forename: Antoine
authors.initials: A
authors.lastname: Chaillon
authors.forename: Siqi
authors.initials: S
authors.lastname: Liu
authors.forename: Donald R
authors.initials: DR
authors.lastname: Franklin
authors.forename: Gemma
authors.initials: G
authors.lastname: Caballero
authors.forename: Sergei L
authors.initials: SL
authors.lastname: Kosakovsky Pond
authors.forename: Florin
authors.initials: F
authors.lastname: Vaida
authors.forename: Robert K
authors.initials: RK
authors.lastname: Heaton
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
mesh_terms: D015526:AIDS Dementia Complex / Q000453:epidemiology* / Q000209:etiology*; D060085:Coinfection / Q000150:complications* / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006678:HIV / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D015658:HIV Infections / Q000150:complications* / Q000821:virology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D000073216:Mental Status and Dementia Tests; D008875:Middle Aged; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies
chemical_list: D004279:DNA, Viral