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Antimicrobial Agents and Chemotherapy, May 2005, p. 1830-1836, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.1830-1836.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Combination of Candidate Microbicides Cellulose Acetate 1,2-Benzenedicarboxylate and UC781 Has Synergistic and Complementary Effects against Human Immunodeficiency Virus Type 1 Infection

Shuwen Liu, Hong Lu, A. Robert Neurath, and Shibo Jiang*

Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York

Received 10 August 2004/ Returned for modification 8 November 2004/ Accepted 31 December 2004

The combination of two candidate microbicides, cellulose acetate 1,2-benzenedicarboxylate (CAP), a polymer that blocks human immunodeficiency virus type 1 (HIV-1) entry by targeting gp120 and gp41, and UC781, a tight-binding HIV-1 reverse transcriptase inhibitor (RTI), resulted in effective synergy for inhibition of MT-2 cell infection by HIV-1IIIB, a laboratory-adapted virus strain. The 95% effective concentration values for the combination were reduced about 15- to 20-fold compared with those corresponding to the single compounds. The combination of CAP and UC781 is also synergistic in inhibiting infection of peripheral blood mononuclear cells by a primary HIV-1 isolate, 92US657. Combinations of CAP with other RTIs, such as efavirenz or zidovudine, also had significant synergistic effects on the inhibition of HIV-1 infection. In addition, CAP and UC781 had complementary effects against HIV-1 infection since (i) CAP inhibited infection by the UC781-resistant strain HIV-1IIIB A17 and (ii) pretreatment of MT-2 cells with UC781, but not CAP, abolished subsequent infection after removal of the compound. This suggests that the combination of CAP and UC781 represents a promising candidate microbicide for prevention of sexual transmission of HIV-1.

* Corresponding author. Mailing address: Lindsley F. Kimball Research Institute, New York Blood Center, 310 E 67th St., New York, NY 10021. Phone: (212) 570-3058. Fax: (212) 570-3099. E-mail: sjiang{at}nybloodcenter.org.

Antimicrobial Agents and Chemotherapy, May 2005, p. 1830-1836, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.1830-1836.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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