Fluid mechanics of functionality of anti-HIV microbicides

Andrew John Szeri, University of California, Berkeley
Basic-Applied Clinical

Recent reports (UNAIDS, 2006) clearly demonstrate that the global HIV/AIDS epidemic presents no sign of abating; it continues to spread at a rate of 15,000 new infections every day. Today, about 42 million people live with HIV/AIDS worldwide. Among them, 25 million live in sub-Saharan Africa. In Kenya, for instance, about 2.2 million people (15% of the population) are infected with HIV. As the epidemic spreads, it is infecting more and more women; globally, it is estimated that women represent approximately 65% of all those infected with HIV/AIDS. In fact, the leading risk factor for HIV among women in much of the world is to be the monogamous wife of an unfaithful or polygamous husband. AIDS has now become one of the most serious women's health issues globally and existing prevention methods for women at risk for HIV/AIDS are severely inadequate.

Worldwide, 90% of all adolescent and adult HIV transmissions have resulted from heterosexual intercourse. Although condom usage is effective, other preventative measures are required for deployment in societies where condom usage is less socially acceptable, or where women are not sufficiently empowered to insist on such protection. Microbicidal Formulations (microbicides) are a new class of products under development for topical prevention of HIV (or other sexually transmitted infections--STI) transmission during intercourse. These could target mucosal surfaces--in the vagina or rectum (for action by HIV entry inhibitors), or the underlying epithelium of those surfaces (for action by early replication inhibitors). In order for the active ingredients to work effectively, they must be adequately distributed to target tissue sites where HIV transmission occurs.

Our goal is to approach the design of microbicide vehicles rationally--and thereby optimize drug delivery. In order to do this, we need to develop understanding of what biophysical and biomechanical properties govern microbicide vehicle functionality. We focus on the coating of the epithelium. Our preliminary work has led to the development of a mathematical model of a realistic rheologically complex microbicide vehicle between compliant surfaces, suggestive of the vaginal coating problem. The model accounts for applied formulation volume, its non-Newtonian viscosity, tissue elasticity, and orientation of the vaginal axes. The model predicts the spread area and distribution of coating thickness vs. time after application. The model does not need to be anatomically detailed, as we are at the early stages of investigating tradeoffs in the design parameters, and the consequences for coating. The tradeoffs deduced through study of the model will be validated against experimental work of our collaborator, Prof. Katz, funded by NIH.

The project will involve an analysis of the trade-offs in non-Newtonian rheological properties in our model of undiluted microbicide vehicle between compliant vaginal surfaces and the effects on coating; will determine the changes in rheology associated with dilution of the microbicide vehicle with vaginal fluid exuded from the epithelium, and will be used to design new experiments to aid in the biophysical understanding of the spreading process. We will consider the findings vs. acceptability studies performed by our collaborator Dr. Bethany Young Holt. Taken together, this work will do much to help develop the nascent field of topical drug delivery, and to help reduce the rate of HIV infections.