TY - JOUR
T1 - Quantitative assessment of altered rectal mucosal permeability due to rectally applied nonoxynol-9, biopsy, and simulated intercourse
AU - Fuchs, Edward J.
AU - Grohskopf, Lisa A.
AU - Lee, Linda A.
AU - Bakshi, Rahul P.
AU - Hendrix, Craig W.
N1 - Funding Information:
Financial support. This work was supported by the Centers for Disease Control and HIV Prevention (contract 200-2001-08015) and the National Institutes of Health National Center for Research Resources (grant M01-RR000052 to the Johns Hopkins General Clinical Research Center). Potential conflicts of interest. All authors: No reported conflicts.
PY - 2013/5/1
Y1 - 2013/5/1
N2 - 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.
AB - 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.
KW - HIV rectal microbicide
KW - Nonoxynol-9
KW - epithelial disruption
KW - mucosal permeability
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U2 - 10.1093/infdis/jit030
DO - 10.1093/infdis/jit030
M3 - Article
C2 - 23325915
AN - SCOPUS:84875971126
SN - 0022-1899
VL - 207
SP - 1389
EP - 1396
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 9
ER -