title: Evaluation of oral tenofovir disoproxil fumarate and topical tenofovir GS-7340 to protect infant macaques against repeated oral challenges with virulent simian immunodeficiency virus.
abstract: Simian immunodeficiency virus (SIV) infection of infant macaques is a useful animal model of pediatric HIV infection to evaluate the potential of chemoprophylactic regimens to reduce mother-to-infant transmission of HIV. Previous studies have demonstrated that short-term subcutaneous administration of the reverse transcriptase inhibitor tenofovir was highly effective in protecting newborn macaques against infection after a single high-dose oral inoculation with virulent SIVmac251. In the current study, we mimicked HIV transmission through breast-feeding by repeatedly feeding infant macaques low doses of SIVmac251. Topical administration of a low dose of the second-generation tenofovir prodrug GS-7340 did not have detectable prophylactic efficacy. Oral administration of tenofovir disoproxil fumarate (DF; 10 mg/kg SID) lowered the infection rate at birth, but had lower efficacy against virus infection at 4 weeks of age, most likely because drug levels became suboptimal relative to those obtained with the current tenofovir DF regimen in humans. These prophylactic results further underscore the relevance of the current tenofovir DF prevention trials in pediatric and adult populations.
authors.affiliation: California National Primate Research Center, University of California, Davis, CA 95616-8542, USA. kkvanrompay@ucdavis.edu
authors.forename: Koen K A
authors.initials: KK
authors.lastname: Van Rompay
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kearney
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Sexton
authors.forename: Roxana
authors.initials: R
authors.lastname: Colón
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lawson
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Blackwood
authors.forename: William A
authors.initials: WA
authors.lastname: Lee
authors.forename: Norbert
authors.initials: N
authors.lastname: Bischofberger
authors.forename: Marta L
authors.initials: ML
authors.lastname: Marthas
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000284:Administration, Oral; D000287:Administration, Topical; D000409:Alanine; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D020022:Genetic Predisposition to Disease; D008253:Macaca mulatta; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D011355:Prodrugs / Q000008:administration & dosage / Q000627:therapeutic use; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000472:pathogenicity*; D000068698:Tenofovir / Q000031:analogs & derivatives; D014774:Virulence
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D011355:Prodrugs; D000068698:Tenofovir; C442442:tenofovir alafenamide; D000225:Adenine; D000409:Alanine