title: Absence of reproducibly detectable low-level HIV viremia in highly exposed seronegative men and women.
abstract: OBJECTIVE
  Transient HIV infections have been invoked to account for the cellular immune responses detected in highly virus-exposed individuals who have remained HIV-seronegative. We tested for very low levels of HIV RNA in 524 seronegative plasma samples from 311 highly exposed women and men from three longitudinal HIV cohorts.
  
  
  METHODS
  Two thousand and seventy-three transcription-mediated amplification (TMA) HIV RNA tests were performed for an average of 3.95 TMA assays per plasma sample. Quadruplicate TMA assays, analyzing a total of 2 ml of plasma, provided an estimated sensitivity of 3.5 HIV RNA copies/ml.
  
  
  RESULTS
  Four samples from individuals who did not seroconvert within the following 6 months were positive for HIV RNA. For one sample, human polymorphism DNA analysis indicated a sample mix-up. Borderline HIV RNA detection signals were detected for the other three positive samples but further replicate TMA testing yielded no positive results. Nested PCR assays (n = 254) for HIV proviral DNA in peripheral blood mononuclear cells (PBMCs) from these three individuals were negative.
  
  
  CONCLUSIONS
  Transient viremia was not reproducibly detected in highly HIV-exposed seronegative men and women. If transient infections do occur, plasma HIV RNA levels may remain below the detection limits of the sensitive assay used here, be of very short duration, or viral replication may be restricted to mucosal surfaces or their draining lymphoid tissues.
authors.affiliation: Blood Systems Research Institute, University of California, San Francisco, USA. delwarte@medicine.ucsf.edu
authors.forename: Eric
authors.initials: E
authors.lastname: Delwart
authors.forename: Flavien
authors.initials: F
authors.lastname: Bernardin
authors.forename: Tzong-Hae
authors.initials: TH
authors.lastname: Lee
authors.forename: Valerie
authors.initials: V
authors.lastname: Winkelman
authors.forename: Chenglong
authors.initials: C
authors.lastname: Liu
authors.forename: Haynes
authors.initials: H
authors.lastname: Sheppard
authors.forename: Albert
authors.initials: A
authors.lastname: Liu
authors.forename: Ruth
authors.initials: R
authors.lastname: Greenblatt
authors.forename: Katryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Jack
authors.initials: J
authors.lastname: DeHovitz
authors.forename: Marek
authors.initials: M
authors.lastname: Nowicki
authors.forename: Mardge
authors.initials: M
authors.lastname: Cohen
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Golub
authors.forename: Jason
authors.initials: J
authors.lastname: Barbour
authors.forename: Susan
authors.initials: S
authors.lastname: Buchbinder
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
mesh_terms: D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000276:immunology / Q000821:virology; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D015203:Reproducibility of Results; D014766:Viremia / Q000276:immunology*; D014779:Virus Replication