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AZD5582 plus SIV-specific antibodies reduce lymph node viral reservoirs in antiretroviral therapy-suppressed macaques.

Publication ,  Journal Article
Dashti, A; Sukkestad, S; Horner, AM; Neja, M; Siddiqi, Z; Waller, C; Goldy, J; Monroe, D; Lin, A; Schoof, N; Singh, V; Mavigner, M; King, HAD ...
Published in: Nat Med
October 2023

The main barrier to HIV cure is a persistent reservoir of latently infected CD4+ T cells harboring replication-competent provirus that fuels rebound viremia upon antiretroviral therapy (ART) interruption. A leading approach to target this reservoir involves agents that reactivate latent HIV proviruses followed by direct clearance of cells expressing induced viral antigens by immune effector cells and immunotherapeutics. We previously showed that AZD5582, an antagonist of inhibitor of apoptosis proteins and mimetic of the second mitochondrial-derived activator of caspases (IAPi/SMACm), induces systemic reversal of HIV/SIV latency but with no reduction in size of the viral reservoir. In this study, we investigated the effects of AZD5582 in combination with four SIV Env-specific Rhesus monoclonal antibodies (RhmAbs) ± N-803 (an IL-15 superagonist) in SIV-infected, ART-suppressed rhesus macaques. Here we confirm the efficacy of AZD5582 in inducing SIV reactivation, demonstrate enhancement of latency reversal when AZD5582 is used in combination with N-803 and show a reduction in total and replication-competent SIV-DNA in lymph-node-derived CD4+ T cells in macaques treated with AZD5582 + RhmAbs. Further exploration of this therapeutic approach may contribute to the goal of achieving an HIV cure.

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Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

October 2023

Volume

29

Issue

10

Start / End Page

2535 / 2546

Location

United States

Related Subject Headings

  • Virus Replication
  • Virus Latency
  • Viral Load
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Macaca mulatta
  • Lymph Nodes
  • Immunology
  • HIV-1
 

Citation

APA
Chicago
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Dashti, A., Sukkestad, S., Horner, A. M., Neja, M., Siddiqi, Z., Waller, C., … Chahroudi, A. (2023). AZD5582 plus SIV-specific antibodies reduce lymph node viral reservoirs in antiretroviral therapy-suppressed macaques. Nat Med, 29(10), 2535–2546. https://doi.org/10.1038/s41591-023-02570-7
Dashti, Amir, Sophia Sukkestad, Anna M. Horner, Margaret Neja, Zain Siddiqi, Chevaughn Waller, Jordan Goldy, et al. “AZD5582 plus SIV-specific antibodies reduce lymph node viral reservoirs in antiretroviral therapy-suppressed macaques.Nat Med 29, no. 10 (October 2023): 2535–46. https://doi.org/10.1038/s41591-023-02570-7.
Dashti A, Sukkestad S, Horner AM, Neja M, Siddiqi Z, Waller C, et al. AZD5582 plus SIV-specific antibodies reduce lymph node viral reservoirs in antiretroviral therapy-suppressed macaques. Nat Med. 2023 Oct;29(10):2535–46.
Dashti, Amir, et al. “AZD5582 plus SIV-specific antibodies reduce lymph node viral reservoirs in antiretroviral therapy-suppressed macaques.Nat Med, vol. 29, no. 10, Oct. 2023, pp. 2535–46. Pubmed, doi:10.1038/s41591-023-02570-7.
Dashti A, Sukkestad S, Horner AM, Neja M, Siddiqi Z, Waller C, Goldy J, Monroe D, Lin A, Schoof N, Singh V, Mavigner M, Lifson JD, Deleage C, Tuyishime M, Falcinelli SD, King HAD, Ke R, Mason RD, Archin NM, Dunham RM, Safrit JT, Jean S, Perelson AS, Margolis DM, Ferrari G, Roederer M, Silvestri G, Chahroudi A. AZD5582 plus SIV-specific antibodies reduce lymph node viral reservoirs in antiretroviral therapy-suppressed macaques. Nat Med. 2023 Oct;29(10):2535–2546.

Published In

Nat Med

DOI

EISSN

1546-170X

Publication Date

October 2023

Volume

29

Issue

10

Start / End Page

2535 / 2546

Location

United States

Related Subject Headings

  • Virus Replication
  • Virus Latency
  • Viral Load
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Macaca mulatta
  • Lymph Nodes
  • Immunology
  • HIV-1