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

03265 A NOVEL EX VIVO MODEL OF VAGINAL HIV-1 TRANSMISSION REVEALS PARALLEL RATHER THAN SEQUENTIAL TARGETING OF INTRAEPITHELIAL LANGERHANS AND T CELLS

Hladik, Florian*°
Sakchalathorn P.*, Ballweber L.*, Lentz G.°, Eschenbach D.°, McElrath M.J.*°
*Fred Hutchinson Cancer Research Center, °University of Washington School of Medicine

Sexual HIV transmission is thought to occur with the initial uptake of virions by mucosal dendritic cells (DCs), followed by the delivery of HIV to CD4+ T cells. This sequential model has arisen primarily from studies utilizing monocyte-derived DCs and epidermal Langerhans cells (LCs) rather than direct observations in the human genital tract, which are precluded by technical limitations and ethical considerations. Here, we introduce a novel ex vivo model that elucidates the initial intraepithelial transmission events. Vaginal epithelial sheets were obtained without the use of digestive enzymes by gentle ex vivo suction blistering of surgically excised mucosa. We then challenged these sheets with green-fluorescence protein (gfp)-tagged infectious virions by spinoculation. Examination by confocal microscopy revealed that both R5-tropic HIV-1 JR-CSF and X4-tropic HIV-1 LAI simultaneously bound to intraepithelial vaginal T cells and LCs. Electron microscopy and blocking studies with monoclonal antibodies and mannan demonstrated that HIV-1 entered both cell types via CD4 and coreceptor-mediated fusion. In trans viral passage and C-type lectin receptors did not significantly contribute to this process. Thus, although vaginal LCs were also able to sequester intact virions in endosomes, our findings point to a parallel rather than a sequential mode of transmission, where infection occurs simultaneously in both intraepithelial LCs and T cells.

Florian Hladik, MD, PHD
Fred Hutchinson Cancer Research Center, Program in Infectious Diseases, 1100 Fairview Ave. N., P.O. Box 19024, D3-100, Seattle, WA 98109-1024
(Telephone) 1-206-667-6836 (Fax) 1-206-667-4411 (E-mail) fhladik@fhcrc.org