title: A summary of preclinical topical microbicide vaginal safety and chlamydial efficacy evaluations in a pigtailed macaque model.
abstract: BACKGROUND
  The development of topical microbicides represents a new and exciting field in the prevention of sexually transmitted diseases, and it is especially important that candidate products undergo rigorous preclinical safety and efficacy testing before advancing to clinical trials.
  
  
  METHODS
  We have developed a standardized protocol for preclinical vaginal safety and efficacy assessment of topical microbicide candidates in a nonhuman primate model. Over 7 years of funding under an NIH contract, we evaluated a total of 28 test compounds for vaginal safety (via colposcopy, vaginal pH, and microflora) and 9 compounds for efficacy against cervical chlamydial infection. 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 cervicovaginal environment. We also outline the specific criteria used to determine which products should move into efficacy trials and which should be recommended for reformulation to the manufacturer.
  
  
  RESULTS
  Overall, we noted acceptable safety profiles for 24 of 28 candidate products. Common findings included a transient decrease in vaginal pH, petechiae, and mild erythema. Four products were associated with significant adverse colposcopic findings including blisters, epithelial abrasions, and friability; all 4 products were successfully reformulated and showed acceptable safety profiles at lower concentrations. No products showed complete protection against cervical chlamydial infection.
  
  
  CONCLUSIONS
  The macaque preclinical safety and efficacy model is critical to maintaining the pace of topical microbicide development, which could ultimately offer a significant opportunity for intervention in the global HIV/AIDS epidemic.
authors.affiliation: Department of Obstetrics and Gynecology, Box 356460, University of Washington, Seattle, WA 98195-6460, USA. dpatton@u.washington.edu
authors.forename: Dorothy L
authors.initials: DL
authors.lastname: Patton
authors.forename: Yvonne T
authors.initials: YT
authors.lastname: Cosgrove Sweeney
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Paul
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D002689:Chlamydia / Q000187:drug effects*; D002690:Chlamydia Infections / Q000188:drug therapy* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D008254:Macaca nemestrina; D012749:Sexually Transmitted Diseases / Q000188:drug therapy / Q000517:prevention & control; D016896:Treatment Outcome; D014621:Vagina / Q000187:drug effects*
chemical_list: D000891:Anti-Infective Agents, Local