Drift of the HIV-1 Envelope Glycoprotein gp120 toward Increased Neutralization Resistance over the Course of the Epidemic: a Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies

Extending our previous analyses to the most recently described monoclonal broadly neutralizing antibodies (bNAbs), we con-firmed a drift of HIV-1 clade B variants over 2 decades toward higher resistance to bNAbs targeting almost all the identified gp120-neutralizing epitopes. In contrast, the sensitivity to bNAbs targeting the gp41 membrane-proximal external region re-mained stable, suggesting a selective pressure on gp120 preferentially. Despite this evolution, selected combinations of bNAbs remain capable of neutralizing efficiently most of the circulating variants. Despite the ability of HIV-1 to evade the antibody response,some HIV-1-infected individuals develop high titers of broadly neutralizing antibodies (bNAbs) (1–11). Since 2009, thanks to the development of single-cell-based antibody cloning techniques, a large number of monoclonal bNAbs with outstand-ing potencies have been isolated from such individuals (12–21). Most of them target a few major sites of vulnerability on HIV-