Penn Takes First Step in Development of Antibodies to HIV and Cure

MedicalResearch.com Interview with:

Katharine J Bar, MD Assistant Professor of Medicine Attending Physician, Infectious Diseases, Hospital of the University of Pennsylvania Physician, International Travel Medicine, Perelman Center for Advanced Medicine Director, Penn CFAR Viral and Molecular Core

Dr. Katharine J Bar

Katharine J Bar, MD
Assistant Professor of Medicine
Attending Physician, Infectious Diseases, Hospital of the University of Pennsylvania
Physician, International Travel Medicine, Perelman Center for Advanced Medicine
Director, Penn CFAR Viral and Molecular Core

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The passive administration of monoclonal antibodies has revolutionized many fields of medicine. Anti-HIV monoclonal antibodies are being explored as components of novel therapeutic and curative strategies, as they can both neutralize free virus and kill virus-infected cells. We sought to determine whether passive administration of an anti-HIV monoclonal antibody, VRC01, to chronically HIV-infected individuals on antiretroviral medications (ART) would be safe and well tolerated and could delay virus rebound after discontinuation of their ART.

MedicalResearch.com: What should readers take away from your report?

Response: We found that passive administration of VRC01 was safe and well tolerated in the 24 participants studied. Each participant achieved expected levels of VRC01 in their blood. The majority of participants, however, experienced viral rebound before 8 weeks. Thus, sustained virus suppression was not achieved, though there was a modest increase in the number of participants maintaining virus suppression at 4 weeks after ART interruption.

To explore why VRC01 was not able to maintain durable virus suppression, we studied viruses obtained from plasma sampled before ART was started (long before the study started) and rebound virus. VRC01 had been previously shown to neutralize ~90% of clinical HIV isolates and suppress viremia in animal models. In our participants, however, we found that many harbored virus that had pre-existing resistance to VRC01. Notably, in the minority of participants with longer periods of virus suppression, we did not detect pre-existing resistance.

Thus, we found that passive administration of VRC01 was safe and generated high plasma levels but did not maintain durable virus suppression due to the presence of pre-existing resistance.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: This study demonstrates the first step in the development of antibodies in HIV therapy and cure. Though passive infusion of a single antibody did not enable durable virus suppression, this study suggests that combinations of more potent antibodies that are currently in development may be able to provide durable virus suppression. If that is achieved, then the role of antibodies may play a key role as components of HIV therapy and functional cure strategies.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption

Katharine J. Bar, M.D., Michael C. Sneller, M.D., Linda J. Harrison, M.Sc., J. Shawn Justement, B.S., Edgar T. Overton, M.D., Mary E. Petrone, B.S., D. Brenda Salantes, B.S., Catherine A. Seamon, R.N., Benjamin Scheinfeld, B.A., Richard W. Kwan, P.A.-C., Gerald H. Learn, Ph.D., Michael A. Proschan, Ph.D., Edward F. Kreider, M.S., Jana Blazkova, Ph.D., Mark Bardsley, B.S.N., Eric W. Refsland, Ph.D., Michael Messer, R.N., Katherine E. Clarridge, M.D., Nancy B. Tustin, B.S., Patrick J. Madden, B.S., KaSaundra Oden, Ph.D., Sijy J. O’Dell, M.Sc., Bernadette Jarocki, B.S., Andrea R. Shiakolas, B.A., Randall L. Tressler, M.D., Nicole A. Doria-Rose, Ph.D., Robert T. Bailer, Ph.D., Julie E. Ledgerwood, D.O., Edmund V. Capparelli, Pharm.D., Rebecca M. Lynch, Ph.D., Barney S. Graham, M.D., Ph.D., Susan Moir, Ph.D., Richard A. Koup, M.D., John R. Mascola, M.D., James A. Hoxie, M.D., Anthony S. Fauci, M.D., Pablo Tebas, M.D., and Tae-Wook Chun, Ph.D.

N Engl J Med 2016; 375:2037-2050

November 24, 2016
DOI: 10.1056/NEJMoa1608243

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Leave a Reply

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.