title: 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.affiliation: Center for Biomedical Research, Population Council, New York, New York, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kenney
authors.forename: Aixa
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Larisa
authors.initials: L
authors.lastname: Kizima
authors.forename: Samantha
authors.initials: S
authors.lastname: Seidor
authors.forename: Radhika
authors.initials: R
authors.lastname: Menon
authors.forename: Ninochka
authors.initials: N
authors.lastname: Jean-Pierre
authors.forename: Pavel
authors.initials: P
authors.lastname: Pugach
authors.forename: Keith
authors.initials: K
authors.lastname: Levendosky
authors.forename: Nina
authors.initials: N
authors.lastname: Derby
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Gabriela
authors.initials: G
authors.lastname: Paglini
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Zydowsky
authors.forename: Melissa
authors.initials: M
authors.lastname: Robbiani
authors.forename: José A
authors.initials: JA
authors.lastname: Fernández Romero
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D018938:Caco-2 Cells; D002176:Candida albicans / Q000187:drug effects; D002351:Carrageenan / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D005782:Gels / Q000008:administration & dosage*; D006678:HIV / Q000472:pathogenicity; D015658:HIV Infections / Q000188:drug therapy; D006561:Herpes Simplex / Q000188:drug therapy*; D018258:Herpesvirus 2, Human / Q000472:pathogenicity; D006801:Humans; D007778:Lactobacillus / Q000187:drug effects; D008253:Macaca mulatta; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D009994:Osmolar Concentration; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D014709:Vero Cells; D019345:Zinc Acetate / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000998:Antiviral Agents; D005782:Gels; D002351:Carrageenan; D019345:Zinc Acetate