title: Two low doses of tenofovir protect newborn macaques against oral simian immunodeficiency virus infection.
abstract: Simple affordable interventions are needed to reduce vertical human immunodeficiency virus (HIV) transmission in developing countries. The efficacy of 2 low doses (4 mg/kg, subcutaneously) or 1 high dose (30 mg/kg, subcutaneously) of the reverse-transcriptase inhibitor 9-[2-(phosphonomethoxy)propyl]adenine (PMPA; tenofovir) to protect newborn macaques against simian immunodeficiency virus (SIV) infection was investigated. Thirteen newborn macaques were inoculated orally with virulent SIVmac251. The 4 placebo-treated animals (group A) became persistently infected. Groups B and C (n=4 in each group) received 2 4-mg/kg doses of PMPA, either 4 h before and 20 h after (group B) or 1 and 25 h after SIV inoculation (group C). One animal (group D) received a single 30-mg/kg dose of PMPA 1 h after SIV inoculation. Despite evidence of an initial transient infection, 3 group B animals, 2 group C animals, and the group D animal were SIV negative and seronegative at ages 19-23 months. Immune activation with recall antigens or pharmacologic immunosuppression with corticosteroids failed to reactivate viral replication. These data suggest that 1 or 2 doses of PMPA may protect human newborns against intrapartum HIV infection.
authors.affiliation: California Regional Primate Research Center, University of California, Davis, CA 95616-8542, USA. kkvanrompay@ucdavis.edu
authors.forename: K K
authors.initials: KK
authors.lastname: Van Rompay
authors.forename: M B
authors.initials: MB
authors.lastname: McChesney
authors.forename: N L
authors.initials: NL
authors.lastname: Aguirre
authors.forename: K A
authors.initials: KA
authors.lastname: Schmidt
authors.forename: N
authors.initials: N
authors.lastname: Bischofberger
authors.forename: M L
authors.initials: ML
authors.lastname: Marthas
mesh_terms: D000225:Adenine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000914:Antibodies, Viral / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D006801:Humans; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D011533:Proviruses; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity / Q000502:physiology; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D000914:Antibodies, Viral; D004279:DNA, Viral; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine