CORE B Highly Active Antiretroviral Therapy (HAART), where antiretroviral (ARV) drugs are given in combination, has become the standard in treatment of HIV/AIDS. There is growing consensus that combinations of ARV agents are going to be needed for an optimally effective non-vaccine biomedical prevention (nBP) strategy for HIV. Difficulty in formulation and delivery of ARV combinations has limited the ability to determine efficacious and safe nBP products for vaginal topical application. Additionally, difficulty in determining adherence in topical microbicide clinical trials has limited the ability of these trials to measure efficacy of HIV prevention in human populations. The long-term goal of this IPCP-MBP effort is to develop intravaginal ring (IVR) formulations of multiple ARV drugs for prevention of sexual HIV transmission, emphasizing the needs of women in the developing world. The specific objective of Core B is to formulate a library of IVRs for delivering ARV combinations consisting of FDA-approved drugs and to provide these formulations to the component projects of the IPCP: Project 1-pharmacokinetics (PK), Project 2-safety, Project 3-efficacy, Project 4-(pre-Phase I) Exploratory Clinical Trial. Selection of the best performing candidate combination will be accomplished through a novel screening process involving iterative formulation development informed by PK, safety, and efficacy results. This optimized formulation will be transitioned into Project 5 to develop methods and capacity to manufacture clinical cGMP lots of the best performing candidate IVR at GMOs. The formulation efforts throughout this multi-faceted IND-enabling critical path will enable advancement of the lead formulation of the safest and most efficacious combination into post-IPCP Phase I clinical trials. In order to address the difficulty microbicide trials have encountered in assessing adherence to treatment, a novel adherence IVR has been developed that uses temperature measurement to determine and record hourly if an IVR is being worn. The prototype device will be optimized for use in women and evaluated in a pilot clinical study.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI113048-01
Application #
8765702
Study Section
Special Emphasis Panel (ZAI1-BP-A (M2))
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$393,957
Indirect Cost
$59,360
Name
Oak Crest Institute of Science
Department
Type
DUNS #
022470111
City
Pasadena
State
CA
Country
United States
Zip Code
91107
Guthrie, Kate M; Rosen, Rochelle K; Vargas, Sara E et al. (2018) User evaluations offer promise for pod-intravaginal ring as a drug delivery platform: A mixed methods study of acceptability and use experiences. PLoS One 13:e0197269
Vincent, Kathleen Listiak; Moss, John A; Marzinke, Mark A et al. (2018) Phase I trial of pod-intravaginal rings delivering antiretroviral agents for HIV-1 prevention: Rectal drug exposure from vaginal dosing with tenofovir disoproxil fumarate, emtricitabine, and maraviroc. PLoS One 13:e0201952
Medina-Colorado, Audrie A; Vincent, Kathleen L; Miller, Aaron L et al. (2017) Vaginal ecosystem modeling of growth patterns of anaerobic bacteria in microaerophilic conditions. Anaerobe 45:10-18
Gallay, Philippe A; Chatterji, Udayan; Kirchhoff, Aaron et al. (2017) Prevention of vaginal and rectal HIV transmission by antiretroviral combinations in humanized mice. PLoS One 12:e0184303
Moss, John A; Butkyavichene, Irina; Churchman, Scott A et al. (2016) Combination Pod-Intravaginal Ring Delivers Antiretroviral Agents for HIV Prophylaxis: Pharmacokinetic Evaluation in an Ovine Model. Antimicrob Agents Chemother 60:3759-66
Churchman, Scott A; Moss, John A; Baum, Marc M (2016) Accurate measurement of female genital tract fluid dilution in cervicovaginal lavage samples. J Chromatogr B Analyt Technol Biomed Life Sci 1017-1018:75-81
Blaser, Martin J; Cardon, Zoe G; Cho, Mildred K et al. (2016) Toward a Predictive Understanding of Earth's Microbiomes to Address 21st Century Challenges. MBio 7:
Baum, Marc M; Butkyavichene, Irina; Churchman, Scott A et al. (2015) An intravaginal ring for the sustained delivery of tenofovir disoproxil fumarate. Int J Pharm 495:579-587