Fetal and Maternal Outcome After Administration of Tenofovir to Gravid Rhesus Monkeys (Macaca mulatta)
作者:
Alice Tarantal,
Alesha Castillo,
Jason Ekert,
Norbert Bischofberger,
R. Martin,
期刊:
JAIDS Journal of Acquired Immune Deficiency Syndromes
(OVID Available online 2002)
卷期:
Volume 29,
issue 3
页码: 207-220
ISSN:1525-4135
年代: 2002
出版商: OVID
关键词: Fetus;Pregnancy;Monkey;Bone;IGF;Tenofovir
数据来源: OVID
摘要:
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.
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