title: A MIV-150/zinc acetate gel inhibits SHIV-RT infection in macaque vaginal explants.
abstract: To extend our observations that single or repeated application of a gel containing the NNRTI MIV-150 (M) and zinc acetate dihydrate (ZA) in carrageenan (CG) (MZC) inhibits vaginal transmission of simian/human immunodeficiency virus (SHIV)-RT in macaques, we evaluated safety and anti-SHIV-RT activity of MZC and related gel formulations ex vivo in macaque mucosal explants. In addition, safety was further evaluated in human ectocervical explants. The gels did not induce mucosal toxicity. A single ex vivo exposure to diluted MZC (1∶30, 1∶100) and MC (1∶30, the only dilution tested), but not to ZC gel, up to 4 days prior to viral challenge, significantly inhibited SHIV-RT infection in macaque vaginal mucosa. MZC's activity was not affected by seminal plasma. The antiviral activity of unformulated MIV-150 was not enhanced in the presence of ZA, suggesting that the antiviral activity of MZC was mediated predominantly by MIV-150. In vivo administration of MZC and CG significantly inhibited ex vivo SHIV-RT infection (51-62% inhibition relative to baselines) of vaginal (but not cervical) mucosa collected 24 h post last gel exposure, indicating barrier effect of CG. Although the inhibitory effect of MZC (65-74%) did not significantly differ from CG (32-45%), it was within the range of protection (∼75%) against vaginal SHIV-RT challenge 24 h after gel dosing. Overall, the data suggest that evaluation of candidate microbicides in macaque explants can inform macaque efficacy and clinical studies design. The data support advancing MZC gel for clinical evaluation.
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Barnable
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Giulia
authors.initials: G
authors.lastname: Calenda
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Louise
authors.initials: L
authors.lastname: Ouattara
authors.affiliation: Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York, United States of America.
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.affiliation: Tulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Ninochka
authors.initials: N
authors.lastname: Jean-Pierre
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Larisa
authors.initials: L
authors.lastname: Kizima
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Aixa
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Ciby
authors.initials: C
authors.lastname: Abraham
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Radhika
authors.initials: R
authors.lastname: Menon
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Samantha
authors.initials: S
authors.lastname: Seidor
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cooney
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Roberts
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Sperling
authors.affiliation: AIDS and Cancer Virus Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.affiliation: AIDS and Cancer Virus Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Fernandez-Romero
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Zydowsky
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Robbiani
authors.affiliation: Population Council, New York, New York, United States of America.
authors.forename: Natalia
authors.initials: N
authors.lastname: Teleshova
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002351:Carrageenan / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D005260:Female; D005782:Gels / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000187:drug effects / Q000821:virology; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000235:genetics; D046509:Tissue Culture Techniques; D014508:Urea / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D014621:Vagina / Q000187:drug effects* / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects; D019345:Zinc Acetate / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D019380:Anti-HIV Agents; D005782:Gels; C510296:MIV 150; D011725:Pyridines; D014508:Urea; D002351:Carrageenan; D019345:Zinc Acetate