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

02114_2 SPECTRUM OF HIV-1 INHIBITORY ACTIVITY OF SULFONATED POLYMERS, CANDIDATE TOPICAL MICROBICIDES

Klotman, Mary*
Scordi-Bello, I.*, Keller, M.*, Hogarty, K.*, Jarvis, G.**, Anderson, R.***, Waller, D.****, Zonenveld, L.J.D.***, Profy, A.*****, Herold, B.C.*
*Mt. Sinai School of Medicine , Ny, **University of California, San Francisco, Ca., ***Rush University, Il., **** University of Illinois, Il., *****Indevus Pharmaceuticals Inc., Ma

A number of candidate topical microbicides under development are within the same class of sulphated or sulfonated polysaccharides and include cellulose sulfate (CS), polysterene sulfonate (PSS), polymethelenehydroquinone sulfonate (PMHS) and Pro2000. In order to better understand the potential of this class of compounds, we compared these four compounds for their anti-HIV activity, cytotoxicity, activity in cervical lavage fluids and their antiviral mechanism(s) of action.

METHODS: Primary macrophages and T-cells as well as U87 cells engineered to express single co-receptors were treated with CS, PSS, PMHS and Pro2000 and challenged with laboratory-adapted or primary HIV-1 isolates as well as replication defective viruses carrying the luciferase indicator gene. The latter challenges were done with the addition of the compounds or AZT or small molecule entry inhibitors either at the same time as viral infection or varying amounts of time following infection. Finally, compounds were tested for their ability to block gp120 binding to the cell and for their ability to bind directly to gp120 using surface plasmon resonance (SPR) analyses with a BIAcore 3000 system.

RESULTS: All four compounds blocked HIV-1 replication in primary macrophages and CD4+ T-cells in the range of 10-100 ug/ml. The majority of the anti-HIV affect was during virus entry although there were some post-entry affects, particularly with PSS and CS. Each compound blocked binding of gp120 to CD4+/coreceptor positive U87 cells. PSS, CS and PMHS showed similar stable, high affinity binding to gp120 while CS could not be tested in this assay. Finally, all four compounds showed significant antiviral activity in the presence of cervical lavage fluid.

CONCLUSIONS: The compounds CS, PSS, PMHS and Pro 2000 all inhibit HIV-1 in primary macrophages and CD4+ cells in the presence of cervical lavage fluid. Consistent with their blocking of HIV-1 entry is their ability to block gp120 binding to the cell and their high affinity stable binding to gp120.

Dr. Mary E. Klotman
Mt. Sinai School of Medicine, 1 Gustave L. Levy Pl, Box 1090, New York N.Y. 10029
(Telephone) 212-241-2950 (Fax) 212-534-3240 (E-mail) mary.klotman@mssm.edu