Population Council Research that makes a difference

18th Conference on Retroviruses
and Opportunistic Infections (CROI)
27 February–2 March 2011

Abstract

"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

Background
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.

Methods
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.

Results
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.

Conclusions
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.

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