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U-19 Microbicide Development Program

Overview Summary

This federally funded project focuses on HIV prevention and addresses the need to develop a rational, cost effective, and scientifically robust approach to the development of topical microbicides from preclinical to exploratory studies in humans. Three novel projects will explore distinct, but overlapping areas of microbicide and drug development research that, cumulatively, will define the future of rectal microbicide development. The international effort, led by investigators at UCLA, includes 18 investigators at six institutions in two countries.

The key premise driving the proposal is that receptive anal intercourse (RAI) is a common activity, playing a significant role in the transmission of HIV infection in women and men. Heterosexual RAI is common, with rates of 5-10% in US women and is considered to be the most common route of HIV transmission in men who have sex with men. Failure to acknowledge the role that RAI plays in the global AIDS pandemic is likely to limit the success of intervention strategies and compromise clinical trial efforts attempting to develop safe and effective vaginal microbicides.

This Microbicide DevelopmentProject (MDP) is know as a "U19" award, a collaborative effort with NIH and, importantly, involving industry up-front, to initiate coordinated, multidisciplinary research involving many of the world's experts in disciplines related to rectal microbicide development. We have focused our efforts on one class of microbicides, the reverse-transcriptase (RT) inhibitors (using three candidate drugs: PMPA, UC-781, and TMC-120), two of which are presently in clinical trials as vaginal microbicides. We have the support of three corporate sponsors (Biosyn, Inc., Gilead Sciences, and Tibotec-Virco) to initiate these efforts.

The "preclinical" development phase includes cell line, intestinal explant (biopsies) and macaque studies of microbicide safety and efficacy (Project 1). This project will enable the advancement of microbicide studies into exploratory human trials (Project 4). These studies will optimize microbicide safety evaluation in humans, provide initial ex vivo/in vitro efficacy data, and information about distribution and bioavailability of RT microbicides. The goal, over five years, will be to assess what are the most cost effective and predictive assays for use in future microbicide development. Project3 will target the behavioral correlates of RAI, and acceptability studies of candidate formulations.  These studies are crucial to developing a product that people will find acceptable and actually use. Their response will help guide the selection of the formulation used in final human trials. The information derived from these studies will be critical for RT microbicide development, and will also provide a rational basis for the development of other classes of rectal microbicides.

To facilitate the individual projects, there will be three Cores providing support:

  1. Administrative,
  2. Regulatory Compliance and Human Subject Safety, and
  3. Data Management and Biostatistics.