title: An intravaginal ring that releases the NNRTI MIV-150 reduces SHIV transmission in macaques.
abstract: Microbicides may prevent HIV and sexually transmitted infections (STIs) in women; however, determining the optimal means of delivery of active pharmaceutical ingredients remains a major challenge. We previously demonstrated that a vaginal gel containing the non-nucleoside reverse transcriptase inhibitor MIV-150 partially protected macaques from SHIV-RT (simian/HIV reverse transcriptase) infection, and the addition of zinc acetate rendered the gel significantly protective. We test the activity of MIV-150 without the addition of zinc acetate when delivered from either ethylene vinyl acetate (EVA) or silicone intravaginal rings (IVRs). MIV-150 was successfully delivered, because it was detected in vaginal fluids and tissues by radioimmunoassay in pharmacokinetic studies. Moreover, EVA IVRs significantly protected macaques from SHIV-RT infection. Our results demonstrate that MIV-150-containing IVRs have the potential to prevent HIV infection and highlight the possible use of IVRs for delivering drugs that block HIV and other STIs.
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Singer
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Mawson
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Derby
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: Aixa
authors.initials: A
authors.lastname: Rodriguez
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: Larisa
authors.initials: L
authors.lastname: Kizima
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: Radhika
authors.initials: R
authors.lastname: Menon
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Goldman
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kenney
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: Meropi
authors.initials: M
authors.lastname: Aravantinou
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Seidor
authors.affiliation: Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY 10065, USA.
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.affiliation: Tulane National Primate Research Center, Tulane University, Covington, LA 70433, USA.
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.affiliation: AIDS and Cancer Virus Program, SAIC-Frederick, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.affiliation: AIDS and Cancer Virus Program, SAIC-Frederick, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: José A
authors.initials: JA
authors.lastname: Fernández-Romero
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Robbiani
authors.affiliation: Center for Biomedical Research, Population Council, New York, NY 10065, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Zydowsky
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D003274:Contraceptive Devices, Female; D005260:Female; D020128:Inhibitory Concentration 50; D008251:Macaca / Q000821:virology*; D009705:Nucleosides / Q000494:pharmacology*; D011145:Polyvinyls / Q000737:chemistry; D011725:Pyridines / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012828:Silicones / Q000737:chemistry; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control* / Q000635:transmission*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C510296:MIV 150; D009705:Nucleosides; D011145:Polyvinyls; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D012828:Silicones; C016438:ethylenevinylacetate copolymer; D014508:Urea