A modified zinc acetate gel, a potential nonantiretroviral microbicide, is safe and effective against simian-human immunodeficiency virus and herpes simplex virus 2 infection in vivo.

Abstract

We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. In vitro toxicity to lactobacilli and Candida albicans was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (P = 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (P < 0.0001) and rectal (P = 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2.

• Authors: Jessica Kenney, Aixa Rodríguez, Larisa Kizima, Samantha Seidor, Radhika Menon, Ninochka Jean-Pierre, Pavel Pugach, Keith Levendosky, Nina Derby, Agegnehu Gettie, James Blanchard, Michael Piatak Jr, Jeffrey D Lifson, Gabriela Paglini, Thomas M Zydowsky, Melissa Robbiani, José A Fernández Romero
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 57 Issue 8 Pg. 4001-9 (Aug 2013) ISSN: 1098-6596 [Electronic] United States
• PMID: 23752515 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Anti-Bacterial Agents
• Antifungal Agents
• Antiviral Agents
• Gels
• Carrageenan
• Zinc Acetate

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Antifungal Agents (pharmacology)
• Antiviral Agents (pharmacology)
• Caco-2 Cells
• Candida albicans (drug effects)
• Carrageenan (pharmacology)
• Chlorocebus aethiops
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Female
• Gels (administration & dosage)
• HIV (pathogenicity)
• HIV Infections (drug therapy)
• Herpes Simplex (drug therapy)
• Herpesvirus 2, Human (pathogenicity)
• Humans
• Lactobacillus (drug effects)
• Macaca mulatta
• Mice
• Microbial Sensitivity Tests
• Microbial Viability (drug effects)
• Osmolar Concentration
• Simian Acquired Immunodeficiency Syndrome (drug therapy)
• Simian Immunodeficiency Virus (pathogenicity)
• Vero Cells
• Zinc Acetate (administration & dosage, pharmacology)