title: Animal models for microbicide safety and efficacy testing.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USA. rveazey@tulane.edu
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology* / Q000633:toxicity*; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000633:toxicity*; D004195:Disease Models, Animal; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D004353:Drug Evaluation, Preclinical; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D008253:Macaca mulatta; D012107:Research Design; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000517:prevention & control
chemical_list: D000891:Anti-Infective Agents, Local; D044966:Anti-Retroviral Agents