title: Effect of topical microbicides on infectious human immunodeficiency virus type 1 binding to epithelial cells.
abstract: 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.
authors.affiliation: University of Pittsburgh, Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, 204 Craft Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Roth
authors.forename: Michael
authors.initials: M
authors.lastname: Monsour
authors.forename: Amanda
authors.initials: A
authors.lastname: Dowland
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Guenthner
authors.forename: Kelly
authors.initials: K
authors.lastname: Hancock
authors.forename: Chin-Yi
authors.initials: CY
authors.lastname: Ou
authors.forename: Charlene S
authors.initials: CS
authors.lastname: Dezzutti
mesh_terms: D000813:Anilides / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D018938:Caco-2 Cells; D002482:Cellulose / Q000031:analogs & derivatives / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000821:virology; D050091:Dendrimers; D004847:Epithelial Cells / Q000821:virology*; D005663:Furans / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D009282:Naphthalenesulfonates / Q000494:pharmacology; D011107:Polylysine / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology; D012007:Rectum / Q000166:cytology / Q000821:virology; D013854:Thioamides; D014566:Urogenital System / Q000166:cytology / Q000821:virology
chemical_list: D000813:Anilides; D019380:Anti-HIV Agents; D000891:Anti-Infective Agents, Local; D050091:Dendrimers; D005663:Furans; D009282:Naphthalenesulfonates; C120231:PRO 2000; D011108:Polymers; D013854:Thioamides; C496530:cellulose acetate 1,2-benzenedicarboxylate; D011107:Polylysine; D002482:Cellulose; C480351:astodrimer; C100668:UC-781