Vaginal application of the PRO 2000 gel exerts activity against HIV and herpes simplex virus (HSV), investigators report in The Journal of Infectious Diseases.However, PRO 2000 and the many other microbicides being investigated to protect against HIV transmission face multiple challenges before they can made widely available, authors of a second Journal article note.PRO 2000 gel (Indevus Pharmaceuticals) is a synthetic compound that prevents HIV entry into cells by interacting with the proteins on the surface of the virus. While this agent has demonstrated the ability to inhibit HIV and HSV in cell cultures and in animal models, it was not known if it would be active after application in the human vagina.Dr. Betsy C. Herold, from Mount Sinai School of Medicine in New York, and colleagues recruited 20 HIV-infected women. Cell samples from the vagina and cervix were collected before and one hour after vaginal application of 2 milliliters of the PRO 2000 gel or an inactive placebo gel.Upon exposure to HIV, there was a significant reduction in HIV levels in cell samples from subjects treated with PRO 2000 compared with cells treated with the placebo.Herold’s group conducted a similar experiment using a virus that had surface proteins cloned from a HIV type that predominates “after sexual transmission and may be more readily transmitted via mucosal routes.” HIV infection was inhibited by greater than 99 percent in cervical and vaginal cells exposed to PRO 2000.The authors also noted potent anti-HSV activity with PRO 2000 compared with placebo."This trial demonstrates for the first time that a candidate microbicide is sufficiently bioavailable and retains substantial anti-HIV and anti-HSV activity after intravaginal application,” Herold and her team conclude.In the second paper, Drs. Darpun Dhawan and Kenneth H. Mayer, from Brown Medical School in Providence, Rhode Island, report that more than 30 other microbicides are under investigation, including 15 that are being studied in clinical trials.Strategies of candidate microbicides include disruption of the HIV membrane, alteration of the vaginal pH, inhibition of HIV receptors.Major obstacles that remain are developing ways for preclinical testing to evaluate safety and potential microbicidal resistance in the genital tract.Other challenges include the need to enroll thousands of HIV-uninfected, high-risk subjects in clinical trials that will last for several years and the development of agents to prevent transmission during anal intercourse.SOURCE: The Journal of Infectious Diseases, January 1, 2006.
