A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide is Safe and Effective Against SHIV-RT and HSV-2 infection In Vivo

KENNEY J.; RODRÍGUEZ A.; KIZIMA L.; SEIDOR S.; MENON R.; JEAN-PIERRE N.; PUGACH P.; LEVENDOSKY K.; GETTIE A.; BLANCHARD J.; PIATAK JR. M.; LIFSON J.D.; PAGLINI G.; ZYDOWSKY T.; ROBBIANI M.; FERNÁNDEZ ROMERO J.A.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2013 vol. 57 p. 4001 - 4009

0066-4804

Background: We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal HSV-2 challenge, as well as macaques against vaginal SHIV-RT challenge. In this work we optimized buffers and co-solvents to obtain a stable, iso-osmolar formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. Methods: In vitro toxicity to Lactobacillus and Candida albicans was estimated. Macaques were given daily doses of ZA/CG or CG vaginally for 14d and challenged with SHIV-RT 24h later. Mice were challenged vaginally or rectally with HSV-2 after a single gel treatment to measure efficacy or 12h after daily gel treatment for 7d to evaluate the gel?s impact on susceptibility to HSV-2 infection. Results: Optimized ZA/CG neither decreased the viability of Lactobacillus or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 53% when macaques were challenged 24h after the last dose of gel. We observed 60-80% survival of mice against vaginal (p