SMAC Mimetic Plus Triple-Combination Bispecific HIVxCD3 Retargeting Molecules in SHIV.C.CH505-Infected, Antiretroviral Therapy-Suppressed Rhesus Macaques

Author:

Dashti Amir1ORCID,Waller Chevaughn1,Mavigner Maud12ORCID,Schoof Nils1,Bar Katharine J.3,Shaw George M.3,Vanderford Thomas H.4,Liang Shan4,Lifson Jeffrey D.5,Dunham Richard M.678ORCID,Ferrari Guido9,Tuyishime Marina9ORCID,Lam Chia-Ying K.10,Nordstrom Jeffrey L.10,Margolis David M.78,Silvestri Guido41112,Chahroudi Ann142ORCID

Affiliation:

1. Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA

2. Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA

3. Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

4. Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA

5. AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA

6. HIV Drug Discovery, ViiV Healthcare, Research Triangle Park, North Carolina, USA

7. UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

8. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

9. Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA

10. MacroGenics, Inc., Rockville, Maryland, USA

11. Emory Vaccine Center, Emory University, Atlanta, Georgia, USA

12. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA

Abstract

The most significant barrier to an HIV-1 cure is the existence of the latently infected viral reservoir that gives rise to rebound viremia upon cessation of ART. Here, we tested a novel combination approach of latency reversal with AZD5582 and clearance with bispecific HIVxCD3 DART molecules in SHIV.C.CH505-infected, ART-suppressed rhesus macaques. We demonstrate that the DART molecules were not capable of clearing infected cells in vivo , attributed to the lack of quantifiable latency reversal in this model with low levels of persistent SHIV DNA prior to intervention as well as DART molecule immunogenicity.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference58 articles.

1. . 2019. UNAIDS data 2019. Joint United Nations Program on HIV/AIDS, Geneva, Switzerland.

2. Getting the “Kill” into “Shock and Kill”: Strategies to Eliminate Latent HIV

3. Curing HIV: Seeking to Target and Clear Persistent Infection

4. Reference deleted.

5. Reference deleted.

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