title: Fetal and maternal outcome after administration of tenofovir to gravid rhesus monkeys (Macaca mulatta).
abstract: Tenofovir has been shown to cross the placenta in quantities sufficient to sustain reductions in viral load in simian immunodeficiency virus (SIV)-infected fetal monkeys. With chronic exposure (30 mg/kg), however, significant bone-related toxicity has been shown in approximately 25% of infants studied. Further investigations were conducted to determine whether the bone-related toxicity observed was initiated during fetal life. Gravid rhesus monkeys (n = 4) were administered tenofovir subcutaneously once daily from 20 to 150 days of gestation (30 mg/kg; term: 165 +/- 10 days). Fetuses were monitored sonographically, and maternal and fetal blood and urine samples were collected to assess hematologic parameters, clinical chemistry, insulin-like growth factor (IGF) levels, and bone biomarkers. Fetuses were delivered by hysterotomy near term for necropsy and evaluation of bone-related mechanical properties. Results of these studies have shown 1) normal fetal development, although overall body weights and crown-rump lengths were less than those for age-matched controls (p < or = .03); 2) a significant reduction in circulating IGF-I (p <.001); 3) a small reduction in fetal bone porosity (p < or = .03); and 4) transient alterations in maternal body weights and bone-related biomarkers during the treatment period. The results of these studies suggest that chronic fetal exposure to tenofovir at the maternal dose of 30 mg/kg throughout gestation can alter select fetal parameters and transiently affect maternal bone biomarkers.
authors.affiliation: California Regional Primate Research Center, University of California at Davis, 95616-8542, USA. aftarantal@primate.ucdavis.edu
authors.forename: Alice F
authors.initials: AF
authors.lastname: Tarantal
authors.forename: Alesha
authors.initials: A
authors.lastname: Castillo
authors.forename: Jason E
authors.initials: JE
authors.lastname: Ekert
authors.forename: Norbert
authors.initials: N
authors.lastname: Bischofberger
authors.forename: R Bruce
authors.initials: RB
authors.lastname: Martin
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000633:toxicity*; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D001835:Body Weight; D001842:Bone and Bones / Q000187:drug effects* / Q000196:embryology / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D020073:Gravidity; D008253:Macaca mulatta / Q000196:embryology / Q000502:physiology*; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D011247:Pregnancy; D011256:Pregnancy Outcome; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D013002:Somatomedins / Q000032:analysis; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D018894:Reverse Transcriptase Inhibitors; D013002:Somatomedins; D000068698:Tenofovir; D000225:Adenine