18th Conference on Retroviruses
and Opportunistic Infections (CROI)
27 February–2 March 2011
"A single application of a MIV-150/zinc acetate combination gel provides macaques 24h of protection against vaginal infection with SHIV-RT"
Jessica Kenney, Meropi Aravantinou, Nina Derby, Jeffrey D. Lifson, Michael Piatak Jr., Jose Fernández-Romero, Thomas M. Zydowsky, Agegnehu Gettie, James Blanchard, Melissa Robbiani
Microbicides that block HIV and other STIs, like HSV-2, are needed to more effectively limit HIV transmission. Zinc acetate in carrageenan exhibits potent anti-HSV-2 activity in mice. We recently found that a gel combining 50mM MIV-150 (a NNRTI) with 14mM zinc acetate dihydrate in carrageenan completely protected macaques against vaginal challenge with SHIV-RT when applied daily for 2 weeks prior to challenge 24h after the last application. Herein, we reported the efficacy of this MIV-150/zinc acetate gel when applied once 24h before, once 1h after, or both 24h before and 1h after virus challenge.
Depo-Provera–treated macaques (n=27) had the test gel or the carrageenan control gel applied vaginally 24h pre-, 1h post-, or both 24h pre- and 1h post- (n=7 per test, n=2 per control group) vaginal challenge with 103 TCID50 SHIV-RT. Infection was determined by nested PCR for SIV gag DNA in PBMCs in conjunction with Cx-1 co-culture with PBMCs data. Statistical significance was determined with Fisher's exact test.
None of the animals receiving test gel 24h before challenge became infected (0/7, 0%) while 2/7 animals receiving test gel 1h post-challenge (28.6%) and 1/7 receiving test gel 24h pre- and 1h post-challenge became infected (14.3%). In contrast, 1/2 animals (50%) in each of the corresponding control groups became infected (3/6 in total). Statistical analyses were done using control data pooled with historical carrageenan-treated controls (n=20; 9/14 infected in prior studies vs. 3/6 infected herein). With the inclusion of historical controls (12/20 infected), the protection afforded by application of the MIV-150/zinc acetate gel 24h before challenge was significant (p<0.009). The reduced infection frequency in animals treated with the gel both pre- and post-challenge did not reach significance (p<0.08), probably due to the small number of animals tested. Post-exposure treatment appeared to afford limited protection.
The MIV-150/zinc acetate gel protects macaques against vaginal challenge with SHIV-RT for up to 24h after single or repeated dosing. Based on these findings, this microbicide gel has the potential to be used in a coitally independent manner to limit HIV and potentially HSV-2 infection and warrants further testing in humans.
Return to: Guide to Population Council activities
Offsite link: CROI Web site
firstname.lastname@example.org; +1 212 339 0509
Contacts and Resources
For 60 years, the Population Council has changed the way the world thinks about important health and development issues. Explore an interactive timeline of the Council's history, learn more about some of our key contributions, and watch a short video about why your support is so important to us.