title: Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection.
abstract: BACKGROUND
  Neutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment. The patients included participated in the Primo-SHM trial where patients with an early HIV-1 infection were randomized to no treatment or treatment for 24 or 60 weeks.
  
  
  METHODS
  Primo-SHM trial patients selected for the present study were untreated (n = 23) or treated for 24 weeks (n = 24). Here we investigate memory B cell properties at viral set-point and at a late time point (respectively median 54 and 73 weeks) before (re)-initiation of treatment.
  
  
  RESULTS
  At viral set-point, the memory B cell compartment in treated patients demonstrated significantly lower fractions of antigen-primed, activated, memory B cells (p = 0.006). In contrast to untreated patients, in treated patients the humoral HIV-specific response reached a set point over time. At a transcriptional level, sets of genes that showed enhanced expression in memory B cells at viral setpoint in untreated patients, conversely showed rapid increase of expression of the same genes in treated patients at the late time point.
  
  
  CONCLUSIONS
  These data suggest that, although the memory B cell compartment is phenotypically preserved until viral setpoint after treatment interruption, the development of the HIV-specific antibody response may benefit from exposure to HIV. The effect of viral exposure on B cell properties is also reflected by longitudinal changes in transcriptional profile in memory B cells over time in early treated patients.
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands.|Institute for Global Health and Development, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Godelieve J
authors.initials: GJ
authors.lastname: de Bree
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Adam K
authors.initials: AK
authors.lastname: Wheatley
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Lynch
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Madhu
authors.initials: M
authors.lastname: Prabhakaran
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Marlous L
authors.initials: ML
authors.lastname: Grijsen
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Prins
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Schmidt
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Adrian B
authors.initials: AB
authors.lastname: McDermott
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008875:Middle Aged; D014158:Transcription, Genetic