In vitro assays used to evaluate the ability of a microbicide to prevent HIV transmission typically utilize models more relevant to the development of anti-HIV therapeutic agents and quantify virus production at short time intervals following infection (3-6 days) using insensitive methodology. To mitigate the shortcomings of these critical biological assays, we have developed a microbicide transmission and sterilization assay (MTSA) to more sensitively and quantitatively evaluate virus transmission in cell culture in the presence of microbicidal compounds. The MTSA defines the concentration of the microbicide required to totally suppress the transmission, replication, and spread of virus in cell culture and may thus help define the effective concentration of the microbicide required to be present in target cells upon delivery in a formulated microbicide product. In light of the difficulty of quantifying the dose of a microbicide product that is required for the delivery of an effective product, it is important to understand how in vitro methodology, complemented with appropriate ex vivo and in vivo pharmacokinetic and pharmacodynamics evaluations, might inform the development process and serve to better define appropriate dosing strategies. Among microbicide developers, the dosing problem is now addressed through the philosophy of

Public Health Relevance

Research performed in this Project will allow microbicide developers to determine the dose of a microbicide product that is required in their formulated product such that the formulated product will deliver the required quantity of drug to the target tissue in the vagina and rectum to totally suppress the transmission of HIV-1. The in vitro surrogate assay will allow rapid prioritization of microbicide compounds for clinical development.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-ESB-A)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Imquest Biosciences
United States
Zip Code
Weld, Ethel D; Hiruy, Hiwot; Guthrie, Kate Morrow et al. (2017) A Comparative Pre-Phase I Study of the Impact of Gel Vehicle Volume on Distal Colon Distribution, User Experience, and Acceptability. AIDS Res Hum Retroviruses 33:440-447
Ham, Anthony S; Buckheit Jr, Robert W (2017) Designing and developing suppository formulations for anti-HIV drug delivery. Ther Deliv 8:805-817
Gao, Y; Yuan, A; Chuchuen, O et al. (2015) Vaginal deployment and tenofovir delivery by microbicide gels. Drug Deliv Transl Res 5:279-94
Ham, Anthony S; Nugent, Sean T; Peters, Jennifer J et al. (2015) The rational design and development of a dual chamber vaginal/rectal microbicide gel formulation for HIV prevention. Antiviral Res 120:153-64
Katz, David F; Yuan, Andrew; Gao, Yajing (2015) Vaginal drug distribution modeling. Adv Drug Deliv Rev 92:2-13
Pereira, Lara E; Mesquita, Pedro M M; Ham, Anthony et al. (2015) Pharmacokinetic and Pharmacodynamic Evaluation following Vaginal Application of IQB3002, a Dual-Chamber Microbicide Gel Containing the Nonnucleoside Reverse Transcriptase Inhibitor IQP-0528 in Rhesus Macaques. Antimicrob Agents Chemother 60:1393-400