TOXICITY OF ANTI-HIV DRUGS IN PRE- &POSTNATAL MACAQUES

Project: Research project

Project Details

Description

The overall aim of these studies is to design and utilize a fetal/neonatal
macaque model for the evaluation of the potential toxicities of various
anti-HIV drug treatment(s) proposed for use in the human pediatric patient.
Our long-term objectives will be (1) to devise methods for assessing
potential pre- and postnatal toxicities during exposure to anti-HIV drug
therapies, (2) to evaluate various drug treatment and administration
periods for testing the potential toxicities of various anti-HIV drugs, (3)
to determine the effects of pre- and postnatal anti-HIV treatment
strategies on normative growth and development, specifically related to
neurobehavioral, hematologic, and physiologic parameters, and (4) to
correlate adverse effects with drug levels achieved in the maternal, fetal,
and neonatal/infant compartments. One of the greatest challenges with new
anti-HIV therapies will be to determine the route of administration and
dosages to be used. Within Specific Aim 1, we will establish methods for
treating the drug(s) under scrutiny. Drug administration via the maternal
(oral or intravenous [IV]), fetal ("oral" via amniotic fluid,
intraperitoneal, or IV), and neonatal/infant (oral, IV) routes will be
evaluated using AZT as a prototype drug. In addition to monitoring for
toxicity, these studies will provide information on drug levels achieved in
various maternal (serum, urine), fetal (amniotic fluid, serum,
cerebrospinal fluid [CSF]), and neonatal (serum, urine, CSF) compartments.
The information gained from these studies will be applied to further
evaluations of the potential toxic and adverse effects of prenatal and pre-
and postnatal treatment of various anti-HIV drugs by monitoring growth and
neurobehavioral development (Specific Aim 2) and hematologic effects while
monitoring drug levels achieved in various maternal, fetal, and
neonatal/infant compartments (Specific Aim 3). Both treatment periods
(prenatal [gestational day (GD) 60-160] and pre-and postnatal [GD 60-160
and daily for 6 months]) will be pursued since it is currently unknown if
pre- and postnatal treatment alone will prove sufficient to alter
transmission of the virus or the course of infection. It will be important
to identify the spectrum of adverse effects that may be related to this
lengthy exposure period. With the studies outlined above we will be able
to compare the differing routes of drug administration (maternal versus
fetal) in addition to a varying length of drug exposure (prenatal versus
pre- and postnatal). It is our goal to evaluate the optimal methods for
drug delivery while minimizing toxic or adverse effects, and to determine
the potential ramifications or various drug treatment strategies on pre-and
postnatal individuals.
StatusFinished
Effective start/end date9/30/917/31/98

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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