Presentation is loading. Please wait.

Presentation is loading. Please wait.

Ixazomib reduces HIV-1 reservoir size in a Casp8p41-dependent manner

Published byHeather Summers Modified over 6 years ago

Similar presentations

Presentation on theme: "Ixazomib reduces HIV-1 reservoir size in a Casp8p41-dependent manner"— Presentation transcript:

1 Ixazomib reduces HIV-1 reservoir size in a Casp8p41-dependent manner
Nathan W Cummins, MD Assistant Professor of Medicine, Consultant in Infectious Diseases, Chair of Infectious Diseases Research, Mayo Clinic College of Medicine and Science Rochester, MN USA

2 Disclosures Research funding from Takeda Pharmaceuticals
Off-label usage – Ixazomib – FDA IND

3 Casp8p41/Bcl2 complex is polyubiquinated for proteasomal degradation.
HIV-1 protease cleaves procaspase 8 Casp8p41, which is expressed exclusively in infected cells, and is bound and inactivated by Bcl2 Casp8p41/Bcl2 complex is polyubiquinated for proteasomal degradation. Proteasome inhibitors, including ixazomib, increase Casp8p41 expression. Proteasome inhibitors independently induce HIV-1 reactivation in an NFkB dependent manner Proteasome inhibitors induce preferential apoptosis in HIV-1 infected cells versus uninfected cells. Treatment of ex vivo CD4 T cells from ART-suppressed patients with ixazomib significantly reduces total and integrated HIV-1 DNA.

4

5 Phase 1b/2a, single center, dose escalation cohort clinical trial of ixazomib in ART-suppressed patients NCT IND 11 of 17 participants enrolled No serious AEs in 1mg, 2mg (completed) or 3mg (ongoing) cohorts to date HIV-1 reservoir measurements in peripheral CD4 T cells will be reported at a later date

6 Acknowledgments Andrew D. Badley Clinical Trial Team
Badley HIV Immunology Lab, Mayo Clinic Sekar Natesampillai Zilin Nie Rahul Sampath Gary Bren Amy Sainski Mayo Clinic Collaborators Scott Kaufmann David J. Katzmann Eric Polley External Collaborators Jason V. Baker Keith Henry Marilia Pinzone Una O’Doherty Clinical Trial Team Stacey A. Rizza Aaron J. Tande Maryam Mahmood Shaji Kumar John Zeuli Christina Rivera James Allen DSMB Jennifer Whitaker Zelalem Temesgen Vincent Rajkumar

Download ppt "Ixazomib reduces HIV-1 reservoir size in a Casp8p41-dependent manner"

Similar presentations

Effect of intensification of long-term highly active antiretroviral therapy (HAART) with raltegravir on proviral HIV-1 DNA in blood and gut associated.

Effect of intensification of long-term highly active antiretroviral therapy (HAART) with raltegravir on proviral HIV-1 DNA in blood and gut associated.
Slide #1 HIV Entry Inhibitors Trip Gulick, MD, MPH Director, Cornell HIV Clinical Trials Unit Associate Professor of Medicine Weill Medical College of.

Slide #1 HIV Entry Inhibitors Trip Gulick, MD, MPH Director, Cornell HIV Clinical Trials Unit Associate Professor of Medicine Weill Medical College of.
Future Trials of Hepatitis C Therapy in the HIV Co-infected Stephen D. Shafran, MD, FRCPC, FACP Department of Medicine, Division of Infectious Diseases.

Future Trials of Hepatitis C Therapy in the HIV Co-infected Stephen D. Shafran, MD, FRCPC, FACP Department of Medicine, Division of Infectious Diseases.
Www.aids2014.org The HDAC inhibitor romidepsin is safe and effectively reverses HIV-1 latency in vivo as measured by standard clinical assays Ole Schmeltz.

The HDAC inhibitor romidepsin is safe and effectively reverses HIV-1 latency in vivo as measured by standard clinical assays Ole Schmeltz.
Gag-positive reservoir cells can be identified by a new technique and can be cleared by CTL ? Una O’Doherty June 29, 2013.

Gag-positive reservoir cells can be identified by a new technique and can be cleared by CTL ? Una O’Doherty June 29, 2013.
Inhibition of Poly (ADP-Ribose) Polymerase (PARP) by ABT-888 in Patients With Advanced Malignancies: Results of a Phase 0 Trial Shivaani Kummar, MD National.

