Title:Current Concepts for the IND-Directed Development of Microbicide Products to Prevent the Sexual Transmission of HIV
Volume: 16
Issue: 10
Author(s): Karen W. Buckheit, Christian Furlan-Freguia, Anthony S. Ham and Robert W. Buckheit
Affiliation:
Keywords:
Topical microbicide, HIV-1, Preclinical development, Pharmacodynamics, Pharmacokinetics, Toxicity, Prevention.
Abstract: In the absence of an approved and effective vaccine, topical microbicides have become the
strategy of choice to provide women with the ability to prevent the sexual transmission of HIV. Topical
microbicides are chemical and physical agents specifically developed and formulated for use in either
the vaginal or rectal environment to prevent the sexual transmission of infectious organisms. Although
a microbicide product will have many of the same properties as other anti-infective therapeutic
agents, the microbicide development pathway has significant differences which reflect the complex
biological environment in which the products must act. These challenges to the development of an effective
microbicide are reflected in the recently released FDA Guidance document which defines the
microbicide development algorithm and includes the evaluation of preclinical efficacy and toxicity, and safety and toxicology,
and indicates the necessity of testing of the active pharmaceutical product as well as an optimal formulation for
delivery of the microbicide product. The microbicide development algorithm requires evaluation of the potential microbicidal
agent and final formulated product in assays which mimic the microenvironment of the vagina and rectum during the
sexual transmission of HIV, including the evaluation of activity and cytotoxicity in the appropriate biological matrices,
toxicity testing against normal vaginal flora and at standard vaginal pH, testing in ectocervical and colorectal explant tissue,
and irritation studies to vaginal, rectal and penile tissue. Herein, we discuss currently accepted practices required for
the development of a successful microbicide product which will prevent virus transmission in the vaginal and rectal
vaults.
