Fetal and maternal outcome after administration of tenofovir to gravid rhesus monkeys (Macaca mulatta)

Alice F Tarantal, Alesha Castillo, Jason E. Ekert, Norbert Bischofberger, R. Bruce Martin

Research output: Contribution to journalArticle

79 Scopus citations

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 ∼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 ≤ .03); 2) a significant reduction in circulating IGF-I (p < .001); 3) a small reduction in fetal bone porosity (p ≤ .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.

Original languageEnglish (US)
Pages (from-to)207-220
Number of pages14
JournalJournal of Acquired Immune Deficiency Syndromes
Volume29
Issue number3
StatePublished - Mar 1 2002

Keywords

  • Bone
  • Fetus
  • IGF
  • Monkey
  • Pregnancy
  • Tenofovir

ASJC Scopus subject areas

  • Virology
  • Immunology

Fingerprint Dive into the research topics of 'Fetal and maternal outcome after administration of tenofovir to gravid rhesus monkeys (Macaca mulatta)'. Together they form a unique fingerprint.

  • Cite this