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

02603 EFFECT OF 0.5% PRO 2000/5 GEL ON INFECTIOUS HIV-1 AND INFLAMMATORY MEDIATORS IN CERVICOVAGINAL SECRETIONS

Keller, Marla1
Hogarty K1, Goldberg C2, Kasowitz A1, Cheshenko N2, Luckay A1, Profy A3, Klotman M1, Herold B2
Departments of Medicine1 and Pediatrics2, Mount Sinai School, Medicine, New York, NY; Indevus Pharmaceuticals Inc., Lexington, MA3

PRO 2000/5 has been shown to inhibit HIV and other STI in cell culture and in animal models. However, there is as yet no data showing that any microbicide exhibits anti-viral activity in vivo. We are conducting a prospective double-blind placebo-controlled study among 20 HIV-infected women to assess whether a single 2-g intravaginal dose of 0.5% PRO 2000/5 Gel (P) reduces levels of infectious HIV present in cervicovaginal lavage (CVL) fluid collected one hour after application. A secondary objective is to assess the acute inflammatory response to a single application of 0.5% PRO 2000/5 Gel (P) by testing the CVL for inflammatory cells, IL-1b and IL-8. Inclusion criteria include age between 18 and 45, HIV-1 RNA &Mac179; 50,000 copies/ml, and a normal Pap smear within 6 months of screening. Exclusions include pregnancy, recent UTI or STI, and sexual intercourse or use of other vaginal products within 48 h of screening. Given the variability in the ability to reproducibly recover a subject’s own infectious HIV from CVL, the anti-viral activity in CVL will be assessed by spiking with serial dilutions of HIV and quantifying the virus recovered. Serial two-fold dilutions of CVL supernatants collected at screening (2-3 days before) and 1h after application of PRO 2000/5 or placebo gel will be spiked with dilutions of HIV-1 and then inoculated onto susceptible cells. A dilution of CVL that inhibits or neutralizes virus will be determined. Additionally, the subject’s own virus will be cultured directly from supernatant and cell pellets obtained before and after PRO 2000/5 or placebo gel application. A peroxidase test on the cell suspension will be used to quantify PMNs; IL-1b and IL-8 will be measured using commercial ELISA kits. In preliminary studies, infectious virus has been reproducibly and successfully recovered after spiking CVL samples with serial dilutions of virus. In addition, the anti-HIV activity of serial two-fold dilutions of PRO 2000/5 diluted in vitro in CVL has been established starting with an initial concentration of 500 mg/ml and spiked with 20 ng of p24/ml of replication defective JRFL-pseudotyped virus expressing a luciferase indicator gene. A 1:512 dilution or 0.977 mg/ml of PRO 2000 in CVL inhibited infection by the JRFL-pseudotyped virus. This strategy is a mechanism for testing in vivo the efficacy of a microbicide before embarking on large-scale clinical trials.

Assistant Professor, Marla Keller, MD
Mount Sinai School of Medicine, One Gustave Levy Place Box 1090, New York, NY 10029
(Telephone) 212 241 5890 (Fax) 212 534 3240 (E-mail) marla.keller@mssm.edu