A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV
Prevalent infection with human herpes simplex 2 (HSV-2) or human papillomavirus (HPV) is associated with increased human immunodeficiency virus (HIV) acquisition. Microbicides that target HIV as well as these sexually transmitted infections (STIs) may more effectively limit HIV incidence. Previously, we showed that a microbicide gel (MZC) containing MIV-150, zinc acetate (ZA) and carrageenan (CG) protected macaques against simian-human immunodeficiency virus (SHIVRT) infection and that a ZC gel protected mice against HSV-2 infection. Here we evaluated a modified MZC gel (containing different buffers, co-solvents, and preservatives suitable for clinical testing) against both vaginal and rectal challenge of animals with SHIV-RT, HSV-2 or HPV. MZC was stable and safe in vitro (cell viability and monolayer integrity) and in vivo (histology). MZC protected macaques against vaginal (p,0.0001) SHIV-RT infection when applied up to 8 hours (h) prior to challenge. When used close to the time of challenge, MZC prevented rectal SHIV-RT infection of macaques similar to the CG control. MZC significantly reduced vaginal (p < 0.0001) and anorectal (p = 0.0187) infection of mice when 106 pfu HSV-2 were applied immediately after vaginal challenge and also when 5 × 103 pfu were applied between 8 h before and 4 h after vaginal challenge (p < 0.0248). Protection of mice against 86106 HPV16 pseudovirus particles (HPV16 PsV) was significant for MZC applied up to 24 h before and 2 h after vaginal challenge (p < 0.0001) and also if applied 2 h before or after anorectal challenge (p < 0.0006). MZC provides a durable window of protection against vaginal infection with these three viruses and, against HSV-2 and HPV making it an excellent candidate microbicide for clinical use.
Kizima, Larisa, Aixa Rodriguez, Jessica Kenney, Nina Derby, Olga Mizenina, Radhika Menon, Samantha Seidor, Shimin Zhang, Keith Levendosky, Ninochka Jean-Pierre, Pavel Pugach, Guillermo Villegas, Brian E. Ford, Agegnehu Gettie, James F. Blanchard, Michael Piatak Jr., Jeffrey D. Lifson, Maria Gabriela Paglini, Natalia Teleshova, Thomas Zydowsky, Melissa Robbiani, and José Fernández-Romero. 2014. "A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV," PLoS ONE 9(4): e94547.
Developing an ARV-Based Microbicide Gel