title: HIV DNA in CD14+ reservoirs is associated with regional brain atrophy in patients naive to combination antiretroviral therapy.
abstract: OBJECTIVE
  To examine associations between regional brain volumes and HIV DNA in peripheral CD14 cells (monocytes) among HIV-infected individuals naive to combination antiretroviral therapy (cART).
  
  
  METHODS
  A prospective study of HIV-infected Thai individuals who met Thai national criteria for cART initiation. Enrolment was stratified by HIV DNA in a blinded fashion.
  
  
  METHODS
  CD14 cells were isolated from peripheral mononuclear cells to high purity (median 91.4% monocytes by flow cytometry), and HIV DNA was quantified by multiplex real-time PCR. Baseline regional brain volumes obtained by T1-weighted 1.5-Tesla MRI were compared between HIV DNA groups using analysis of covariance (ANCOVA).
  
  
  RESULTS
  We studied 60 individuals with mean (SD) age of 34.7 (7.0) years, CD4 T-lymphocyte count of 232 (137) cells/μl and log10 plasma HIV RNA of 4.8 (0.73). Median (interquartile range, IQR) HIV DNA copy number per 10 CD14 cells was 54 (102). Using our previously determined optimal cut-point of 45 copies/10 cells for this cohort, a threshold value above which CD14 HIV DNA identified HIV-associated neurocognitive disorders (HANDs), we found that CD14 HIV DNA  ≥ 45 copies/10 cells was associated with reduced volumes of the nucleus accumbens (P=0.021), brainstem (P=0.033) and total gray matter (P=0.045) independently of age, CD4 cell count and intracranial volume.
  
  
  CONCLUSIONS
  HIV DNA burden in CD14 monocytes is directly linked to brain volumetric loss. Our findings implicate peripheral viral reservoirs in HIV-associated brain atrophy and support their involvement in the neuropathogenesis of HAND, underscoring the need for therapies that target these cells.
authors.affiliation: aUniversity of Hawaii at Manoa, Honolulu, Hawaii bUniversity of California, San Francisco, California, USA cFaculty of Medicine, Chulalongkorn University dPhramongkutklao Hospital eSEARCH, The Thai Red Cross AIDS Research Center fHIV-NAT, The Thai Red Cross AIDS Research Center, Bangkok, Thailand. *Kalpana J. Kallianpur and Victor G. Valcour contributed equally to the writing of the manuscript.
authors.forename: Kalpana J
authors.initials: KJ
authors.lastname: Kallianpur
authors.forename: Victor G
authors.initials: VG
authors.lastname: Valcour
authors.forename: Sukalaya
authors.initials: S
authors.lastname: Lerdlum
authors.forename: Edgar
authors.initials: E
authors.lastname: Busovaca
authors.forename: Melissa
authors.initials: M
authors.lastname: Agsalda
authors.forename: Pasiri
authors.initials: P
authors.lastname: Sithinamsuwan
authors.forename: Thep
authors.initials: T
authors.lastname: Chalermchai
authors.forename: James L K
authors.initials: JL
authors.lastname: Fletcher
authors.forename: Somporn
authors.initials: S
authors.lastname: Tipsuk
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Shikuma
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Shiramizu
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
mesh_terms: D000328:Adult; D044466:Asian People; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008297:Male; D009000:Monocytes / Q000737:chemistry / Q000276:immunology / Q000821:virology*; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D013785:Thailand; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D018950:Lipopolysaccharide Receptors