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Viral Rebound Kinetics Correlate with Distinct HIV Antibody Features.

Yannic C Bartsch1, Carolin Loos1,2, Evan Rossignol1

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Mbio
|March 10, 2021
PubMed
Summary

Antibody features like Fc functionality and Fc glycosylation predict viral rebound timing after stopping antiretroviral therapy (ART) in HIV patients. Distinct antibody profiles separated early and delayed viral rebounders, offering new biomarkers for HIV disease activity.

Keywords:
antibody functionglycosylationhuman immunodeficiency virusimmune activationviral reservoir

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Area of Science:

  • Immunology
  • Virology
  • HIV Research

Background:

  • Plasma viremia recurrence is common after antiretroviral therapy (ART) interruption in HIV-infected individuals.
  • Viral rebound kinetics vary significantly, with limited predictive power from standard markers like CD4 counts.
  • Antibody Fc functionality and glycosylation are emerging as sensitive disease activity surrogates.

Purpose of the Study:

  • To analyze HIV-specific antibody quantity and quality, including Fc-mediated functions and Fc glycosylation, before an analytical ART interruption (ATI).
  • To determine if antibody features can predict the timing of viral rebound after ART cessation.
  • To correlate antibody profiles with inflammatory cytokines and viral reservoir activity.

Main Methods:

  • Analysis of HIV-specific antibody quantity, FcγR binding, Fc glycosylation, cytokine profiles, and cellular HIV DNA/RNA in 23 ART-suppressed individuals.
  • Participants underwent an analytical ART interruption (ATI).
  • Correlation of antibody features with early (≤4 weeks) versus delayed (>4 weeks) viral rebound.

Main Results:

  • Distinct antibody functional properties and Fc glycan signatures differentiated early and delayed viral rebounders.
  • Early rebounders showed higher levels of HIV-specific IgGs with inflammatory Fc glycans.
  • Delayed rebounders exhibited an enrichment of highly functional antibodies and enhanced antibody-mediated NK cell activation.

Conclusions:

  • Antibody features, including Fc functionality and Fc glycosylation, serve as sensitive indicators of HIV disease activity.
  • These antibody characteristics can predict viral rebound kinetics following ART interruption.
  • Antibody profiling could be valuable for future HIV eradication and ATI studies.