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:
- Administrative,
- Regulatory Compliance and Human Subject Safety, and
- Data Management and Biostatistics.
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