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 Citations (Scopus)

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

Fingerprint

Tenofovir
Macaca mulatta
Mothers
Bone and Bones
Biomarkers
Fetus
Hysterotomy
Multifetal Pregnancy Reduction
Body Weight
Crown-Rump Length
Pregnancy
Simian Immunodeficiency Virus
Clinical Chemistry
Porosity
Somatomedins
Fetal Development
Viral Load
Fetal Blood
Insulin-Like Growth Factor I
Placenta

Keywords

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

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Fetal and maternal outcome after administration of tenofovir to gravid rhesus monkeys (Macaca mulatta). / Tarantal, Alice F; Castillo, Alesha; Ekert, Jason E.; Bischofberger, Norbert; Martin, R. Bruce.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 29, No. 3, 01.03.2002, p. 207-220.

Research output: Contribution to journalArticle

Tarantal, Alice F ; Castillo, Alesha ; Ekert, Jason E. ; Bischofberger, Norbert ; Martin, R. Bruce. / Fetal and maternal outcome after administration of tenofovir to gravid rhesus monkeys (Macaca mulatta). In: Journal of Acquired Immune Deficiency Syndromes. 2002 ; Vol. 29, No. 3. pp. 207-220.
@article{01a71680bea54516b07f78c5dc63920e,
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 ∼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.",
keywords = "Bone, Fetus, IGF, Monkey, Pregnancy, Tenofovir",
author = "Tarantal, {Alice F} and Alesha Castillo and Ekert, {Jason E.} and Norbert Bischofberger and Martin, {R. Bruce}",
year = "2002",
month = "3",
day = "1",
language = "English (US)",
volume = "29",
pages = "207--220",
journal = "Journal of acquired immune deficiency syndromes (1999)",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Fetal and maternal outcome after administration of tenofovir to gravid rhesus monkeys (Macaca mulatta)

AU - Tarantal, Alice F

AU - Castillo, Alesha

AU - Ekert, Jason E.

AU - Bischofberger, Norbert

AU - Martin, R. Bruce

PY - 2002/3/1

Y1 - 2002/3/1

N2 - 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.

AB - 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.

KW - Bone

KW - Fetus

KW - IGF

KW - Monkey

KW - Pregnancy

KW - Tenofovir

UR - http://www.scopus.com/inward/record.url?scp=0036500034&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036500034&partnerID=8YFLogxK

M3 - Article

C2 - 11873070

AN - SCOPUS:0036500034

VL - 29

SP - 207

EP - 220

JO - Journal of acquired immune deficiency syndromes (1999)

JF - Journal of acquired immune deficiency syndromes (1999)

SN - 1525-4135

IS - 3

ER -