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Antimicrobial Agents and Chemotherapy, June 2007, p. 1972-1978, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01358-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Effect of Topical Microbicides on Infectious Human Immunodeficiency Virus Type 1 Binding to Epithelial Cells{triangledown}

Susan Roth,1,{dagger} Michael Monsour,2 Amanda Dowland,1,{ddagger} Patricia C. Guenthner,1 Kelly Hancock,1 Chin-Yi Ou,1 and Charlene S. Dezzutti1*

Laboratory Branch,1 Quantitative Sciences and Informatics Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 303332

Received 30 October 2006/ Returned for modification 29 December 2006/ Accepted 21 March 2007

Topical microbicides (cellulose acetate 1,2 benzene dicarboxylate [CAP], PRO 2000, SPL7013, and UC781) are being investigated to reduce the sexual transmission of human immunodeficiency virus type 1 (HIV-1). These products were shown to prevent the transfer of infectious HIV-1 from urogenital and colorectal epithelial cell lines to peripheral blood mononuclear cells. However, it was unclear if the topical microbicides rendered the virus noninfectious and/or reduced the binding to the epithelial cells. To test this, epithelial cells were cultured with HIV-1 in the presence or absence of topical microbicides or their placebos. The cells were washed, RNA lysates were made, and real-time PCR was performed for HIV-1. PRO 2000 and SPL7013 significantly (P < 0.0001) reduced the amount of bound HIV-1 to the colorectal epithelial cell line across clades A, B, C, and CRF01-AE. While none of the products reduced the binding of HIV-1 clades A and C to the urogenital cell line, CAP, PRO 2000, and SPL7013 significantly (P ≤ 0.002) reduced the binding of clades B and CRF01-AE. In general, PRO 2000 and SPL7013 placebos significantly (P < 0.0001) reduced the amount of bound HIV-1 but were less than the active products. UC781, its placebo, and hydroxyethyl cellulose (placebo for CAP) minimally affected the amount of bound HIV-1. These results suggest that rendering HIV-1 noninfectious may not correlate to the amount of HIV-1 bound to epithelial cells and possible shedding into mucosal secretions. Therefore, functional virological assays in addition to measuring viral RNA should be included when clinically evaluating topical microbicide use by infected persons.

* Corresponding author. Present address: University of Pittsburgh, Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, 204 Craft Avenue, Pittsburgh, PA 15213. Phone: (412) 641-3462. Fax: (412) 641-5290. E-mail: rsicsd{at}mwri.magee.edu

{triangledown} Published ahead of print on 2 April 2007.

{dagger} Present address: University of Pennsylvania, 508 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104.

{ddagger} Present address: Cass County Health Department, Bioterrorism Preparedness and Planning, 300 S. Main, Harrisonville, MO 64701.

Antimicrobial Agents and Chemotherapy, June 2007, p. 1972-1978, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01358-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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