Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection

• DOI: 10.1126/scitranslmed.aad5752
• Publication Date: 2015-12-23T19:43:44Z
• Authors: Rebecca M. Lynch; Eli Boritz; Emily E. Coates; Adam DeZure; Patrick Madden; Pamela Costner; Mary E. Enama; Sarah Plummer; Lasonji Holman; Cynthia S. Hendel; Ingelise Gordon; Joseph Casazza; Michelle Conan-Ci...; Stephen A. Migueles; Randall Tressler; Robert T. Bailer; Adrian McDermott; Sandeep Narpala; Sijy O’Dell; Gideon Wolf; Jeffrey D. Lifson; Brandie A. Freemire; Robert J. Gorelick; Janardan P. Pandey; Sarumathi Mohan; Nicolas Chomont; Remi Fromentin; Tae-Wook Chun; Anthony S. Fauci; Richard M. Schwartz; Richard A. Koup; Daniel C. Douek; Zonghui Hu; Edmund Capparelli; Barney S. Graham; John R. Mascola; Julie E. Ledgerwood
• Keywords: Adult; Aged, 80 and over; CD4-Positive T-Lymphocytes; 0301 basic medicine; Adolescent; HIV Infections; HIV Antibodies; Middle Aged; Viral Load; Antibodies, Neutralizing; 3. Good health; Kinetics; Young Adult; 03 medical and health sciences; Antiretroviral Therapy, Highly Active; Chronic Disease; HIV-1; Humans; Aged

Passive immunization with HIV-1-neutralizing monoclonal antibodies (mAbs) is being considered for prevention and treatment of HIV-1 infection. As therapeutic agents, mAbs could be used to suppress active virus replication, maintain suppression induced by antiretroviral therapy (ART), and/or decrease the size persistent reservoir. We assessed impact VRC01, a potent human mAb targeting CD4 binding site, on ART-treated untreated HIV-1-infected subjects. Among six individuals undetectable plasma viremia, two infusions VRC01 did not reduce peripheral blood cell-associated reservoir measured 4 weeks after second infusion. In contrast, eight ART-untreated, viremic subjects infused single dose experienced 1.1 1.8 log10 reduction in viremia. The minimal responses were found have predominantly VRC01-resistant before treatment. Notably, load <1000 copies/ml demonstrated levels over 20 days until declined. remaining four baseline loads between 3000 30,000 copies, viremia was only partially suppressed infusion, we observed strong selection pressure outgrowth less neutralization-sensitive viruses. summary, infusion significantly decreased preferentially strains. These data demonstrate virological effect this neutralizing antibody highlight need combination strategies suppression.