32nd International Dynamics & Evolution of Human Viruses

IMPACT OF HIV-1 VIRAL LOAD BLIPS ON HIV-1 BINDING ANTIBODY LEVEL DYNAMICS

Not scheduled

20m

Abbaye de Royaumont, Asnières-sur-Oise, France

Oral Within-host dynamics & adaptation

Speaker

Dr Baptiste Elie (Institute of Medical Virology, University of Zurich & Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich (USZ), Zurich, Switzerland)

Description

Viral "blips" are single timepoint episodes with detectable plasma HIV-1 RNA preceded and followed by undetectable viremia in individuals on antiretroviral therapy (ART). Despite their common occurrence, the origin, biological implications, and clinical consequences of viral blips for people with HIV (PWH) remain unclear. Proposed explanations include intermittent viral release from latent reservoirs, assay variability, or ongoing viral replication. This study investigates whether viral blips are temporally linked to activation of the adaptive immune response.

We analyzed plasma samples from 117 participants in the Zurich Primary HIV Infection (ZPHI) study (PMID: 38399706), all of whom initiated ART within 120 days of infection (mean: 52 days, inter-quartile range (IQR): 28-64) and were followed for over 4 years. Using a binding antibody multiplex assay (BAMA), we measured IgG1, IgG3, and IgA to 15 HIV-1 antigens at 8 time points, including an initial off-ART sample. Viral loads were measured every 81 days on average (IQR: 74-86).

Among the 117 participants, 50 had no detectable viremia post-ART initiation, 27 experienced at least one viral blip (mean: 1.6, IQR: 1-2), and 40 had persistent viral relapses. Statistical modeling, accounting for antibody waning after ART-mediated suppression and viral load, showed that viral blips were significantly associated with increased antibody binding to some HIV-1 antigens. Notably, IgG1 binding to gp120 and p17 increased by 2.0 (95% credible interval (CrI): 1.7-2.2) and 1.9 (95% CrI: 1.6-2.1) times, respectively, following a blip. Interestingly, the boosting effect on antibody levels was seen at very low viral loads (<50 RNA copies/mL), which are considered clinically irrelevant. We further compared this response to viremic episodes in PWH and low-level viremia or patients who underwent analytic treatment interruptions.

Our findings suggest that viral blips, even when viral load is low, lead to temporary reactivation of antibody responses.