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

02442 PMPA- NNRTI COMBINATION STUDIES DEMONSTRATE POTENT SYNERGISM AGAINST HIV-1 INFECTION IN VITRO

Schader, Susan*
Klasse, P.J.**, Harman, S.*, Watts, P.*, Shattock, R.*
*St. George’s Hospital Medical School, London, United Kingdom, **Department of Microbiology and Immunology, Cornell University, Weill Medical College, New York, N Y

Background: Combination products may maximise microbicide efficacy through: blockade of multiple targets involved in HIV transmission; increased activity through potential synergy; and minimizing potential development of resistance. We have investigated the synergistic potential of PMPA (9-[2-(Phosphonomethoxy)Propyl] Adenine), an acyclic nucleoside phosphonate (NRTI), with non- nucleoside reverse transcriptase inhibitors (NNRTIs) and PRO 2000, a candidate polyanion microbicide.

Methods: Synergistic potential was evaluated in cellular and cervical explant studies. Cells or tissue were treated with each drug alone or in a fixed ratio combination for 1 hour. R5 or X4 HIV-1 isolates were then added and incubated for a further 2 hours with subsequent washing to remove free drug and virus. Viral replication was monitored by measurement of supernatant reverse transcriptase activity (RT), p24 release or quantitative proviral PCR. The 50% inhibitory concentration (IC50) for drugs alone and in combination was determined. Analysis of combined effects was accomplished using the median effect principle developed by Chou and Talalay, (Calcusyn, Biosoft).

Results: PMPA in combination with UC781 demonstrated anti- HIV- 1 synergism with combination indices <1 in RT based assays, while PMPA in combination with PRO 2000 did not. These results have been extended in a cervical explant model to evaluate the efficacy of single and combination drugs against HIV infection and potential dissemination by migratory cells.

Conclusions: PMPA, in combination with candidate NNRTIs demonstrate good anti-HIV-1 activity in vitro and the capability of these drugs to demonstrate synergy is promising. Although PRO 2000 in combination with PMPA might improve the effect of PRO 2000, the combination is not synergistic and would not enhance the efficacy of PMPA.

Ms. Susan Schader- Plesman
St. George’s Hospital Medical School, Cranmer Terrace, Tooting, London, SW17 0RE
(Telephone) (0)20 8725 1432 (Fax) (0)20 8725 3487 (E-mail) sschader@sghms.ac.uk