3©\Drug Synergistic Interactions of Small Molecular Inhibitors of Hepatitis C Virus Replication

[Guest guest]

The Journal of Infectious Diseases 2008;197:42¨C45

0022-1899/2008/19701-00XX$15.00

DOI: 10.1086/524062

BRIEF REPORT

3©\Drug Synergistic Interactions of Small Molecular Inhibitors of Hepatitis C

Virus Replication

Christian Gr¨¹nberger,

L. Wyles,

A. Kaihara, and

T. Schooley

Department of Medicine, Division of Infectious Diseases, University of

California, San Diego, La Jolla

Received 9 March 2007; accepted 25 June 2007; electronically published 5

December 2007.

Potential conflicts of interest: R.T.S. has served as a consultant for Merck,

Gilead Sciences, GlaxoKline, and Vertex Pharmaceuticals.

Financial support: University of California San Diego Center for AIDS Research,

funded by National Institutes of Health program 5P30 (2005 developmental grant

AI©\36214); National Institute of Allergy and Infectious Diseases (grant

AI069989).

Reprints or correspondence: Wyles, 9500 Gilman Dr., MC 0711, La Jolla, CA

92093 (dwyles@...).

Small molecular inhibitors of hepatitis C virus (HCV) replication provide

remarkable potency, but the rapid selection of resistance mutations will require

that these agents be used in combination for clinical treatment. Using a model

HCV replicon system, we have extended prior in vitro studies of double

combinations of candidate small molecular inhibitors to studies evaluating the

simultaneous use of 3 agents. This was done in an effort to anticipate

conditions that might ultimately be required clinically. We formally demonstrate

synergistic antiviral activity with 3©\drug combinations in this model, further

supporting the concept of clinical investigations of combination therapy for HCV

infection.

http://www.journals.uchicago.edu/doi/abs/10.1086/524062

_________________________________________________________________

i¡¯m is proud to present Cause Effect, a series about real people making a

difference.

http://im.live.com/Messenger/IM/MTV/?source=text_Cause_Effect

[Guest guest]

The Journal of Infectious Diseases 2008;197:42¨C45

0022-1899/2008/19701-00XX$15.00

DOI: 10.1086/524062

BRIEF REPORT

3©\Drug Synergistic Interactions of Small Molecular Inhibitors of Hepatitis C

Virus Replication

Christian Gr¨¹nberger,

L. Wyles,

A. Kaihara, and

T. Schooley

Department of Medicine, Division of Infectious Diseases, University of

California, San Diego, La Jolla

Received 9 March 2007; accepted 25 June 2007; electronically published 5

December 2007.

Potential conflicts of interest: R.T.S. has served as a consultant for Merck,

Gilead Sciences, GlaxoKline, and Vertex Pharmaceuticals.

Financial support: University of California San Diego Center for AIDS Research,

funded by National Institutes of Health program 5P30 (2005 developmental grant

AI©\36214); National Institute of Allergy and Infectious Diseases (grant

AI069989).

Reprints or correspondence: Wyles, 9500 Gilman Dr., MC 0711, La Jolla, CA

92093 (dwyles@...).

Small molecular inhibitors of hepatitis C virus (HCV) replication provide

remarkable potency, but the rapid selection of resistance mutations will require

that these agents be used in combination for clinical treatment. Using a model

HCV replicon system, we have extended prior in vitro studies of double

combinations of candidate small molecular inhibitors to studies evaluating the

simultaneous use of 3 agents. This was done in an effort to anticipate

conditions that might ultimately be required clinically. We formally demonstrate

synergistic antiviral activity with 3©\drug combinations in this model, further

supporting the concept of clinical investigations of combination therapy for HCV

infection.

http://www.journals.uchicago.edu/doi/abs/10.1086/524062

_________________________________________________________________

i¡¯m is proud to present Cause Effect, a series about real people making a

difference.

http://im.live.com/Messenger/IM/MTV/?source=text_Cause_Effect