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1 February 2007

Volume 195, Number 3
The Journal of Infectious Diseases 2007;195:387–391
© 2006 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2007/19503-0012$15.00
DOI: 10.1086/510531
BRIEF REPORT

Interruption of Enfuvirtide in HIV‐1–Infected Adults with Incomplete Viral Suppression on an Enfuvirtide‐Based Regimen

Steven G. Deeks,1

Jing Lu,3

Rebecca Hoh,1

Torsten B. Neilands,1

George Beatty,1

Wei Huang,2

Teri Liegler,1

Peter Hunt,1

Jeffrey N. Martin,1 and

Daniel R. Kuritzkes3

1University of California, San Francisco, San Francisco, and 2Monogram Biosciences, Inc., South San Francisco, California; 3Section of Retroviral Therapeutics, Brigham and Women’s Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts

Many antiretroviral drugs continue to exert an anti–human immunodeficiency virus (HIV) benefit in the presence of drug resistance mutations. The degree to which enfuvirtide exerts continued antiviral activity in the presence of incomplete viral suppression has not been defined. To address this question, 25 subjects interrupted enfuvirtide while remaining on a stable background regimen. Enfuvirtide interruption was associated with an immediate but limited increase in plasma HIV‐1 RNA levels. Enfuvirtide resistance waned rapidly in the absence of drug pressure and was no longer detectable by week 16 in most individuals. These data indicate that enfuvirtide has measurable antiviral activity in the setting of incomplete viral suppression. Although enfuvirtide resistance mutations are associated with significant fitness defects in vivo, the clinical significance of these mutations remains undefined.

Received 27 February 2006; accepted 7 June 2006; electronically published 21 December 2006.

Reprints or correspondence: Dr. Steven G. Deeks, San Francisco General Hospital, 995 Potrero Ave., San Francisco, CA 94110 ().

Cited by

Francesca Cossarini, Laura Galli, Caterina Sagnelli, Nicola Gianotti, Hamid Hasson, Massimo Clementi, Alessandro Soria, Stefania Salpietro, Adriano Lazzarin, Antonella Castagna. (2009) Survival of HIV-1 Infected Multidrug-Resistant Patients Recycling Enfuvirtide After a Previous Failure. JAIDS Journal of Acquired Immune Deficiency Syndromes 51:2, 179-184
Online publication date: 1-Jul-2009.
CrossRef
Alain Makinson, Jacques Reynes. (2009) The fusion inhibitor enfuvirtide in recent antiretroviral strategies. Current Opinion in HIV and AIDS 4:2, 150-158
Online publication date: 1-Apr-2009.
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Patricia Marr, Sharon Walmsley. (2008) Reassessment of enfuvirtide's role in the management of HIV-1 infection. Expert Opinion on Pharmacotherapy 9:13, 2349-2362
Online publication date: 1-Oct-2008.
CrossRef
Vincent Marconi, Sebastian Bonhoeffer, Roger Paredes, Jing Lu, Rebecca Hoh, Jeffery N Martin, Steven G Deeks, Daniel R Kuritzkes. (2008) Viral Dynamics and In Vivo Fitness of HIV-1 in the Presence and Absence of Enfuvirtide. JAIDS Journal of Acquired Immune Deficiency Syndromes 48:5, 572-576
Online publication date: 1-Sep-2008.
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Alessandro Soria, Mariangela Cavarelli, Stefania Sala, Anna Ida Alessandrini, Gabriella Scarlatti, Adriano Lazzarin, Antonella Castagna. (2008) Unexpected dramatic increase in CD4+ cell count in a patient with AIDS after enfuvirtide treatment despite persistent viremia and resistance mutations. Journal of Medical Virology 80:6, 937-941
Online publication date: 1-Jul-2008.
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David R. Bangsberg, Deanna L. Kroetz, Steven G. Deeks. (2007) Adherence-resistance relationships to combination HIV antiretroviral therapy. Current HIV/AIDS Reports 4:2, 65-72
Online publication date: 1-Jun-2007.
CrossRef
Caryn Morse and Frank Maldarelli. (2007) Enfuvirtide Antiviral Activity despite Rebound Viremia and Resistance Mutations: Fitness Tampering or a Case of Persistent Braking on Entering?. The Journal of Infectious Diseases 195:3, 318-321
Online publication date: 1-Feb-2007.
Citation-Full Text-PDF Version (164 kB)

  • Potential conflicts of interest: S.G.D. has received research support from Roche and has received honoraria from Monogram Biosciences, Trimeris, and Roche. W.H. is an employee of Monogram Biosciences. D.K. is a consultant to and has received honoraria from Monogram Biosciences and Roche. All other authors: none reported.

    Presented in part: 12th Conference on Retroviruses and Opportunistic Infections, Boston, 22–25 February 2005 (abstract 680).

    Financial support: National Institute of Allergy and Infectious Disease (grants AI052745, AI055273, and RR16482); California AIDS Research Center (grants CC99‐SF and ID01‐SF‐049); University of California, San Francisco/Gladstone Institute of Virology and Immunology Center for AIDS Research (grant P30 MH59037); Harvard Medical School Center for AIDS Research (grant P30 AI60354); Center for AIDS Prevention Studies (grant P30 MH62246); General Clinical Research Center at San Francisco General Hospital (grant 5‐MO1‐RR00083‐37). Phenotypic susceptibility testing and replicative capacity testing were performed by Monogram, Inc.

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