A single dose of a MIV-150/Zinc acetate gel provides 24 h of protection against vaginal simian human immunodeficiency virus reverse transcriptase infection, with more limited protection rectally 8-24 h after gel use.

Abstract

Previously we showed that repeated vaginal application of a MIV-150/zinc acetate carrageenan (MIV-150/ZA/CG) gel and a zinc acetate carrageenan (ZA/CG) gel significantly protected macaques from vaginal simian human immunodeficiency virus reverse transcriptase (SHIV-RT) infection. Gels were applied either daily for 2 weeks or every other day for 4 weeks, and the animals were challenged 4-24 h later. Herein, we examined the effects of a single vaginal dose administered either before or after virus challenge. Encouraged by the vaginal protection seen with MIV-150/ZA/CG, we also tested it rectally. Vaginal applications of MIV-150/ZA/CG, ZA/CG, and CG gel were performed once 8-24 h before, 1 h after, or 24 h before and 1 h after vaginal challenge. Rectal applications of MIV-150/ZA/CG and CG gel were performed once 8 or 24 h before rectal challenge. While vaginal pre-challenge and pre/post-challenge application of MIV-150/ZA/CG gel offered significant protection (88%, p<0.002), post-challenge application alone did not significantly protect. ZA/CG gel reduced infection prechallenge, but not significantly, and the effect was completely lost post-challenge. Rectal application of MIV-150/ZA/CG gel afforded limited protection against rectal challenge when applied 8-24 h before challenge. Thus, MIV-150/ZA/CG gel is a highly effective vaginal microbicide that demonstrates 24 h of protection from vaginal infection and may demonstrate efficacy against rectal infection when given close to the time of HIV exposure.

• Authors: Jessica Kenney, Rachel Singer, Nina Derby, Meropi Aravantinou, Ciby J Abraham, Radhika Menon, Samantha Seidor, Shimin Zhang, Agegnehu Gettie, James Blanchard, Michael Piatak Jr, Jeffrey D Lifson, José A Fernández-Romero, Thomas M Zydowsky, Melissa Robbiani
• Journal: AIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 28 Issue 11 Pg. 1476-84 (Nov 2012) ISSN: 1931-8405 [Electronic] United States
• PMID: 22737981 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Infective Agents
• MIV 150
• Pyridines
• Vaginal Creams, Foams, and Jellies
• Urea
• RNA-Directed DNA Polymerase
• Zinc Acetate

Topics

• Administration, Intravaginal
• Administration, Rectal
• Animals
• Anti-Infective Agents (pharmacokinetics, pharmacology)
• Female
• Herpes Genitalis (drug therapy, pathology, prevention & control)
• Herpesvirus 2, Human (drug effects)
• Humans
• Pyridines (pharmacokinetics, pharmacology)
• RNA-Directed DNA Polymerase (drug effects)
• Rectum (pathology, virology)
• Simian Acquired Immunodeficiency Syndrome (drug therapy, pathology, prevention & control)
• Simian Immunodeficiency Virus (drug effects)
• Time Factors
• Treatment Outcome
• Urea (analogs & derivatives, pharmacokinetics, pharmacology)
• Vagina (pathology, virology)
• Vaginal Creams, Foams, and Jellies
• Zinc Acetate (pharmacokinetics, pharmacology)