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Antimicrobial Agents and Chemotherapy, May 2002, p. 1336-1339, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1336-1339.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Anti-Human Immunodeficiency Virus Interactions of SCH-C (SCH 351125), a CCR5 Antagonist, with Other Antiretroviral Agents In Vitro

Cécile L. Tremblay,1 Françoise Giguel,1 Christopher Kollmann,1 Yongbiao Guan,2 Ting-Chao Chou,2 Bahige M. Baroudy,3 and Martin S. Hirsch1*

Massachusetts General Hospital, Infectious Diseases Unit, Harvard Medical School, Boston, Massachusetts;,1 Memorial Sloan-Kettering Cancer Center, New York, New York,2 Schering-Plough Research Institute, Kenilworth, New Jersey3

Received 24 October 2001/ Returned for modification 9 January 2002/ Accepted 4 February 2002

SCH-C (SCH 351125) is a small-molecule antagonist of the human immunodeficiency virus type 1(HIV-1) coreceptor CCR5. It has in vitro activity against R5 viruses with 50% inhibitory concentrations ranging from 1.0 to 30.9 nM. We have studied anti-HIV-1 interactions of SCH-C with other antiretroviral agents in vitro. Synergistic interactions were seen with nucleoside reverse transcriptase inhibitors (zidovudine and lamivudine), nonnucleoside reverse transcriptase inhibitors (efavirenz), and protease inhibitors (indinavir) at all inhibitory concentrations evaluated. We have also studied antiviral interactions between the HIV-1 fusion inhibitor T-20 and SCH-C against a panel of R5 HIV-1 isolates. We found synergistic interactions against all the viruses tested, some of which harbored resistance mutations to reverse transcriptase and protease inhibitors. Anti-HIV-1 synergy was also observed between SCH-C and another R5 virus inhibitor, aminooxypentane-RANTES. These findings suggest that SCH-C may be a useful anti-HIV drug in combination regimens and that a combination of chemokine coreceptor/fusion inhibitors may be useful in the treatment of multidrug-resistant viruses.

* Corresponding author. Mailing address: Infectious Diseases Unit, Gray 5, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114. Phone: (617) 726-3815. Fax: (617) 726-7416. E-mail: mshirsch{at}partners.org.

Antimicrobial Agents and Chemotherapy, May 2002, p. 1336-1339, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1336-1339.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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