- June 2, 2026
Topic/Product:
HIV, Inflammation, Inflammation Panel 250
Disease Area:
Infectious Disease
Sample Type:
Plasma
Abstract
Broadly neutralizing antibodies (bNAbs) have been associated with enhancement of HIV-specific T or B cell responses and sustained partial control of HIV replication in some people with HIV (PWH). The mechanisms through which bNAbs may potentiate host immunity in this context are not known. We previously reported the outcomes of a clinical trial in which ten PWH on antiretroviral therapy (ART) received a combination of immunotherapies including two bNAbs administered immediately preceding an analytic treatment interruption (ATI). After bNAb levels waned, seven participants exhibited varying degrees of post-intervention control of HIV linked to a robust expansion of activated CD8+ T cells in response to rebounding virus. To investigate the role of the bNAbs in enhancing endogenous immune responses, we looked for evidence of HIV-specific or broader immune activation during the period after ART was paused and prior to rebound when bNAbs were controlling HIV replication. At a timepoint early post-ART interruption and at least one month before virus emerged in plasma, we detected an increase in levels of plasma inflammatory proteins as well as phenotypic and transcriptional activation of innate and adaptive immune cells. Compared to non-controllers, post-intervention controllers demonstrated unique transcriptional activation patterns as well as differential longitudinal plasma inflammatory protein trends. No enhancement of HIV-specific T cell or antibody responses was observed in this window. This study identifies activated cell types and inflammatory pathways that are recruited early during bNAb-mediated HIV suppression and that may play a role in potentiating long-lasting HIV immune control after bNAb therapy.
Authors and Affiliations
Julia A. Wagner1, Demi A. Sandel1, Ravi K. Patel2, George W. Gruenhagen1, Rafael Tibúrcio1, Shayleen S. Singh1, Kaiti Schwartz1, Michela Traglia3, Pamela Milani4,5, Clara Di Germanio4,5, Shlomi Ilan6, Thomas Dalhuisen1, Rebecca Hoh1, Meghann C. Williams1, Michiko Shimoda1, Reuben Thomas3, Boris Juelg6, Matthew H. Spitzer7,8,9,10, Amelia N. Deitchman11, Michael P. Busch4,5, Gabriela K. Fragiadakis1,2, Peter W. Hunt1, Michael J. Peluso1, Steven G. Deeks1, Rachel L. Rutishauser1*
1 Department of Medicine, University of California, San Francisco, San Francisco, CA, USA
2 UCSF CoLabs Initiative, University of California, San Francisco, San Francisco, CA, USA
3 The Gladstone Institutes, San Francisco, CA, USA
4 Vitalant Research Institute, San Francisco, CA, USA
5 Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, USA
6 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA
7 Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, San Francisco, CA, USA.
8 Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
9 Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
10 Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA, USA.
11 Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, USA