Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques-Reference-Cited by-同舟云学术

Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques

Published:2024-03-08 Issue:6687 Volume:383 Page:1104-1111
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Lim So-Yon¹^ORCID,Lee Jina¹^ORCID,Osuna Christa E.¹^ORCID,Vikhe Pratik¹^ORCID,Schalk Dane R.²^ORCID,Chen Elsa¹,Fray Emily³^ORCID,Kumar Mithra³^ORCID,Schultz-Darken Nancy²^ORCID,Rakasz Eva²^ORCID,Capuano Saverio²,Ladd Ruby A²^ORCID,Gil Hwi Min²^ORCID,Evans David T.²^ORCID,Jeng Emily K.⁴,Seaman Michael¹^ORCID,Martin Malcolm⁵^ORCID,Van Dorp Christiaan⁶^ORCID,Perelson Alan S.⁶⁷^ORCID,Wong Hing C.⁴,Siliciano Janet D.³^ORCID,Siliciano Robert³⁸^ORCID,Safrit Jeffrey T.⁹,Nixon Douglas F.¹⁰^ORCID,Soon-Shiong Patrick⁹^ORCID,Nussenzweig Michel¹¹¹²^ORCID,Whitney James B.¹¹³^ORCID

Affiliation:

1. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

2. Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA.

3. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

4. Altor Biosciences, Miramar, FL 33027, USA.

5. Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

6. Los Alamos National Laboratory, Los Alamos, NM 87545, USA.

7. Santa Fe Institute, Santa Fe, NM 87501, USA.

8. Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

9. ImmunityBio, Culver City, CA 90232, USA.

10. Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA.

11. Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.

12. Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.

13. Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.

Abstract

The eradication of the viral reservoir represents the major obstacle to the development of a clinical cure for established HIV-1 infection. Here, we demonstrate that the administration of N-803 (brand name Anktiva) and broadly neutralizing antibodies (bNAbs) results in sustained viral control after discontinuation of antiretroviral therapy (ART) in simian-human AD8 (SHIV-AD8)–infected, ART-suppressed rhesus macaques. N-803+bNAbs treatment induced immune activation and transient viremia but only limited reductions in the SHIV reservoir. Upon ART discontinuation, viral rebound occurred in all animals, which was followed by durable control in approximately 70% of all N-803+bNAb–treated macaques. Viral control was correlated with the reprogramming of CD8 + T cells by N-803+bNAb synergy. Thus, complete eradication of the replication-competent viral reservoir is likely not a prerequisite for the induction of sustained remission after discontinuation of ART.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adf7966

Reference48 articles.

1. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy

2. Quantifying Residual HIV-1 Replication in Patients Receiving Combination Antiretroviral Therapy

3. Re-emergence of HIV after stopping therapy

4. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection

5. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy

Cited by 4 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Biotech's role in advancing HIV vaccine development;Emerging Microbes & Infections;2024-08-12

2. Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion;PLOS Pathogens;2024-07-29

3. Immune checkpoint inhibition as a therapeutic strategy for HIV eradication: current insights and future directions;Current Opinion in HIV and AIDS;2024-05-15

4. Recent advances on anti-HIV chimeric antigen receptor-T-cell treatment to provide sustained HIV remission;Current Opinion in HIV and AIDS;2024-05-01