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

02594 NEUTRALISING CAPACITY OF TMC120 (DAPIVIRINE) ON A RANGE OF CIRCULATING HIV-1 PRIMARY ISOLATES

Njai, Harr F*
Garcia, S* Andries, K **, De Béthune, M P**, Fransen, K*, Kestens, L*, Lewi, P J***, Janssen, P A J*** and Vanham G*
* Institute of Tropical Medicine, Antwerpen, Belgium, ** Tibotec, Mechelen, Belgium, *** Center For Molecular Design, Janssen Pharmaceutica, Vosselaar, Belgium.

The most ideal microbicidal must be able to neutralise a wide range of circulating HIV-1 subtypes to prevent new infections, especially in the third world. A pre-treatment system previously developed was used to study the neutralising capacity of TMC120 (R147681, dapivirine) and UC781, on Ba-L (NSI/R5) virus and six primary isolates (subtypes A, A/G, B, C and CRF02_AG) mostly from seropositive African individuals. Monocyte derived dendritic cells (MO-DC) and autologous CD4 T cells co-cultures were used as target cells, because they mimic early in vivo targets of the HIV sexual transmission (including interstitial DC and mucosal T cells). Cell-free virus was first immobilised on a poly-l-lysine (PLL) treated 96-well plate and pre-treated with drug for 1 hour. Afterwards, the drug was thoroughly washed away (6X); target cells were added and cultured for 2 weeks. Viral production was measured on supernatant with HIV antigen ELISA. Negative results were confirmed by showing absence of proviral DNA in the cells. TMC120 inhibited replication of Ba-L with an EC50 value of 49nM, it had a more potent inhibition capacity on the primary isolates with an EC50 value ranging from 22nM - <10nM. UC781 inhibited replication of the reference strain Ba-L with an EC50 value of 500nM. EC50 values on the primary isolates ranged from 34nM – 588nM. Both drugs were able to completely prevent HIV infection at 10nM-100nM (TMC120) or 1,000nM-10,000nM (UC781), hence TMC120 is a promising potentially sterilizing microbicide.

Drs Harr F Njai
155 Nationale Straat, Laboratory of Immunology, I T G, Antwerp 2000, Belgium
(Telephone) 0032 3 247 6226 (Fax) 0032 3 247 6230 (E-mail) hnjai@itg.be