Neutralizing antibody VRC01 failed to select for HIV-1 mutations upon viral rebound
Evan M. Cale, … , Morgane Rolland, on behalf of the RV397 Study Group
Evan M. Cale, … , Morgane Rolland, on behalf of the RV397 Study Group
Published March 17, 2020
Citation Information: J Clin Invest. 2020;130(6):3299-3304. https://doi.org/10.1172/JCI134395.
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Concise Communication AIDS/HIV

Neutralizing antibody VRC01 failed to select for HIV-1 mutations upon viral rebound

Abstract

Infusion of the broadly neutralizing antibody VRC01 has been evaluated in individuals chronically infected with HIV-1. Here, we studied how VRC01 infusions affected viral rebound after cessation of antiretroviral therapy (ART) in 18 acutely treated and durably suppressed individuals. Viral rebound occurred in all individuals, yet VRC01 infusions modestly delayed rebound and participants who showed a faster decay of VRC01 in serum rebounded more rapidly. Participants with strains most sensitive to VRC01 or with VRC01 epitope motifs similar to known VRC01-susceptible strains rebounded later. Upon rebound, HIV-1 sequences were indistinguishable from those sampled at diagnosis. Across the cohort, participant-derived Env showed different sensitivity to VRC01 neutralization (including 2 resistant viruses), yet neutralization sensitivity was similar at diagnosis and after rebound, indicating the lack of selection for VRC01 resistance during treatment interruption. Our results showed that viremia rebounded despite the absence of HIV-1 adaptation to VRC01 and an average VRC01 trough of 221 μg/mL. Although VRC01 levels were insufficient to prevent a resurgent infection, knowledge that they did not mediate Env mutations in acute-like viruses is relevant for antibody-based strategies in acute infection.

Authors

Evan M. Cale, Hongjun Bai, Meera Bose, Michael A. Messina, Donn J. Colby, Eric Sanders-Buell, Bethany Dearlove, Yifan Li, Emily Engeman, Daniel Silas, Anne Marie O’Sullivan, Brendan Mann, Suteeraporn Pinyakorn, Jintana Intasan, Khunthalee Benjapornpong, Carlo Sacdalan, Eugène Kroon, Nittaya Phanuphak, Robert Gramzinski, Sandhya Vasan, Merlin L. Robb, Nelson L. Michael, Rebecca M. Lynch, Robert T. Bailer, Amélie Pagliuzza, Nicolas Chomont, Amarendra Pegu, Nicole A. Doria-Rose, Lydie Trautmann, Trevor A. Crowell, John R. Mascola, Jintanat Ananworanich, Sodsai Tovanabutra, Morgane Rolland, on behalf of the RV397 Study Group

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Figure 3

Relationship between VRC01 decay rate, neutralization sensitivity, and time to rebound in participants who received VRC01 infusions.

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Relationship between VRC01 decay rate, neutralization sensitivity, and t...
Time to viral rebound was associated with the decay rate of VRC01 in serum after the first infusion (based on measurements on days 7, 14, and 21) (A). Time to viral rebound was also associated with the sensitivity to VRC01 using IC50/IC80 values corresponding to sequences sampled in acute infection (B and C) and to the VRC01 epitope distances (predicted from each participant’s sequences) (E and F). Predicted epitope distances were also correlated with the time to viral rebound (D). The time to rebound is the number of days between treatment cessation and an HIV-1 RNA test of 20 or more copies/mL. All 13 participants who received VRC01 infusions are represented; an asterisk before the participant ID indicates non-CRF01_AE infections.