TY - JOUR
T1 - Neutralizing antibody VRC01 failed to select for HIV-1 mutations upon viral rebound
AU - Cale, Evan M.
AU - Bai, Hongjun
AU - Bose, Meera
AU - Messina, Michael A.
AU - Colby, Donn J.
AU - Sanders-Buell, Eric
AU - Dearlove, Bethany
AU - Li, Yifan
AU - Engeman, Emily
AU - Silas, Daniel
AU - O'Sullivan, Anne Marie
AU - Mann, Brendan
AU - Pinyakorn, Suteeraporn
AU - Intasan, Jintana
AU - Benjapornpong, Khunthalee
AU - Sacdalan, Carlo
AU - Kroon, Eugène
AU - Phanuphak, Nittaya
AU - Gramzinski, Robert
AU - Vasan, Sandhya
AU - Robb, Merlin L.
AU - Michael, Nelson L.
AU - Lynch, Rebecca M.
AU - Bailer, Robert T.
AU - Pagliuzza, Amélie
AU - Chomont, Nicolas
AU - Pegu, Amarendra
AU - Doria-Rose, Nicole A.
AU - Trautmann, Lydie
AU - Crowell, Trevor A.
AU - Mascola, John R.
AU - Ananworanich, Jintanat
AU - Tovanabutra, Sodsai
AU - Rolland, Morgane
N1 - Funding Information:
We are indebted to the RV397 participants and study team (Supplemental Acknowledgments). The authors thank Diane Bolton, Paul Edlefsen, and Daniel Reeves. This work was supported by a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the US Department of the Army (W81XWH-18-2-0174). The views expressed are those of the authors and should not be construed to represent the positions of the US Army, the Department of Defense, or the Department of Health and Human Services.
Publisher Copyright:
© 2020 Cale et al.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
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U2 - 10.1172/JCI134395
DO - 10.1172/JCI134395
M3 - Article
C2 - 32182219
AN - SCOPUS:85085712871
SN - 0021-9738
VL - 130
SP - 3299
EP - 3304
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 6
ER -