Kenney Jessica, Singer Rachel, Derby Nina, Aravantinou Meropi, Abraham Ciby J, Menon Radhika, Seidor Samantha, Zhang Shimin, Gettie Agegnehu, Blanchard James, Piatak Michael, Lifson Jeffrey D, Fernández-Romero José A, Zydowsky Thomas M, Robbiani Melissa
Population Council , New York, New York, USA.
AIDS Res Hum Retroviruses. 2012 Nov;28(11):1476-84. doi: 10.1089/aid.2012.0087. Epub 2012 Jul 30.
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.
此前我们发现,反复经阴道应用MIV-150/醋酸锌角叉菜胶(MIV-150/ZA/CG)凝胶和醋酸锌角叉菜胶(ZA/CG)凝胶可显著保护猕猴免受阴道猿猴人类免疫缺陷病毒逆转录酶(SHIV-RT)感染。凝胶的应用方式为每日1次,共2周,或隔日1次,共4周,在用药4 - 24小时后对动物进行病毒攻击。在此,我们研究了在病毒攻击前或攻击后单次经阴道给药的效果。受MIV-150/ZA/CG经阴道给药所呈现的保护作用鼓舞,我们还对其进行了直肠给药测试。在阴道攻击前8 - 24小时、攻击后1小时或攻击前24小时及攻击后1小时,分别经阴道应用1次MIV-150/ZA/CG、ZA/CG和CG凝胶。在直肠攻击前8小时或24小时,经直肠应用1次MIV-150/ZA/CG和CG凝胶。虽然在阴道攻击前及攻击前/后应用MIV-150/ZA/CG凝胶可提供显著保护(88%,p<0.002),但仅在攻击后应用则无显著保护作用。ZA/CG凝胶在攻击前可降低感染率,但不显著,且在攻击后这种作用完全消失。在攻击前8 - 24小时经直肠应用MIV-150/ZA/CG凝胶,对直肠攻击的保护作用有限。因此,MIV-150/ZA/CG凝胶是一种高效的阴道杀菌剂,可提供24小时的阴道感染防护,并且在接近HIV暴露时给药可能对直肠感染有效。