title: MIV-150/zinc acetate gel inhibits cell-associated simian-human immunodeficiency virus reverse transcriptase infection in a macaque vaginal explant model.
abstract: The transmission of both cell-free and cell-associated immunodeficiency viruses has been demonstrated directly in multiple animal species and possibly occurs in humans, as suggested by genotyping of the infecting human immunodeficiency virus (HIV) in acutely infected women and in semen from their partners. Therefore, a microbicide may need to block both mechanisms of HIV transmission to achieve maximum efficacy. To date, most of the preclinical evaluation of candidate microbicides has been performed using cell-free HIV. New models of mucosal transmission of cell-associated HIV are needed to evaluate candidate microbicide performance. The MIV-150/zinc acetate/carrageenan (MZC) gel protects Depo-Provera-treated macaques against cell-free simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection when applied vaginally up to 8 h before challenge. We recently demonstrated the potent activity of MZC gel against cell-free SHIV-RT in macaque vaginal explants. In the current study, we established a cell-associated SHIV-RT infection model of macaque vaginal tissues and tested the activity of MZC gel in this model. MZC gel protected tissues against cell-associated SHIV-RT infection when present at the time of viral exposure or when applied up to 4 days prior to viral challenge. These data support clinical testing of the MZC gel. Overall, our ex vivo model of cell-associated SHIV-RT infection in macaque vaginal mucosa complements the cell-free infection models, providing tools for prioritization of products that block both modes of HIV transmission.
authors: Population Council, New York, New York, USA.
authors: Patrick
authors: P
authors: Barnable
authors: Population Council, New York, New York, USA.
authors: Giulia
authors: G
authors: Calenda
authors: Population Council, New York, New York, USA.
authors: Thierry
authors: T
authors: Bonnaire
authors: Population Council, New York, New York, USA.
authors: Radhika
authors: R
authors: Menon
authors: Population Council, New York, New York, USA.
authors: Keith
authors: K
authors: Levendosky
authors: Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York, USA.
authors: Agegnehu
authors: A
authors: Gettie
authors: Tulane National Primate Research Center, Tulane University, Covington, Louisiana, USA.
authors: James
authors: J
authors: Blanchard
authors: Population Council, New York, New York, USA.
authors: Michael L
authors: ML
authors: Cooney
authors: Population Council, New York, New York, USA.
authors: José A
authors: JA
authors: Fernández-Romero
authors: Population Council, New York, New York, USA.
authors: Thomas M
authors: TM
authors: Zydowsky
authors: Population Council, New York, New York, USA nteleshova@popcouncil.org.
authors: Natalia
authors: N
authors: Teleshova
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D002584:Cervix Uteri / Q000821:virology; D005260:Female; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D008253:Macaca mulatta; D008992:Monkey Diseases / Q000188:drug therapy / Q000821:virology; D009092:Mucous Membrane / Q000821:virology; D011725:Pyridines / Q000627:therapeutic use*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000635:transmission; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D014508:Urea / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014622:Vaginal Creams, Foams, and Jellies / Q000627:therapeutic use; D019345:Zinc Acetate / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; C510296:MIV 150; D011725:Pyridines; D014622:Vaginal Creams, Foams, and Jellies; D014508:Urea; D054303:HIV Reverse Transcriptase; D019345:Zinc Acetate