HIV Antibody Profiles in HIV Controllers and Persons With Treatment-Induced Viral Suppression

Front Immunol. 2021 Aug 26:12:740395. doi: 10.3389/fimmu.2021.740395. eCollection 2021.


Introduction: Low HIV viral load is associated with delayed disease progression and reduced HIV transmission. HIV controllers suppress viral load to low levels in the absence of antiretroviral treatment (ART). We used an antibody profiling system, VirScan, to compare antibody reactivity and specificity in HIV controllers, non-controllers with treatment-induced viral suppression, and viremic non-controllers.

Methods: The VirScan library contains 3,384 phage-displayed peptides spanning the HIV proteome. Antibody reactivity to these peptides was measured in plasma from a Discovery Cohort that included 13 elite controllers, 27 viremic controllers, 12 viremic non-controllers, and 21 non-controllers who were virally suppressed on ART. Antibody reactivity to selected peptides was also assessed in an independent cohort of 29 elite controllers and 37 non-controllers who were virally suppressed on ART (Validation Cohort) and in a longitudinal cohort of non-controllers.

Results: In the Discovery Cohort, 62 peptides were preferentially targeted in HIV controllers compared to non-controllers who were virally suppressed on ART. These specificities were not significantly different when comparing controllers versus viremic non-controllers. Aggregate reactivity to these peptides was also high in elite controllers from the independent Validation Cohort. The 62 peptides formed seven clusters of homologous epitopes in env, gag, integrase, and vpu. Reactivity to one of these clusters located in gag p17 was inversely correlated with viral load set point in an independent cohort of non-controllers.

Conclusions: Antibody reactivity was low in non-controllers suppressed on ART, but remained high in viremic controllers despite viral suppression. Antibodies in controllers and viremic non-controllers were directed against epitopes in diverse HIV proteins; higher reactivity against p17 peptides was associated with lower viral load set point. Further studies are needed to determine if these antibodies play a role in regulation of HIV viral load.

Keywords: HIV control; VirScan; antibody profiling; phage display; viral load set point.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • Epitope Mapping
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • HIV Antibodies / immunology*
  • HIV Antigens / genetics
  • HIV Antigens / immunology
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Non-Progressors*
  • HIV-1 / physiology*
  • Humans
  • Male
  • Peptide Library
  • Viral Load
  • Young Adult
  • gag Gene Products, Human Immunodeficiency Virus / genetics
  • gag Gene Products, Human Immunodeficiency Virus / immunology


  • Anti-Retroviral Agents
  • Epitopes
  • HIV Antibodies
  • HIV Antigens
  • Peptide Library
  • gag Gene Products, Human Immunodeficiency Virus
  • p17 protein, Human Immunodeficiency Virus Type 1