• Katharine J Bar, Michael C Sneller, Linda J Harrison, J Shawn Justement, Edgar T Overton, Mary E Petrone, D Brenda Salantes, Catherine A Seamon, Benjamin Scheinfeld, Richard W Kwan, Gerald H Learn, Michael A Proschan, Edward F Kreider, Jana Blazkova, Mark Bardsley, Eric W Refsland, Michael Messer, Katherine E Clarridge, Nancy B Tustin, Patrick J Madden, KaSaundra Oden, Sijy J O'Dell, Bernadette Jarocki, Andrea R Shiakolas, Randall L Tressler, Nicole A Doria-Rose, Robert T Bailer, Julie E Ledgerwood, Edmund V Capparelli, Rebecca M Lynch, Barney S Graham, Susan Moir, Richard A Koup, John R Mascola, James A Hoxie, Anthony S Fauci, Pablo Tebas, and Tae-Wook Chun.
• From the University of Pennsylvania (K.J.B., D.B.S., B.S., G.H.L., E.F.K., M.B., J.A.H., P.T.) and Children's Hospital of Philadelphia (N.B.T.) - both in Philadelphia; the Laboratory of Immunoregulation (M.C.S., J.S.J., M.E.P., J.B., E.W.R., K.E.C., S.M., A.S.F., T.-W.C.), Biostatistics Research Branch (M.A.P.), Vaccine Research Center (P.J.M., S.J.O., A.R.S., N.A.D.-R., R.T.B., J.E.L., R.M.L., B.S.G., R.A.K., J.R.M.), and Division of AIDS (R.L.T.), National Institute of Allergy and Infectious Diseases and National Institutes of Health (NIH), and the Critical Care Medicine Department, Clinical Center, NIH (C.A.S., R.W.K.), Bethesda, the AIDS Clinical Trials Group, Silver Spring (K.O.), and Columbus Technologies and Services, Greenbelt (R.L.T.) - all in Maryland; Harvard T.H. Chan School of Public Health, Boston (L.J.H.); the University of Alabama at Birmingham, Birmingham (E.T.O., M.M.); Frontier Science and Technology Research Foundation, Amherst, NY (B.J.); and the University of California, San Diego, La Jolla (E.V.C.).
• N. Engl. J. Med. 2016 Nov 24; 375 (21): 2037-2050.

BackgroundThe discovery of potent and broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) has made passive immunization a potential strategy for the prevention and treatment of HIV infection. We sought to determine whether passive administration of VRC01, a bNAb targeting the HIV CD4-binding site, can safely prevent or delay plasma viral rebound after the discontinuation of antiretroviral therapy (ART).MethodsWe conducted two open-label trials (AIDS Clinical Trials Group [ACTG] A5340 and National Institutes of Health [NIH] 15-I-0140) of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of VRC01 in persons with HIV infection who were undergoing interruption of ART.ResultsA total of 24 participants were enrolled, and one serious alcohol-related adverse event occurred. Viral rebound occurred despite plasma VRC01 concentrations greater than 50 μg per milliliter. The median time to rebound was 4 weeks in the A5340 trial and 5.6 weeks in the NIH trial. Study participants were more likely than historical controls to have viral suppression at week 4 (38% vs. 13%, P=0.04 by a two-sided Fisher's exact test in the A5340 trial; and 80% vs. 13%, P<0.001 by a two-sided Fisher's exact test in the NIH trial) but the difference was not significant at week 8. Analyses of virus populations before ART as well as before and after ART interruption showed that VRC01 exerted pressure on rebounding virus, resulting in restriction of recrudescent viruses and selection for preexisting and emerging antibody neutralization-resistant virus.ConclusionsVRC01 slightly delayed plasma viral rebound in the trial participants, as compared with historical controls, but it did not maintain viral suppression by week 8. In the small number of participants enrolled in these trials, no safety concerns were identified with passive immunization with a single bNAb (VRC01). (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTG A5340 and NIH 15-I-0140 ClinicalTrials.gov numbers, NCT02463227 and NCT02471326 .).

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