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. 2008 Sep;3(5):567-73.
doi: 10.1097/COH.0b013e32830891bb.

Microbicide safety/efficacy studies in animals: macaques and small animal models

Affiliations

Microbicide safety/efficacy studies in animals: macaques and small animal models

Ronald S Veazey. Curr Opin HIV AIDS. 2008 Sep.

Abstract

Purpose of review: A number of microbicide candidates have failed to prevent HIV transmission in human clinical trials, and there is uncertainty as to how many additional trials can be supported by the field. Regardless, there are far too many microbicide candidates in development, and a logical and consistent method for screening and selecting candidates for human clinical trials is desperately needed. The unique host and cell specificity of HIV, however, provides challenges for microbicide safety and efficacy screening, that can only be addressed by rigorous testing in relevant laboratory animal models.

Recent findings: A number of laboratory animal model systems ranging from rodents to nonhuman primates, and single versus multiple dose challenges have recently been developed to test microbicide candidates. These models have shed light on both the safety and efficacy of candidate microbicides as well as the early mechanisms involved in transmission. This article summarizes the major advantages and disadvantages of the relevant animal models for microbicide safety and efficacy testing.

Summary: Currently, nonhuman primates are the only relevant and effective laboratory model for screening microbicide candidates. Given the consistent failures of prior strategies, it is now clear that rigorous safety and efficacy testing in nonhuman primates should be a prerequisite for advancing additional microbicide candidates to human clinical trials.

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Figures

Figure 1
Figure 1
Comparative histology of the vaginal mucosa of a human (A) and rhesus macaque (B). Note the similarities in the thickness and the arrangement of the the squamous epithelium. Vaginal biopsies were obtained from a normal woman in the luteal phase of the menstrual cycle prior to initiating a study to examine the effects of progestins on the vaginal epithelium (45) and from a normal rhesus macaque in the luteal phase.
Figure 2
Figure 2
Comparative histology of the vaginal mucosa from the same woman in the luteal (A) and follicular (B) stages of the menstrual cycle. Note that during the luteal phase (menses) there are areas of thinning in the vaginal mucosa where he epithelium is only a few cell layers thick. Photomicrograph C is from a woman with subclinical (asymptomatic) inflammation characterized by numerous infiltrates of inflammatory cells penetrating the squamous epithelium. Such conditions (thinning or inflammation of the vaginal epithelium) may increase vaginal HIV transmission rates. All biopsies were obtained from normal asymptomatic women prior to initiating a study to examine the effects of progestins on the vaginal epithelium (45).
Figure 3
Figure 3
Macaque species most commonly used in microbicides research including the rhesus macaque (A), pigtailed macaque (B) and cynomolgus macaque (C).

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