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Broadly neutralizing antibody treatment maintained HIV suppression in children with favorable reservoir characteristics in Botswana.
Shapiro, Roger L; Ajibola, Gbolahan; Maswabi, Kenneth; Hughes, Michael; Nelson, Bryan S; Niesar, Aischa; Pretorius Holme, Molly; Powis, Kathleen M; Sakoi, Maureen; Batlang, Oganne; Moyo, Sikhulile; Mohammed, Terence; Maphorisa, Comfort; Bennett, Kara; Hu, Zixin; Giguel, Francoise; Reeves, Jacqueline D; Reeves, Michael A; Gao, Ce; Yu, Xu; Ackerman, Margaret E; McDermott, Adrian; Cooper, Marlene; Caskey, Marina; Gama, Lucio; Jean-Philippe, Patrick; Yin, Dwight E; Capparelli, Edmund V; Lockman, Shahin; Makhema, Joseph; Kuritzkes, Daniel R; Lichterfeld, Mathias.
Afiliación
  • Shapiro RL; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
  • Ajibola G; Botswana Harvard Health Partnership, Gaborone, Botswana.
  • Maswabi K; Botswana Harvard Health Partnership, Gaborone, Botswana.
  • Hughes M; Botswana Harvard Health Partnership, Gaborone, Botswana.
  • Nelson BS; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
  • Niesar A; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
  • Pretorius Holme M; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Powis KM; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
  • Sakoi M; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
  • Batlang O; Botswana Harvard Health Partnership, Gaborone, Botswana.
  • Moyo S; Departments of Internal Medicine and Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Mohammed T; Botswana Harvard Health Partnership, Gaborone, Botswana.
  • Maphorisa C; Botswana Harvard Health Partnership, Gaborone, Botswana.
  • Bennett K; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
  • Hu Z; Botswana Harvard Health Partnership, Gaborone, Botswana.
  • Giguel F; Botswana Harvard Health Partnership, Gaborone, Botswana.
  • Reeves JD; Botswana Harvard Health Partnership, Gaborone, Botswana.
  • Reeves MA; Bennett Statistical Consulting Inc., Ballston Lake, NY 12019, USA.
  • Gao C; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Yu X; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Ackerman ME; Labcorp-Monogram Biosciences Inc., South San Francisco, CA 94080, USA.
  • McDermott A; Labcorp-Monogram Biosciences Inc., South San Francisco, CA 94080, USA.
  • Cooper M; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Caskey M; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Gama L; Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
  • Jean-Philippe P; Vaccine Research Center, Bethesda, MD 20892, USA.
  • Yin DE; Frontier Science & Technology Research Foundation Inc., Amherst, NY 14226, USA.
  • Capparelli EV; Rockefeller University, New York, NY 10065, USA.
  • Lockman S; Vaccine Research Center, Bethesda, MD 20892, USA.
  • Makhema J; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA.
  • Kuritzkes DR; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20892, USA.
  • Lichterfeld M; Department of Pediatrics, University of California San Diego, La Jolla, CA 92037, USA.
Sci Transl Med ; 15(703): eadh0004, 2023 07 05.
Article en En | MEDLINE | ID: mdl-37406137
Broadly neutralizing antibodies (bNAbs) may provide an alternative to standard antiretroviral treatment (ART) for controlling HIV-1 replication and may have immunotherapeutic effects against HIV-1 reservoirs. We conducted a prospective clinical trial with two HIV-1 bNAbs (VRC01LS and 10-1074) in children (n = 25) who had previously initiated small-molecule ART treatment before 7 days of age and who continued treatment for at least 96 weeks. Both bNAbs were dosed intravenously every 4 weeks, overlapping with ART for at least 8 weeks and then continued for up to 24 weeks or until detectable viremia of HIV-1 RNA rose above 400 copies per milliliter in the absence of ART. Eleven (44%) children maintained HIV-1 RNA below 400 copies per milliliter through 24 weeks of bNAb-only treatment; 14 (56%) had detectable viremia above 400 copies per milliliter at a median of 4 weeks. Archived HIV-1 provirus susceptible to 10-1074, lower birth HIV-1 DNA reservoir in peripheral blood mononuclear cells, sustained viral suppression throughout early life, and combined negative qualitative HIV-1 DNA polymerase chain reaction and negative HIV-1 serology at entry were associated with maintaining suppression on bNAbs alone. This proof-of-concept study suggests that bNAbs may represent a promising treatment modality for infants and children living with HIV-1. Future studies using newer bNAb combinations with greater breadth and potency are warranted.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / VIH-1 Tipo de estudio: Clinical_trials / Observational_studies / Qualitative_research / Risk_factors_studies Límite: Child / Humans País/Región como asunto: Africa Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / VIH-1 Tipo de estudio: Clinical_trials / Observational_studies / Qualitative_research / Risk_factors_studies Límite: Child / Humans País/Región como asunto: Africa Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos