The Development of a Rectal Enema As Microbicide (DREAM) Program addresses the critical need to develop a highly effective, safe, and acceptable microbicide enema with the promise of greater adherence as a more behaviorally-transparent alternative for the prevention of rectal HIV infection. The overall goal of the program is to develop a single dose rectal enema to deliver a tenofovir (TFV) prodrug capable of providing one week of protection. This strategy builds upon proven high levels of efficacy of TFV-based pre-exposure prophylaxis (PrEP) in adherent persons and directly targets the greatest weakness of PrEP regimens - prophylactic failure due to poor adherence. Given the common practice of rectal douching with an enema prior to receptive anal sex, we have selected a dosing strategy requiring little or no behavioral change compared to oral and other topical approaches. Topical delivery also significantly reduces systemic exposure compared to oral and injectable approaches. The purpose of this Core is to provide regulatory and technical expertise to maintain and manage consistent compliance with the regulatory requirements for all projects in the DREAM U19. The Core includes two separate but complementary components: (i) industry oversight of the preclinical work required for IND studies, including interactions with FDA (provided by our industry sponsor CONRAD);and (ii) management and oversight of regulatory compliance, training, and implementation of pre-phase 1 clinical trials (which will be completed by the dedicated teams at UCLA and Magee-University of Pittsburgh) through the following specific aims:
Specific Aim 1 : To provide regulatory support and oversight.
Specific Aim 2 : To establish and maintain Quality Management practices and processes throughout all program Projects and Cores.
A safe, effective HIV pre-exposure prophylaxis strategy with high levels of adherence is urgently needed to protect men and women at highest risk of HIV infection from anal sex. We propose development of a TFV enema to reduce HIV transmission associated with anal sex. This Core provides regulatory oversight for the ethical conduct of clinical and animal research.