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

02381 BLOCKADE OF ATTACHMENT AND FUSION RECEPTORS INHIBITS HIV-1 INFECTION OF HUMAN CERVICAL TISSUES

Hu Qinxue*
Watts P*, Frank I**, Williams V**, Moore J***, Pope M**, and Shattock R*
*St George’s Hospital Medical School, London, United Kingdom;**Population Council, New York, New York, USA; ***Weill Medical College of Cornell University, New York, New York, USA

Identification of cellular factors and primary target cells involved in mucsoal HIV-1 infection are crucial for understanding viral pathogenesis and development of effective prevention strategies. Accordingly, HIV-1 entry inhibitors were used to investigate the first line coreceptors for HIV-1 infection of human cervical tissue, the role of migratory cells and attachment receptors in HIV-1 dissemination in both cellular and mucosal infection. Blockade of CD4 alone, or CCR5 and CXCR4 together, inhibited localized mucosal infection. However, simultaneous blockade of both CD4 and mannose C-type lectin receptors (MCLR) including, but not limited to, DC-SIGN, was required to inhibit HIV-1 uptake and dissemination by migratory cells. In contrast, the direct targeting of HIV-1 by neutralizing mAb b12 and sCD4 fusion protein CD4-IgG2 was sufficient to block both localized infection and viral dissemination pathways. The observations were further confirmed in monocyte-derived dendritic cells and DC-SIGN+ cell line. Flow cytometric analysis and immunostaining of migratory cells revealed two major populations, CD3+CD4+HLA-DR- and CD3-CD14-HLA-DR+, with a significant proportion of the latter population also positive for DC-SIGN expression. The findings in current study provide the first demonstration that HIV-1 infects human cervix via CCR5 and CXCR4, and that both CD4 and MCLR on migratory cells may be involved in dissemination of infectious HIV-1 to other tissue sites. These studies have identified key targets for developing topical microbicide.

Mr Qinxue Hu
Department of Cellular and Molecular Medicine, Infectious Diseases, St George’s Hospital Medical School, Cranmer Terrace, London, SW17 ORE
(Telephone) 020 8725 0449 (Fax) 020 8725 3487 (E-mail) qhu@sghms.ac.uk