A Summary of Preclinical Topical Microbicide Rectal Safety... : Sexually Transmitted Diseases (original) (raw)

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A Summary of Preclinical Topical Microbicide Rectal Safety and Efficacy Evaluations in a Pigtailed Macaque Model

Patton, Dorothy L. PHD; Sweeney, Yvonne T. Cosgrove BA; Paul, Kathleen J. MPH

From the Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington

Supported by grants P01-AI-39061, U19 AI 051661, U19 AI 060598, and Washington National Primate Research Center RR00166. The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the Division of AIDS.

Correspondence: Dorothy L. Patton, PhD, Department of Obstetrics and Gynecology, Box 356460, University of Washington, Seattle, WA 98195-6460. E-mail: [email protected].

Received for publication July 31, 2008, and accepted Nov 17, 2008.

Background:

There is widespread recognition of the potential promise of vaginal microbicides as a tool to combat global human immunodeficiency virus/acquired immunodeficiency syndrome and sexually transmitted infections epidemics, and candidate product development has maintained a rapid pace in recent years; however, rectal microbicide development has received less attention. As it is likely that commercial products developed for vaginal use will also be used rectally, there is a clear need to assess the safety and efficacy of candidate microbicide products specifically in the rectal compartment.

Methods:

We have developed a standardized protocol for preclinical rectal safety and (chlamydial) efficacy assessment of topical microbicide candidates in a nonhuman primate model. We evaluated a total of 12 test compounds for rectal safety (via rectal pH, microflora, and rectal lavage) and 1 compound for efficacy against rectal chlamydial infection.

Results:

In this article, we describe our methods in detail and summarize our results, particularly noting the ability of our model to distinguish products with deleterious effects on the rectal environment. We also outline the specific criteria used to recommend products move into preclinical rectal efficacy trials or be recommended for reformulation to the product developer. In summary, we observed significant adverse effects in 2 products. The single product that underwent efficacy evaluation was not observed to be protective against rectal chlamydial infection.

Conclusions:

A preclinical safety and efficacy model is critical to promoting rectal microbicide development, which will ultimately offer a significant opportunity for intervention in the global HIV/AIDS epidemic.