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

02395 CHARACTERIZATION OF AN EX VIVO/IN VITRO INTESTINAL EXPLANT MODEL FOR RECTAL MICROBICIDE DEVELOPMENT.

McGowan, Ian*
Elliott, J*, Fuerst, M*, Watts, P#, Grivel, JC+, Shattock, R#, Margolis, L+, Anton, P*.
* The David Geffen School of Medicine at UCLA, Los Angeles, USA, #St George’s Hospital Medical School, London, UK, +NICHHD, NIH, Bethesda, USA

Introduction: In vitro models of rectal mucosal HIV-1 transmission are required for the preclinical evaluation of candidate rectal microbicides. Here we describe the use of endoscopic biopsies for this purpose. Methods: Endoscopic biopsies were collected 30cm from the anal margin from three HIV-1 seronegative subjects. Five of the biopsies were immediately processed for histology and flow cytometry and the remaining ten were each set up on Gelfoam rafts. Explants were harvested after 24 hours and one week of culture. Intestinal mononuclear cells were isolated from the remaining four explants by collagenase digestion. Cell viability was assessed using trypan blue exclusion and flow cytometry was performed after staining for CD45, CD3, CD4, and CD8. Trucount beads were used to quantify individual cell populations. Results: Intestinal biopsies processed immediately had normal morphology. After 24 hours of culture, significant deterioration of the mucosal architecture occurred with subtotal loss of intestinal crypts and epithelial detachment. At one week, stromal elements remained but intestinal crypts were absent. The mean cell viability at baseline was 91% (range 89 – 96), 63% at 24 hours (range 60 – 70) and 36% at 1 week (range 25 – 50). At 24 hours mean CD3+ lymphocyte count was 61% of baseline (range 59 – 63) and 50% of baseline (range 30-70) at 1 week. No preferential loss of CD4/CD8 subsets was seen. Challenge studies at Day 0 with R5 (SF162), X4 (LAV.04) and dual tropic R5/X4 (89.6) HIV-1 variants resulted in productive HIV -1 infection at Day 7 that was evidenced by increasing p24 levels in culture supernatant and by the accumulation of intracellular p24. Conclusions: These data suggest that endoscopic intestinal explants are a useful ex vivo/in vitro model for the evaluation of candidate rectal microbicides.

Dr. Ian McGowan
675 Charles E. Young Drive South, MRL 2736, Los Angeles, CA 90095-7019
(Telephone) 001-310-206-3580 (Fax) 001-310-206-9049 (E-mail) imcgowan@mednet.ucla.edu