The HIV/AIDS epidemic is expanding largely by way of heterosexual intercourse, with women constituting the largest population in a growing number of newly infected individuals.  The UNAIDS Initiative estimates that there are 17.6 million women infected with HIV/AIDS out of a total of over 39.4 million infected individuals as of December 2004.   They have also found that women are twice more likely than men to contract HIV-1 from a single act of unprotected sex, but they remain dependent on male cooperation to protect themselves from infection. AIDS experts estimate that microbicides, which are topical compounds applied prior to sexual intercourse to reduce or eliminate the risk of HIV-1 transmission, could prevent 2.5 million deaths over three years, especially when used as a female-controlled product.

In studies performed in collaboration with Novaflux Biosciences, Inc. (Princeton, NJ), we are assessing members of several families of compounds as potential microbicidal agents.  One of these compounds - hydroxypropyl methylcellulose trimellitate (HPMCT) - combines low in vitro cytotoxicity and potent anti-HIV-1 activity.  Our investigations are focused on assessing the efficacy of this compound, as well as determining its mechanism(s) of action.  My studies are based on our interest in determining the impact of various aspects of the cervicovaginal environment on the safety and effectiveness of HPMCT and other microbicides.  Relevant environmental variables include a wide pH range (normally 3.6-4.5 in most women, up to a neutral pH during and post sexual intercourse), the presence of neutralizing semen, cervicovaginal mucus, cervicovaginal proteins, and normal vaginal flora, including Lactobacillus sp..  Studies of these important determinants of microbicide effectiveness will aid in the preclinical development of a promising microbicidal compound that can be used to prevent transmission of HIV-1 to susceptible women during heterosexual intercourse.