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Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption.
Bar, Katharine J; Sneller, Michael C; Harrison, Linda J; Justement, J Shawn; Overton, Edgar T; Petrone, Mary E; Salantes, D Brenda; Seamon, Catherine A; Scheinfeld, Benjamin; Kwan, Richard W; Learn, Gerald H; Proschan, Michael A; Kreider, Edward F; Blazkova, Jana; Bardsley, Mark; Refsland, Eric W; Messer, Michael; Clarridge, Katherine E; Tustin, Nancy B; Madden, Patrick J; Oden, KaSaundra; O'Dell, Sijy J; Jarocki, Bernadette; Shiakolas, Andrea R; Tressler, Randall L; Doria-Rose, Nicole A; Bailer, Robert T; Ledgerwood, Julie E; Capparelli, Edmund V; Lynch, Rebecca M; Graham, Barney S; Moir, Susan; Koup, Richard A; Mascola, John R; Hoxie, James A; Fauci, Anthony S; Tebas, Pablo; Chun, Tae-Wook.
Afiliação
  • Bar KJ; 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 Bra
  • Sneller MC; 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 Bra
  • Harrison LJ; 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 Bra
  • Justement JS; 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 Bra
  • Overton ET; 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 Bra
  • Petrone ME; 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 Bra
  • Salantes DB; 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 Bra
  • Seamon CA; 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 Bra
  • Scheinfeld B; 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 Bra
  • Kwan RW; 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 Bra
  • Learn GH; 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 Bra
  • Proschan MA; 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 Bra
  • Kreider EF; 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 Bra
  • Blazkova J; 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 Bra
  • Bardsley M; 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 Bra
  • Refsland EW; 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 Bra
  • Messer M; 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 Bra
  • Clarridge KE; 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 Bra
  • Tustin NB; 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 Bra
  • Madden PJ; 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 Bra
  • Oden K; 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 Bra
  • O'Dell SJ; 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 Bra
  • Jarocki B; 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 Bra
  • Shiakolas AR; 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 Bra
  • Tressler RL; 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 Bra
  • Doria-Rose NA; 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 Bra
  • Bailer RT; 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 Bra
  • Ledgerwood JE; 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 Bra
  • Capparelli EV; 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 Bra
  • Lynch RM; 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 Bra
  • Graham BS; 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 Bra
  • Moir S; 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 Bra
  • Koup RA; 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 Bra
  • Mascola JR; 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 Bra
  • Hoxie JA; 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 Bra
  • Fauci AS; 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 Bra
  • Tebas P; 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 Bra
  • Chun TW; 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 Bra
N Engl J Med ; 375(21): 2037-2050, 2016 11 24.
Article em En | MEDLINE | ID: mdl-27959728
ABSTRACT

BACKGROUND:

The 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).

METHODS:

We 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.

RESULTS:

A 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.

CONCLUSIONS:

VRC01 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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Viremia / Infecções por HIV / HIV / Anticorpos Neutralizantes / Anticorpos Monoclonais Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
Imprimir
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PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Viremia / Infecções por HIV / HIV / Anticorpos Neutralizantes / Anticorpos Monoclonais Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2016 Tipo de documento: Article