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

02421 MICROBICIDAL DETERGENTS INCREASE HSV SUSCEPTIBILITY IN MICE W/O CAUSING VISIBLE EPITHELIAL DEFECTS

Cone, Richard A.*#  
Hoen T.E.*, Wang X.X.*, & Moench T.R.# * Department of Biophysics, Johns Hopkins University, #Reprotect, Inc., Baltimore Md, U.S.A.

Background: To block HSV infections, a detergent must be delivered at a concentration that rapidly disrupts epithelial cell membranes, and even at much lower concentrations, detergents still disturb cellular functions. In the mouse rectum, N9 (a nonionic detergent) delivered at a viricidal concentration rapidly injures columnar epithelium cells and later markedly increases rectal susceptibility to HSV (Phillips and Zacharopoulos, Contraception 1998). In the vagina of the mouse, when pre-treated with Depo-Provera to transform the entire epithelium to become columnar, a single application of N9 causes a long-lasting inflammatory response (Milligan et al, STDs, 29:597-605, 2002) and also causes a prolonged and marked increase in susceptibility to HSV (Abusuwwa et al, Microbicides 2002, Antwerp). Here we report tests of four major categories of detergents that are now used as spermicides and/or are being evaluated as microbicides: cationic (benzlkonium chloride), anionic (SDS – sodium dodecyl (lauryl) sulfate), zwitterionic (cetyl betaine; myristyl dimethylamine oxide), and nonionic (nonoxynol-9). Methods: Mice pretreated with DepoProvera were exposed to a single application of the test detergent (2% in PBS). (This concentration was selected since it is the minimal concentration of N9 that provides detectable protection of mice against HSV infection.) Twelve hours after delivering the test detergent, mice were inoculated with a low-dose of virus (0.1 Vaginal Infectious Dose50 of HSV-2). One group of control mice (PBS w/o detergent) was inoculated with this same low-dose inoculum, and another control group with a high-dose inoculum (10 Vaginal Infectious Dose50). Infections were detected 3 days later by culturing vaginal lavage fluid on human foreskin fibroblasts. Results: Every detergent tested to date markedly increased the susceptibility of mice (range:10-30 fold) when challenged 12 hours after one exposure to the detergent. Also, this increased susceptibility occurred without inducing epithelial defects as visualized by colposcopy. Conclusions: A detergent applied only once to a columnar epithelium can cause a prolonged and marked increase in the susceptibility of the epithelium to HSV. Our results suggest that in clinical trials, this toxic effect on columnar epithelium would not be detected by colposcopy.

Richard Cone
Department of Biophysics, Johns Hopkins University, Baltimore MD 21218, USA.
(Telephone) 410-516-7259 (Fax) 410-516-6597 (E-mail) cone@jhu.edu