Genital herpes simplex virus (HSV) infections are a major global public health problem and women are disproportionately at risk of becoming infected. The prevalence of HSV type 2 (HSV-2) infections in the United States from 1999-2004 for persons aged 14-49 years was 17.0% with 11.2% of men infected and 22.8% of women. The global burden of HSV-2 is staggering. In 2003, it was estimated that 536 million people aged 15-49 years were living with HSV-2 infection worldwide. The number of newly infected people was 23.6 million, with the estimated prevalence being mostly higher in developing regions. The risk of HIV acquisition is three times greater in HSV-2 infected persons and the risk of HIV mother-to-infant transmission is higher in women co-infected with HSV-2. Antiviral drug therapy is effective in treating acute episodes and when used daily can prevent recurrences. However, antiviral drugs do not eradicate the latent infection and hence cannot cure HSV infections. Current methods for preventing genital herpes acquisition are limited and existing antiviral therapies reduce but do not eliminate the risk of transmission to a susceptible partner. Thus, effective biomedical strategies to prevent genital herpes acquisition are urgently needed;particularly for women since they are disproportionately at risk. Topical microbicides are products intended for vaginal use to protect women against sexually transmitted infections (STIs). Formulated SPL7013 (SPL7013 Gel, or VivaGel) is a novel candidate microbicide that has been shown to be safe and well tolerated in preclinical studies and a series of phase I trials. VivaGel is currently the only candidate microbicide being proposed for the prevention of genital HSV-2 infection. This proposed R34 planning grant will permit the comprehensive design of a Phase 2/2b trial to determine the effectiveness, safety, tolerability, and acceptability of vaginally applied SPL7013 Gel in preventing HSV-2 infection in women. As there are many parallels between trials designed to assess the efficacy of microbicides and vaccines we propose to build on the experience gained from HIV microbicide trials and from HSV vaccine trials including the NIAID sponsored HERPEVAC study. We have formed a collaboration of experienced researchers from Columbia University, Family Health International, and Starpharma to create the VivaGel Herpes Prevention Team. This team has a track record of working collaboratively, has significant expertise in the fields of HSV-2 and STI treatment and prevention, and the set-up and conduct of clinical trials. Thus, we are well positioned to manage the planning and development of all study materials for the clinical study known as "A Phase 2/2b Double-Blind, Randomized, Placebo-Controlled Study to Investigate the Safety and Efficacy of 3% SPL7013 Gel (VivaGel) in the Prevention of Genital Herpes Infection in Women". The following are examples of key areas that will be investigated during the planning process: duration of treatment, study population, clinical sites, study assessments, sample size, data management and statistical analysis, monitoring, and reporting. PUBLIC HEALTH RELEVANCE (provided by applicant): Genital herpes simplex virus (HSV) infections are a major global public health problem and women are disproportionately at risk of becoming infected. Formulated SPL7013 (SPL7013 Gel, or VivaGel) is currently the only candidate microbicide being proposed for the prevention of genital HSV-2 infection. This proposed R34 planning grant will permit the comprehensive design of a Phase 2/2b trial to determine the effectiveness, safety, tolerability, and acceptability of vaginally applied SPL7013 Gel in preventing HSV-2 infection in women.