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

02573 DEVELOPING AN HIV MICROBICIDE BASED ON RNA INTERFERENCE

Lieberman, Judy
Song, E, Lee, S-K, Palliser, D, Shankar, P
CBR Institute and Department of Pediatrics, Harvard Medical School

Sexual transmission of HIV occurs when cell-free or cell-associated virus infects cells primarily via the CCR5 coreceptor, expressed on macrophages, dendritic cells and activated T lymphocytes. A microbicide that could be used vaginally to prevent sexual transmission would make a substantial contribution to controlling the spread of HIV. We are exploring the hypothesis that RNA interference (RNAi) can form the basis of an effective anti-HIV microbicide.

RNAi is an ancient, evolutionarily conserved, host defense against viruses and transposable elements, which uses small double-stranded RNAs, called small interfering RNAs (siRNA), to silence gene expression with exquisite specificity by targeted degradation of homologous mRNAs. There has been a lot of excitement about the therapeutic potential of RNAi to treat viral infection. A major obstacle is how to deliver siRNAs into cells in vivo. Duplex siRNAs targeting CCR5 and HIV gag delivered to monocyte-derived macrophages and activated T cells lead to prolonged gene silencing, lasting for weeks in macrophages, that completely inhibits de novo infection and suppresses viral replication in already infected cells. This suggests that duplex siRNAs might serve as the active component in a microbicide that might not need to be administered directly before sexual intercourse.

Many steps are needed to determine whether an siRNA-based microbicide is possible. These include in vivo delivery of siRNAs to dendritic cells, macrophages, and (if possible) lymphocytes in the genital mucosa of small animals, and demonstration that delivered siRNAs effectively inhibit HIV production. Delivery methods have to be safe and compatible with a formulation suitable for vaginal delivery that does not induce inflammation at the mucosa. Early proof-of-principle studies eventually need to be complemented by formal pharmacokinetics, toxicity and efficacy studies in small animals and primates. We will discuss our first steps to develop methods to deliver duplex siRNA to macrophages and dendritic cells in vivo in mice.

Dr Judy Lieberman
CBR Institute for Biomedical Research, 800 Huntington Avenue, Boston MA 02115 USA
(Telephone) 617 278-3381 (Fax) 617 278-3493 (E-mail) lieberman@cbr.med.harvard.edu