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

02460 UC781 PROTECTS EX VIVO LYMPHOID TISSUE FROM HIV-1 INFECTION.

Kiselyeva,Yana
Watts, P*, Margolis, L, & Shattock, R*
Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
*St. George Hospital Medical School, London, UK

Thiocarboxanilide UC781 is a potent non-nucleoside HIV-1 RT inhibitor that is being developed as a microbicide (Biosyn, Huntington Valley, PA). We studied anti-viral activity of this compound against HIV-1 variants of different coreceptor tropisms in human lymphoid tissue ex vivo. This system supports productive HIV-1 infection without exogenous stimulation. UC781 inhibits HIV-1 replication in a dose-dependent manner. If it is present constantly at concentrations of 1 mM, UC781 completely inhibits R5SF162 and X4LAV.04 HIV-1 strains, while 0.1 mM totally inhibits only R5SF162.

To test the potential “memory” effect of the drug on virus replication, human lymphoid tissue was pretreated for 2 h with UC781 (10 mM and 1 mM), thoroughly washed, and than infected with HIV-1 either immediately or after 24 h or 48 h. Viral replication was assessed 10–12 days post-infection. Under these conditions, 10-mM UC781 completely inhibited both R5 and X4 replication. At 1 mM, UC781 inhibited X4 replication (by 50%) only when tissues were inoculated with virus immediately after drug removal; it did not inhibit replication if tissue was inoculated 24–48 h after drug removal. In contrast, R5 replication was inhibited by 95% when tissue was inoculated with virus 24 h after drug removal and by 90% 48 h after drug removal.

Thus, UC781 is a strong inhibitor of HIV-1 replication in human lymphoid tissue ex vivo. Brief treatment of tissues with UC781 renders them resistant to HIV infection even in the absence of this drug. R5 HIV-1, which is known to transmit infection, is more sensitive to UC781 inhibition than is X4.

Yana Kiselyeva
SRC VB VECTOR Research Institute of Molecular Biology, Koltsovo, Novosibirsk region, 630559, Russia
(Telephone) 7(383-2)36-50-17 (Fax) 1-301-480-0857 (E-mail) yakiseleva@pochta.ru