Microbicide safety/efficacy studies in animals: macaques and small animal models
- PMID: 19373023
- PMCID: PMC2694621
- DOI: 10.1097/COH.0b013e32830891bb
Microbicide safety/efficacy studies in animals: macaques and small animal models
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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References
-
- Moore JP, Shattock RJ. Preventing HIV-1 sexual transmission--not sexy enough science, or no benefit to the bottom line? J Antimicrob Chemother. 2003 Dec;52(6):890–2. - PubMed
-
- Turpin JA. Considerations and development of topical microbicides to inhibit the sexual transmission of HIV. Expert Opin Investig Drugs. 2002;11(8):1077–97. - PubMed
-
- Hillier SL, Moench T, Shattock R, Black R, Reichelderfer P, Veronese F. In vitro and in vivo: the story of nonoxynol 9. J Acquir Immune Defic Syndr. 2005 May 1;39(1):1–8. - PubMed
-
- Patton DL, Cosgrove Sweeney YT, Rabe LK, Hillier SL. Rectal applications of nonoxynol-9 cause tissue disruption in a monkey model. Sex Transm Dis. 2002 Oct;29(10):581–7. - PubMed
-
- Galen BT, Martin AP, Hazrati E, Garin A, Guzman E, Wilson SS, et al. A comprehensive murine model to evaluate topical vaginal microbicides: mucosal inflammation and susceptibility to genital herpes as surrogate markers of safety. J Infect Dis. 2007 May 1;195(9):1332–9. - PubMed
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