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1 April 2005

Volume 191, Number 7
The Journal of Infectious Diseases 2005;191:1155–1163
© 2005 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19107-0019$15.00
DOI: 10.1086/427993
MAJOR ARTICLE

T‐1249 Retains Potent Antiretroviral Activity in Patients Who Had Experienced Virological Failure while on an Enfuvirtide‐Containing Treatment Regimen

Jacob P. Lalezari,1

Nicholaos C. Bellos,2

Kunthavi Sathasivam,3

Gary J. Richmond,4

Calvin J. Cohen,5

Robert A. Myers, Jr.,6

David H. Henry,7

Claire Raskino,9

Tom Melby,8

Hugh Murchison,8

Ying Zhang,8

Rebecca Spence,8

Michael L. Greenberg,8

Ralph A. DeMasi,8 and

G. Diego Miralles,8 for the

T1249‐102 Study Group

1Quest Clinical Research, San Francisco, California; 2South West Infectious Diseases, Dallas, Texas; 3Elizabeth Taylor Medical Center, Washington, DC; 4North Broward Hospital District, Fort Lauderdale, Florida; 5Community Health Initiative of New England, Boston, Massachusetts; 6Phoenix Body Positive, Phoenix, Arizona; 7Pennsylvania Oncology and Hematology, Philadelphia; 8Trimeris, Durham, North Carolina; 9Roche, Welwyn, United Kingdom

Background.T‐1249 is a 39–amino acid synthetic peptide fusion inhibitor (FI) shown to preserve antiretroviral activity in vitro against human immunodeficiency virus (HIV) isolates that have decreased susceptibility to enfuvirtide (ENF).

Methods.A 10‐day phase 1/2 study of the safety and antiretroviral activity of T‐1249 was conducted in 53 HIV‐1–infected adults with detectable viremia while on an ENF‐containing treatment regimen.

Results.From FI‐naive baseline levels, the geometric mean (GM) decrease in susceptibility to ENF was 116.3‐fold, and the GM decrease in susceptibility to T‐1249 was 2.0‐fold. Patients continued to administer their failing treatment regimen but replaced ENF with T‐1249 at a dose of 192 mg/day. T‐1249 was generally well tolerated; injection site reactions, which were generally mild, were the most commonly reported adverse event (64% of patients). The median change from levels of HIV‐1 RNA at baseline to levels on day 11 was −1.26 log10 copies/mL (95% confidence interval, −1.40 to −1.09 log10 copies/mL); on day 11, a decrease from baseline HIV‐1 RNA levels of 1.0 log10 copies/mL was seen in 73% of patients. Antiretroviral activity, as measured by levels of HIV‐1 RNA, was not predicted by baseline susceptibility to T‐1249 or to ENF; genotypic substitutions that emerged during T‐1249 treatment were identified in virus from some patients.

Conclusions.These results indicate that FIs constitute an expanding class of antiretroviral agents with the potential to be sequenced.

Received 1 June 2004; accepted 17 September 2004; electronically published 22 February 2005.

Reprints or correspondence: Dr. G. Diego Miralles, Trimeris, 3500 Paramount Dr. Morrisville, NC 27560 ().

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  • Presented in part: 10th Conference on Retroviruses and Opportunistic Infections, Boston, 10–14 February 2003 (abstract 14LB); 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, 14–17 September 2003 (abstract H‐444).

    Financial support: Trimeris and Roche.

    Potential conflicts of interest: D.H.H. is a member of the Roche Speakers' Bureau. C.J.C. has received consulting fees and grant support from Roche. T.M., H.M., Y.Z., R.S., M.L.G., R.A.D., and G.D.M. are full‐time employees of Trimeris, a study sponsor. C.R. is a full‐time employee of Roche, a study sponsor.

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