title: Effect of natural and ARV-induced viral suppression and viral breakthrough on anti-HIV antibody proportion and avidity in patients with HIV-1 subtype B infection.
abstract: BACKGROUND
  Viral suppression and viral breakthrough impact the humoral immune response to HIV infection. We evaluated the impact of viral suppression and viral breakthrough on results obtained with two cross-sectional HIV incidence assays.
  
  
  METHODS
  All samples were collected from adults in the US who were HIV infected for >2 years. Samples were tested with the BED capture enzyme immunoassay (BED-CEIA) which measures the proportion of IgG that is HIV-specific, and with an antibody avidity assay based on the Genetic Systems 1/2+ O ELISA. We tested 281 samples: (1) 30 samples from 18 patients with natural control of HIV-1 infection known as elite controllers or suppressors (2) 72 samples from 18 adults on antiretroviral therapy (ART), with 1 sample before and 2-6 samples after ART initiation, and (3) 179 samples from 20 virally-suppressed adults who had evidence of viral breakthrough receiving ART (>400 copies/ml HIV RNA) and with subsequent viral suppression.
  
  
  RESULTS
  For elite suppressors, 10/18 had BED-CEIA values <0.8 normalized optical density units (OD-n) and these values did not change significantly over time. For patients receiving ART, 14/18 had BED-CEIA values that decreased over time, with a median decrease of 0.42 OD-n (range 0.10 to 0.63)/time point receiving ART. Three patterns of BED-CEIA values were observed during viral breakthrough: (1) values that increased then returned to pre-breakthrough values when viral suppression was re-established, (2) values that increased after viral breakthrough, and (3) values that did not change with viral breakthrough.
  
  
  CONCLUSIONS
  Viral suppression and viral breakthrough were associated with changes in BED-CEIA values, reflecting changes in the proportion of HIV-specific IgG. These changes can result in misclassification of patients with long-term HIV infection as recently infected using the BED-CEIA, thereby influencing a falsely high value for cross-sectional incidence estimates.
authors: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, Maryland, USA.
authors: Sarah K
authors: SK
authors: Wendel
authors: Caroline E
authors: CE
authors: Mullis
authors: Susan H
authors: SH
authors: Eshleman
authors: Joel N
authors: JN
authors: Blankson
authors: Richard D
authors: RD
authors: Moore
authors: Jeanne C
authors: JC
authors: Keruly
authors: Ron
authors: R
authors: Brookmeyer
authors: Thomas C
authors: TC
authors: Quinn
authors: Oliver
authors: O
authors: Laeyendecker
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000915:Antibody Affinity / Q000187:drug effects / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000145:classification / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D015483:HIV Antibodies