title: Tenofovir disoproxil fumarate intravaginal ring protects high-dose depot medroxyprogesterone acetate-treated macaques from multiple SHIV exposures.
abstract: Preclinical HIV prevention models use either a single high-dose viral challenge in depot medroxyprogesterone acetate-treated macaques or repeated viral challenges in cycling macaques. We tested the efficacy of an intravaginal tenofovir disoproxil fumarate (TDF) ring in a model combining repeated 30-mg injections of depot medroxyprogesterone acetate every 6 weeks with vaginal viral challenges weekly for 12 weeks. Twelve macaques were randomized to TDF or placebo rings. All placebo macaques became infected after a median of 2 exposures, whereas only 1 TDF macaque became infected at the eighth exposure (P = 0.0012). The TDF ring provides durable protection in a stringent challenge model.
authors.affiliation: *Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA; †Department of Biomedical Engineering, Northwestern University Evanston, Evanston, IL; ‡Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY; §Total Solutions, Inc, Atlanta, GA; and ‖Department of Pediatrics and Microbiology-Immunology, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: James M
authors.initials: JM
authors.lastname: Smith
authors.forename: Priya
authors.initials: P
authors.lastname: Srinivasan
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Teller
authors.forename: Yungtai
authors.initials: Y
authors.lastname: Lo
authors.forename: Chuong T
authors.initials: CT
authors.lastname: Dinh
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Kiser
authors.forename: Betsy C
authors.initials: BC
authors.lastname: Herold
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D008254:Macaca nemestrina; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage*; D010757:Phosphorous Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control* / Q000635:transmission; D014621:Vagina
chemical_list: C574165:9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine; D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D010757:Phosphorous Acids; D010919:Placebos; D017258:Medroxyprogesterone Acetate; D000225:Adenine