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

02639_3 UC-781 BLOCKS LOCALISED INFECTION AND CELL DISSEMINATION PATHWAYS WITHIN HUMAN CERVICAL TISSUE

Watts, Patricia
Wallace, G., Mahmood, N., Harman, S., *Romano, J., Shattock, R.
St George’s Hospital Medical School, London, UK *Biosyn, Inc., Huntingdon Valley, Pa1. USA

Background: In the absence of an effective vaccine, microbicides provide a female controlled method of preventing HIV-1 infection that could significantly reduce worldwide transmission rates. UC-781 is a highly potent and selective thiocarboxanilide non-nucleoside reverse transcriptase inhibitors (NNRTI) of HIV-1. The compound exhibits high affinity for viral reverse transcriptase and is hydrophobic in nature, characteristics desirable for a microbicide. Thus, UC781 has potential as a lead candidate in microbicide development for both vaginal and rectal application. We have tested the hypothesis that UC781 can blockade both the localized infection of human cervical tissue, and dissemination of the virus.

Methods: In vitro activity and toxicity was determined by pretreatment of virus or target cells. The efficacy of UC781 to prevent localised mucosal infection and the potential uptake of infectious virus by migrating cells was assessed using an established ex-vivo, cervical explant model.

Results: UC781 potently inhibited HIV replication in cervical tissue explants and the transfer of infectious virus from migratory cells to coculture cells. In cervical explants pretreated with UC781, protection against viral challenge was still detectable 6 days post drug treatment, suggesting a potent memory effect. Pretreatment of tissue explants also demonstrated significant inhibition of viral dissemination by migratory cells. This inhibition was shown to occur by means other than the inhibition of viral attachment.

Conclusions: The NNRTI UC-781 demonstrates potent and prolonged activity against HIV-1 without being toxic to target cells. Thus, UC-781 is a promising candidate for continued pre-clinical and clinical development for use as a microbicide.

Miss Patricia Watts
Infectious Diseases, St George’s Hospital Medical School, London SW17 0RE. UK
(Telephone) +44 20 8725 5856 (Fax) +44 20 8725 3487 (E-mail) p.watts@sghms.ac.uk