Quantitative assessment of altered rectal mucosal permeability due to rectally applied nonoxynol-9, biopsy, and simulated intercourse

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Microbicide toxicity may reduce the efficacy of topical preexposure prophylaxis for human immunodeficiency virus (HIV) transmission. Noninvasive quantitative measures of microbicide toxicity would usefully inform microbicide development.Methods. Ten subjects received 3 one-time interventions: 5 mL of Normosol-R fluid alone (negative control), 5 mL of 2% nonoxynol-9 (N-9) gel, and 5 mL of Normosol-R with coital simulation and sigmoidoscopic biopsy (CS + BX). Each dose of N-9 and Normosol-R contained 500 micro Ci of 99mtechnetium-diethylene triamine pentaacetic acid. Plasma and urine radioactivity was assessed over 24 hours.Results. The plasma radioisotope concentration peaked 1 hour after N-9 dosing. The mean maximum radioisotope concentration after N-9 receipt was 12.0 times (95% confidence interval [CI], 6.8-21.0) and 8.4 times (95% CI, 5.2-13.5) the mean concentration after Normosol-R control receipt and CS + BX receipt, respectively; paired differences persisted for 24 hours. After N-9 dosing, the urine isotope level was 3.6 times (95% CI, 1.1-11.4) the level observed 8 hours after Normosol-R control receipt and 4.0 times (95% CI, 1.4-11.4) the level observed 4 hours after CS + BX receipt. Permeability after CS + BX receipt was greater than that after Normosol-R control receipt in 0-2-hour urine specimens only (mean permeability, 2.4; 95% CI, 1.0-5.8) but was not greater in blood.Conclusions. Plasma sampling after rectal radioisotope administration provided quantitative estimates of altered mucosal permeability after chemical and mechanical stresses. Permeability testing may provide a useful noninvasive adjunct to assess the mucosal effects of candidate microbicides.

Original languageEnglish (US)
Pages (from-to)1389-1396
Number of pages8
JournalJournal of Infectious Diseases
Volume207
Issue number9
DOIs
StatePublished - May 1 2013

Keywords

  • HIV rectal microbicide
  • Nonoxynol-9
  • epithelial disruption
  • mucosal permeability

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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