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.
|Pines, H A; Strathdee, S A; Hendrix, C W et al. (2018) Oral and vaginal HIV pre-exposure prophylaxis product attribute preferences among female sex workers in the Mexico-US border region. Int J STD AIDS :956462418793038|
|Pines, Heather A; Semple, Shirley J; Strathdee, Steffanie A et al. (2018) Vaginal washing and lubrication among female sex workers in the Mexico-US border region: implications for the development of vaginal PrEP for HIV prevention. BMC Public Health 18:1009|
|Figueroa, Dominique B; Madeen, Erin P; Tillotson, Joseph et al. (2018) Genetic Variation of the Kinases That Phosphorylate Tenofovir and Emtricitabine in Peripheral Blood Mononuclear Cells. AIDS Res Hum Retroviruses 34:421-429|
|Presnell, Aubrey L; Chuchuen, Oranat; Simons, Morgan G et al. (2018) Full depth measurement of tenofovir transport in rectal mucosa using confocal Raman spectroscopy and optical coherence tomography. Drug Deliv Transl Res 8:843-852|
|Carballo-Diéguez, Alex; Lentz, Cody; Giguere, Rebecca et al. (2018) Rectal Douching Associated with Receptive Anal Intercourse: A Literature Review. AIDS Behav 22:1288-1294|
|Hoang, Thuy; Date, Abhijit A; Ortiz, Jairo Ortiz et al. (2018) Development of rectal enema as microbicide (DREAM): Preclinical progressive selection of a tenofovir prodrug enema. Eur J Pharm Biopharm :|
|Hummert, Pamela; Parsons, Teresa L; Ensign, Laura M et al. (2018) Validation and implementation of liquid chromatographic-mass spectrometric (LC-MS) methods for the quantification of tenofovir prodrugs. J Pharm Biomed Anal 152:248-256|
|Carballo-Dieguez, Alex; Giguere, Rebecca; Lentz, Cody et al. (2018) Rectal Douching Practices Associated with Anal Intercourse: Implications for the Development of a Behaviorally Congruent HIV-Prevention Rectal Microbicide Douche. AIDS Behav :|
|Xiao, Peng; Gumber, Sanjeev; Marzinke, Mark A et al. (2018) Hypo-osmolar Formulation of Tenofovir (TFV) Enema Promotes Uptake and Metabolism of TFV in Tissues, Leading to Prevention of SHIV/SIV Infection. Antimicrob Agents Chemother 62:|
|Aung, Wutyi S; Bakshi, Rahul P; Breakey, Jennifer et al. (2018) Fecal Coliform Bacterial Detection to Assess Enema Adherence in HIV Prevention Clinical Studies. AIDS Behav :|
Showing the most recent 10 out of 23 publications