Microbicides 2004 Microbicides 200428-31 March 2004, Hilton London MetropoleThe conference42 million men, women and children worldwide were living with HIV by the end of December 2002 (source: UNAIDS), including five million newly-infected during that year alone. Another 45 million people will become infected between 2002 and 2010, unless the current transmission rates can be vastly reduced. Of the 42 million, 29.4 million live in sub-Saharan Africa and 58% of them are women. Not only are women more susceptible to HIV infection, many are powerless to insist on the use of condoms or other methods of protecting themselves. In this context, and with the knowledge that an effective HIV vaccine is unlikely to be available for several years, the need for an effective topical microbicide grows ever more urgent. 2004 should prove to be a landmark year in the field of microbicide development as the first Phase III trials of novel products are due to start – the next step along the road to making a microbicide available to the millions worldwide in desperate need of protection.The aims of the Microbicides 2004 conference are to:Report novel or innovative work in the microbicides fieldProvide updates on recent microbicides research, divided into three tracks: basic science, clinical science, and behavioural science (including public health and the microbicide marketplace)Provide a forum for the discussion of new developments in microbicide research including ethical, clinical, behavioural and methodological issuesPresent opportunities for knowledge-sharing between microbicide researchers, public-health workers and advocacy organisations.There will be an opening ceremony on the evening of Sunday 28 March at which politicians, policy makers and the international media are expected. The conference will run for a full three days, each of which will contain:Scientific overviews and presentations with plenary sessions, invited lecturers and presentations of original researchWorkshops to review issues unique to microbicides such as trial design and outcome measures, and ethical issues in the clinical trials of microbicidesPoster sessions. Focus on LondonFollowing the successful Microbicides conferences in Washington in 2000 and Antwerp in 2002, March 2004 sees the focus move to London.The venue is the Hilton Metropole Hotel, two minutes by taxi from Paddington station and the Heathrow Express, with a journey time from the airport of 15 minutes. The hotel is in walking distance of Hyde Park and London’s main shopping streets, and close to Imperial College. Accommodation will be available at the venue and other hotels in the vicinity.London in March offers a variety of diversions for out-of-conference relaxation, including sight-seeing and shopping; the arts and the theatre; and pubs, clubs and restaurants to suit every taste. Conference staff will be on hand to help delegates plan their spare time.To book your place or find out more information, e-mail info@microbicides2004.org.uk or telephone the Event Office on +44 (0) 20 7720 4411
Oral: invited speaker Oral: Track A Oral: Track B Oral: Track C Poster: Track A Poster: Track B Poster: Track C Abstract only Authors

02605 SULFATED POLYMERS TARGET HSV GLYCOPROTEIN B, PREVENT VIRAL BINDING, ENTRY, AND CELL-TO-CELL SPREAD AND MAY IMPACT MUCOSAL IMMUNITY

Cheshenko, Natalia1
Keller M2, MasCasullo V1, Jarvis G3, Cheng H3, John M1, Li J1, Hogarty K2, Anderson R4, Waller D5, Zaneveld L4, Profy A6, Klotman M2, and Herold B1
Departments of Pediatrics1 and Medicine2, Mount Sinai School of Medicine, New York, NY; Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA3; Department of Obstetrics and Gynecology, Rush University Medical Center, Chicago, IL4; Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL5; and Indevus Pharmaceuticals Inc., Lexington, MA6.

The observation that herpes simplex virus (HSV) and human immunodeficiency virus (HIV) bind heparan sulfate provided the rationale for development of sulfated or sulfonated polymers (SP) as topical agents. Although several have advanced to clinical trials, the mechanism of anti-viral activity and effects on soluble mediators of inflammation have not been evaluated. These studies address these gaps. Results indicate that PRO 2000, polystyrene sulfonate, cellulose sulfate, polymethylenehydroquinone sulfonate, and a mandelic acid condensation polymer designated SAMMA, which has no surfactant properties and does not contain sulfur, inhibit HSV infection 10,000 fold and are active against clinical isolates including an acyclovir resistant variant. The compounds form stable complexes with glycoprotein B and inhibit viral binding, entry, and cell-to-cell spread. The effects may be long lasting due to the high affinity and stability of the SP-viral complex, evidenced by surface plasmon resonance studies. The microbicides retain anti-viral activity in the presence of cervical secretions and over a broad pH range. There is little reduction in cell viability following repeated exposure of human endocervical cells to SP, although a reduction in secretory leukocyte protease inhibitor (SLPI) levels was observed. Prior to the initiation of large-scale clinical trials, rigorous evaluation of topical microbicides should include a thorough investigation of the changes in inflammatory cells, cytokines, and effects on host defenses following repeated application.

Assistant Professor, Natalia Cheshenko, PhD
Mount Sinai School of Medicine, One Gustave L.Levy Place, Box 1657, New York, NY 10029
(Telephone) 212 241 5272 (Fax) 212 426 4813 (E-mail) natalia.cheshenko@mssm.edu