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NNRTI Gel Shows Safety as a Topical Anti-HIV Microbicide in Animal Tests
 
 
  By Martha Kerr
 
NEW YORK (Reuters Health) Jun 12 - Macaques given an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) gel called UC781 in repeated vaginal and rectal applications exhibited no evidence of systemic absorption, researchers report.
 
Dr. D. L. Patton of the University of Washington in Seattle and colleagues administered rectal and vaginal applications of two different concentrations of UC781, 1.0% and 0.1%, to pig-tailed macaques. Results of their study are published in the May issue of Antimicrobial Agents and Chemotherapy.
 
Using liquid chromatography, the investigators saw no systemic absorption on repeated applications of either formulation of the microbicide. However, UC781 was detectable on cervicovaginal lavage up to six hours after application.
 
Vaginal applications of UC781 appeared safe on colposcopy and in assessments of vaginal cytokine levels and microflora.
 
In contrast, rectal applications of the 1.0% formulation were accompanied by increases in a number of cytokines. Application of the 0.1% concentration was not. "The clinical significance of this finding remains unknown," Dr. Patton told Reuters Health.
 
"UC781 may be localizing in some as yet unidentified cellular compartment," the Seattle investigator acknowledged. "It is possible that any UC781 that may have been absorbed into the systemic circulation, may have localized in the blood cells, and thus would not have been detected in our analytical analyses. We are currently developing an analytical method appropriate for detection of UC781 in blood cells in order to explore this possibility."
 
The researchers say their findings support continued research with UC781 as a topical anti-HIV microbicide.
 
"A new research grant through the U19 Co-Operative agreement funding mechanism sponsored by the NIH is currently under peer review. Continued grant support would allow our research team to further explore the feasibility of UC781 as a topical microbicide," Dr. Patton said.
 
Antimicrob Agents Chemother 2007;51:1608-1615
 
 
 
 
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