Inhibition of Poly (ADP-Ribose) Polymerase (PARP) by ABT-888 in Patients With Advanced Malignancies: Results of a Phase 0 Trial Shivaani Kummar, MD National.
Richardson PG et al. Proc ASH 2013;Abstract 535.

Richardson PG et al. Proc ASH 2013;Abstract 535.
David M. Margolis, MD Professor of Medicine Towards an HIV cure: medical, social and ethical challenges in research and testing.

David M. Margolis, MD Professor of Medicine Towards an HIV cure: medical, social and ethical challenges in research and testing.
HIV-1 DNA levels after antiretroviral therapy in primary infection predict disease progression: the SPARTAC Trial James Williams 1,2,3, Jacob Hurst 1,2,3,

HIV-1 DNA levels after antiretroviral therapy in primary infection predict disease progression: the SPARTAC Trial James Williams 1,2,3, Jacob Hurst 1,2,3,
HIV, CD4, and More Karen Hutcherson Jenn Mann Elizabeth McCauley Michael Powers Courtney Wilson.

HIV, CD4, and More Karen Hutcherson Jenn Mann Elizabeth McCauley Michael Powers Courtney Wilson.
1 FDA Trial Design Requirements for HABP/VABP David M. Shlaes MD, PhD Anti-infectives Consulting, LLC Stonington, CT.

1 FDA Trial Design Requirements for HABP/VABP David M. Shlaes MD, PhD Anti-infectives Consulting, LLC Stonington, CT.
Overview Pediatric HIV Program & IMPAACT/ PACTG Vaccine Research Children’s National Medical Center, Washington, DC Dr.Hans ML Spiegel Director Special.

Overview Pediatric HIV Program & IMPAACT/ PACTG Vaccine Research Children’s National Medical Center, Washington, DC Dr.Hans ML Spiegel Director Special.
Mid-Career Faculty Development: Leadership Management Training Anne L. Taylor, MD John Lindenbaum Professor of Medicine Vice Dean for Academic Affairs.

Mid-Career Faculty Development: Leadership Management Training Anne L. Taylor, MD John Lindenbaum Professor of Medicine Vice Dean for Academic Affairs.
Studies of HIV Eradication: a Case for Using NHP Models Guido Silvestri, MD Yerkes National Primate Research Center Emory University School of Medicine.

Studies of HIV Eradication: a Case for Using NHP Models Guido Silvestri, MD Yerkes National Primate Research Center Emory University School of Medicine.
Case 1: 23-year-old Male Student Clinical Director, Division of Infectious Diseases Brigham and Women’s Hospital Professor of Medicine Harvard Medical.

Case 1: 23-year-old Male Student Clinical Director, Division of Infectious Diseases Brigham and Women’s Hospital Professor of Medicine Harvard Medical.
Anti-HIV Antibody Responses Reflect the Quantifiable HIV Reservoir Size Sulggi Lee, M.D., Ph.D. Assistant Professor of Medicine University of California,

Anti-HIV Antibody Responses Reflect the Quantifiable HIV Reservoir Size Sulggi Lee, M.D., Ph.D. Assistant Professor of Medicine University of California,
Primary HIV-1 Infection Pathogenesis, Diagnosis, and Treatment Summary of Evidence Martin Markowitz M.D. Clinical Director and Staff Investigator Aaron.

Primary HIV-1 Infection Pathogenesis, Diagnosis, and Treatment Summary of Evidence Martin Markowitz M.D. Clinical Director and Staff Investigator Aaron.
PK/PD Principles of Antimicrobials Michael J. Rybak, PharmD, MPH Professor of Pharmacy and Medicine Anti-Infective Research Laboratory.

PK/PD Principles of Antimicrobials Michael J. Rybak, PharmD, MPH Professor of Pharmacy and Medicine Anti-Infective Research Laboratory.
1 orBec ® (oral beclomethasone dipropionate) NDA 22-062 orBec ® (oral beclomethasone dipropionate) NDA 22-062 DOR BioPharma, Inc. Oncologic Drugs Advisory.

1 orBec ® (oral beclomethasone dipropionate) NDA orBec ® (oral beclomethasone dipropionate) NDA DOR BioPharma, Inc. Oncologic Drugs Advisory.
ART: When to Start? – Case Discussion Roy M. Gulick, MD, MPH Professor of Medicine Chief, Division of Infectious Diseases Weill Medical College of Cornell.

ART: When to Start? – Case Discussion Roy M. Gulick, MD, MPH Professor of Medicine Chief, Division of Infectious Diseases Weill Medical College of Cornell.

Similar presentations

Ads by Google