title: Evolution of broadly cross-reactive HIV-1-neutralizing activity: therapy-associated decline, positive association with detectable viremia, and partial restoration of B-cell subpopulations.
abstract: Little is known about the stability of HIV-1 cross-neutralizing responses. Taking into account the fact that neutralization breadth has been positively associated with plasma viral load, there is no explanation for the presence of broadly neutralizing responses in a group of patients on treatment with undetectable viremia. In addition, the B-cell profile responsible for broadly cross-neutralizing responses is unknown. Here we studied the evolution of neutralizing responses and the B-cell subpopulation distribution in a group of patients with broadly cross-reactive HIV-1-neutralizing activity. We studied neutralization breadth evolution in a group of six previously identified broadly cross-neutralizing patients and six control patients during a 6-year period with a previously described minipanel of recombinant viruses from five different subtypes. B-cell subpopulation distribution during the study was also determined by multiparametric flow cytometry. Broadly cross-neutralizing activity was transient in four broad cross-neutralizers and stable, up to 4.6 years, in the other two. In four out of five broad cross-neutralizers who initiated treatment, a neutralization breadth loss occurred after viremia had been suppressed for as much as 20 months. B-cell subpopulation analyses revealed a significant increase in the frequency of naive B cells in broadly cross-reactive samples, compared with samples with less neutralization breadth (increased from 44% to 62%). We also observed a significant decrease in tissue-like and activated memory B cells (decreased from 19% to 12% and from 17% to 9%, respectively). Our data suggest that HIV-1 broadly cross-neutralizing activity is variable over time and associated with detectable viremia and partial B-cell restoration.
authors.affiliation: AIDS Research Unit, Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Carolina B
authors.initials: CB
authors.lastname: Ferreira
authors.forename: Alberto
authors.initials: A
authors.lastname: Merino-Mansilla
authors.forename: Anuska
authors.initials: A
authors.lastname: Llano
authors.forename: Ignacio
authors.initials: I
authors.lastname: Pérez
authors.forename: Isabel
authors.initials: I
authors.lastname: Crespo
authors.forename: Laia
authors.initials: L
authors.lastname: Llinas
authors.forename: Felipe
authors.initials: F
authors.lastname: Garcia
authors.forename: Jose M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Eloisa
authors.initials: E
authors.lastname: Yuste
authors.forename: Victor
authors.initials: V
authors.lastname: Sanchez-Merino
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000821:virology*; D005075:Biological Evolution; D016022:Case-Control Studies; D003429:Cross Reactions; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D015483:HIV Antibodies / Q000276:immunology* / Q000627:therapeutic use; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D019562:Viral Load; D014766:Viremia / Q000235:genetics / Q000821:virology*
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies