This Proposal is part of a Program project grant focusing on combination antiretroviral microbicides formulated in a gels optimized or vaginal use and for rectal use for the prevention of sexually-tranmitted HIV infection. This project includes a series of pre-Phase I studies that will assess the pharmacokinetic, pharmacodynamic (anti-HIV efficacy and toxicity), and acceptability characteristics of a combination microbicide simultaneously.
Specific Aim 1. Methods Validation. Develop and validate assays for 0528 in blood, tissue, and luminal fluid, improve tenofovir intracellular assay sensitivity, verify compatibility of radiolabels with gel formulations, and cross-validate HIV explant methods with existing IP/CP funded labs for comparability.
Specific Aim 2. Impact of Rectal Gel Volume on Distribution Comparative pre-Phase I Study. Compare colonic distribution and permeability with 3.5 mL v. 10 mL rectal placebo gel to inform final dose formulation for pre-Phase I clinical studies in Aim 3 &Aim 4.
Specific Aim 3. Exploratory 0528 gel pre-Phase I PK/PD/Acceptability Study. Compare the spatiotemporal distribution (cervicovaginal, rectal, systemic), explant tissue anti-HIV effect, toxicological assessment, and acceptability of the 0528 candidate gel formulation for vaginal and rectal dosing in an exploratory pre-Phase I clinical study.
Specific Aim 4. Exploratory combination 0528/tenofovir pre-Phase I PK/PD/Acceptability Study. Compare the spatiotemporal distribution (cervicovaginal, rectal, systemic), explant tissue anti-HIV effect, toxicological assessment, and acceptability of the 0528/tenofovir candidate gel formulation for vaginal and rectal dosing in an exploratory pre-Phase I clinical study.

Public Health Relevance

These studies will provide critical data to assess the combination 0528/tenofovir vaginal and rectal gel using antiviral effect, safety, pharmacokinetics, and acceptability measurements. These data domains will enable rational decision making regarding further pursuit of this novel ARV combination which includes an active agent (0528) not currently licensed for use in HIV treatment and suitable for both vaginal and rectal use.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI101961-03
Application #
8699500
Study Section
Special Emphasis Panel (ZAI1-ESB-A)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$731,203
Indirect Cost
$98,106
Name
Imquest Biosciences
Department
Type
DUNS #
146051664
City
Frederick
State
MD
Country
United States
Zip Code
21704