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Journal of Virology, October 2000, p. 9328-9332, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Combination of CCR5 and CXCR4 Inhibitors in Therapy of Human Immunodeficiency Virus Type 1 Infection: In Vitro Studies of Mixed Virus Infections†

Stefano Rusconi,1,2,* Simona La Seta Catamancio,1 Paola Citterio,1 Elisabetta Bulgheroni,1 Francesco Croce,1 Steven H. Herrmann,3 Robin E. Offord,4 Massimo Galli,1 and Martin S. Hirsch2

Istituto di Malattie Infettive e Tropicali, Università di Milano, Ospedale Luigi Sacco, Milan, Italy1; Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston,2 and Infectious Disease, Molecular Biology-Gene Expression, Genetics Institute Inc., Cambridge,3 Massachusetts; and Departement de Biochimie Medicale, Centre Medical Universitaire, Geneva, Switzerland4

Received 18 May 2000/Accepted 7 July 2000

We studied the combined anti-human immunodeficiency virus type 1 (HIV-1) effects of a derivative of stroma-derived factor 1beta (SDF-1beta ), Met-SDF-1beta , and a modified form of RANTES, aminooxypentane (AOP)-RANTES. The antiviral agents were tested singly or in combination at 95 and 99% virus inhibitory concentrations. Clinical R5 and X4 HIV-1 isolates were used. AOP-RANTES inhibited R5 but not X4 viruses, whereas Met-SDF-1beta had the opposite effect. Combinations of these compounds inhibited mixed infections with R5 and X4 viruses (95 to 99%), whereas single drugs were less inhibitory (32 to 61%). Combinations of R5 and X4 inhibitors are promising and deserve further evaluation.

* Corresponding author. Mailing address: Istituto di Malattie Infettive e Tropicali, Università di Milano, Ospedale Luigi Sacco, via GB Grassi 74,20157 Milan, Italy. Phone: 39.02.39042676. Fax: 39.02.3560805. E-mail: rusconi{at}mailserver.unimi.it.

dagger This paper is dedicated to the memory of Alessandro Caporali.

Journal of Virology, October 2000, p. 9328-9332, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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