title: Association of a pool of HIV-1 with erythrocytes in vivo: a cohort study.
abstract: BACKGROUND
  Treatment of HIV-1-infected individuals with antiretrovirals can result in sustained suppression of plasma viral RNA at concentrations below the detection limit of available assays. However, continuing virus replication has been detected in patients with viral RNA in plasma suppressed for months to years, and many cell types are known to act as reservoirs or carriers for the virus. In vitro, erythrocytes bind HIV-1 immune complexes, so we tested for a circulating pool of HIV-1 associated with erythrocytes in people with HIV-1 infection.
  
  
  METHODS
  We investigated 82 chronically HIV-1-infected individuals. Plasma, white cells, and erythrocytes were tested for HIV-1 RNA by RT-PCR.
  
  
  RESULTS
  Erythrocyte-associated HIV-1 RNA was detected in 80 of 82 individuals. In 23, plasma HIV-1 RNA had been undetectable (<20 copies/mL) for up to 32 months; in corresponding erythrocyte samples, there were up to 82878 HIV-1 RNA copies per mL whole blood. HIV-1 associated with erythrocytes in vivo was shown to be infectious. Within the subgroup of patients with undetectable plasma viral load, higher numbers of HIV-1 associated with erythrocytes were correlated with a history of advanced clinical stages of HIV-1 infection (p=0.014).
  
  
  CONCLUSIONS
  A pool of HIV-1 is associated with erythrocytes even after long-term suppression of viral RNA in plasma. This finding is direct evidence for continuing virus replication or release in these individuals. Quantification of this viral pool may help to judge suppression of HIV-1 replication in individuals with undetectable plasma HIV-1 RNA.
authors.affiliation: Department of Research, Immunonephrology Laboratory, University Hospital Basel, Basel, Switzerland. christoph.hess@unibas.ch
authors.forename: Christoph
authors.initials: C
authors.lastname: Hess
authors.forename: Thomas
authors.initials: T
authors.lastname: Klimkait
authors.forename: Luregn
authors.initials: L
authors.lastname: Schlapbach
authors.forename: Veronika
authors.initials: V
authors.lastname: Del Zenero
authors.forename: Salima
authors.initials: S
authors.lastname: Sadallah
authors.forename: Eliska
authors.initials: E
authors.lastname: Horakova
authors.forename: Gianmarco
authors.initials: G
authors.lastname: Balestra
authors.forename: Verena
authors.initials: V
authors.lastname: Werder
authors.forename: Christoph
authors.initials: C
authors.lastname: Schaefer
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Jürg-Alfred
authors.initials: JA
authors.lastname: Schifferli
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D004912:Erythrocytes / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D015497:HIV-1; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012367:RNA, Viral