O10.6 A Potent Combination Microbicide Gel Inhibits SHIV-RT, HSV-2 and HPV Infectionsin Vivo

Background HIV acquisition is fueled by infection with HSV-2 and HPV. Microbicides that target all three STIs may more effectively limit HIV incidence. We previously showed that a gel containing the NNRTI MIV-150, zinc acetate (Z) and carrageenan (C, MZC) significantly protected macaques from vaginal SHIV-RT challenge, while ZC also protected mice against HSV-2 vaginally and rectally. Here we evaluate a new formulation of MZC optimised for clinical use against SHIV-RT, HSV-2, and HPV. Methods Toxicity was measured using the HSV-2 increased susceptibility model in mice. Macaques received gels vaginally every day for 14d followed by SHIV-RT (10 3 TCID 50 ) 8 or 24h post-last gel or SHIV-RT plus HSV-2 (2 × 10 8 pfu) 8h post-last gel. Rectally, gels were applied 1h before SHIV-RT. Anti-HSV-2 and anti-HPV16 PsV activities were assessed by vaginally or rectally challenging mice with different viral doses 24h before to 8h after single gel application. Significance was determined by Fisher’s exact or Mann Whitney U tests (P Results MZC pretreatment did not enhance HSV-2 infection of mice. MZC protected macaques against vaginal SHIV-RT infection (in the presence or absence of HSV-2) for up to 8h (p Conclusion MZC provides a durable window of protection against SHIV-RT, HSV-2, and HPV in vivo , making MZC an excellent candidate microbicide for clinical use.