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Journal of Virology, October 2007, p. 11016-11031, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.01340-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Adjunctive Passive Immunotherapy in Human Immunodeficiency Virus Type 1-Infected Individuals Treated with Antiviral Therapy during Acute and Early Infection{triangledown} ,{dagger}

Saurabh Mehandru,1 Brigitta Vcelar,2 Terri Wrin,3 Gabriela Stiegler,2 Beda Joos,4 Hiroshi Mohri,1 Daniel Boden,1 Justin Galovich,3 Klara Tenner-Racz,5 Paul Racz,5 Mary Carrington,6 Christos Petropoulos,3 Hermann Katinger,2,7 and Martin Markowitz1*

Aaron Diamond AIDS Research Center, The Rockefeller University. 455 First Avenue, New York, New York 10016,1 Polymun Scientific, Nußdorfer Lände 11, A-1190 Vienna, Austria,2 Monogram Biosciences Inc., 345 Oyster Point Boulevard, South San Francisco, California,3 Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Zürich, Switzerland,4 Bernhard-Nocht Institut fur Tropenmedizin, 20359 Hamburg, Germany,5 Laboratory of Genomic Diversity, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702,6 Institute of Applied Microbiology, University of Natural Resources and Applied Life Sciences, Vienna, Austria7

Received 19 June 2007/ Accepted 26 July 2007

Three neutralizing monoclonal antibodies (MAbs), 2G12, 2F5, and 4E10, with activity in vitro and in vivo were administered in an open-label, nonrandomized, proof-of-concept study to attempt to prevent viral rebound after interruption of antiretroviral therapy (ART). Ten human immunodeficiency virus type 1-infected individuals identified and treated with ART during acute and early infection were enrolled. The first six patients were administered 1.0 g of each of the three MAbs per infusion. The remaining four patients received 2G12 at 1.0 g/infusion and 2.0 g/infusion of 2F5 and 4E10. The MAbs were well tolerated. Grade I post-partial thromboplastin time prolongations were noted. Viral rebound was observed in 8/10 subjects (28 to 73 days post-ART interruption), and 2/10 subjects remained aviremic over the course of the study. In seven of eight subjects with viral rebound, clear resistance to 2G12 emerged, whereas reductions in the susceptibilities of plasma-derived recombinant viruses to 2F5 and 4E10 were neither sustained nor consistently measured. Viral rebound was associated with a preferential depletion of CD4+ T cells within the gastrointestinal tract. Though safe, the use of MAbs generally delayed, but did not prevent, virologic rebound. Consideration should be given to further pilot studies with alternative combinations of MAbs and perhaps additional novel treatment modalities.

* Corresponding author. Mailing address: Aaron Diamond AIDS Research Center, 455 First Avenue, 7th Floor, New York, NY 10016. Phone: (212) 448-5020. Fax: (212) 725-1126. E-mail: mmarkowitz{at}adarc.org

{triangledown} Published ahead of print on 8 August 2007.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org.

Journal of Virology, October 2007, p. 11016-11031, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.01340-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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