Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USA.
Curr Opin HIV AIDS. 2013 Jul;8(4):295-303. doi: 10.1097/COH.0b013e328361d096.
Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates.
Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials.
Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.
综述目的：早期研究对动物模型预测 HIV 预防策略成败的实用性提出了质疑，但多项人类 3 期杀微生物剂试验的结果，以及对人类和动物模型试验之间差异的探讨，表明动物模型能够预测杀微生物候选物的安全性和有效性。
最近的发现：最近的研究表明，局部应用阴道凝胶和使用单一或联合抗逆转录病毒的口服预防措施确实能有效预防人类的性传播 HIV，所有这些成功都在动物模型中得到了预测。此外，动物和人类研究结果之间以前的差异终于被揭开，这是由于模型设计中的研究设计不足，或者在人类试验中经常出现不遵守规定的情况，后者越来越被认为是人类杀微生物剂试验中的一个主要问题。
总结：人类中成功的杀微生物剂研究验证了动物模型中的结果，目前正在进行几项研究，以进一步调查这些候选物在动物和非人类灵长类动物模型中的组织分布、疗效持续时间以及重复应用的持续安全性等问题，同时还在研究其他有前途的杀微生物候选物。既然我们最终与预防策略和 HIV 传播保护有了积极的关联，我们就可以回顾性地验证动物模型预测这些结果的能力，更重要的是，前瞻性地使用这些模型来选择和推进更安全、更有效、更重要的是更持久的杀微生物候选物进入人体试验。
