This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Recently, serious liver toxicity and rash have been reported with nevirapine (NVP), and anti-HIV drug, in HIV-1 infected pregnant women. The relationship between the blood levels of NVP and its metabolites and the risk of liver toxicity has not been investigated. In this study using baboons as a model, we will determine if high blood levels of NVP and its metabolites may increase the risk of liver toxicity in the mother and the fetus during pregnancy. A total of 18 pregnant baboons will be equally divided into three treatment groups: group 1 will not receive NVP (control) group 2 will receive NVP at 5 mg/kg twice a day, and group 3 will receive NVP at 10 mg/kg twice a day. Nevirapine will be administered starting at day 70 gestational age. Four blood samples and a small piece of liver from the mother will be collected at 2nd and 3rd trimesters, and four weeks following delivery. A small amount of cord blood will be collected from the fetus at 2nd and 3rd trimesters. One sample each of maternal blood, cord blood, and amniotic fluid will be collected at delivery. All newborn baboons will be sacrificed following delivery and a piece of the newborn liver will be collected and reviewed under the microscope for evidence of liver damage.Currently, NVP is commonly used in the treatment o HVI infection in pregnant women. The results from the proposed study will determine if high blood levels of NVP or its metabolites may increase the risks of liver injuries in the mother and fetus following in utero exposure. The data generated will provide the needed information to establish safer dosages for NVP use during pregnancy and to improve maternal and neonatal outcomes.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR013986-10
Application #
7716068
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2008-05-01
Project End
2009-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
10
Fiscal Year
2008
Total Cost
$21,315
Indirect Cost
Name
Texas Biomedical Research Institute
Department
Type
DUNS #
007936834
City
San Antonio
State
TX
Country
United States
Zip Code
78245
Shelton, Elaine L; Waleh, Nahid; Plosa, Erin J et al. (2018) Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data. Pediatr Res 84:458-465
Perminov, Ekaterina; Mangosing, Sara; Confer, Alexandra et al. (2018) A case report of ovotesticular disorder of sex development (OT-DSD) in a baboon (Papio spp.) and a brief review of the non-human primate literature. J Med Primatol 47:192-197
Jensen, Jeffrey T; Hanna, Carol; Mishler, Emily et al. (2018) Effect of menstrual cycle phase and hormonal treatments on evaluation of tubal patency in baboons. J Med Primatol 47:40-45
Confer, Alexandra; Owston, Michael A; Kumar, Shyamesh et al. (2018) Multiple endocrine neoplasia-like syndrome in 24 baboons (Papio spp.). J Med Primatol 47:434-439
Mustonen, Allison; Gonzalez, Olga; Mendoza, Elda et al. (2018) Uremic encephalopathy in a rhesus macaque (Macaca mulatta): A case report and a brief review of the veterinary literature. J Med Primatol :
Koistinen, Keith; Mullaney, Lisa; Bell, Todd et al. (2018) Coccidioidomycosis in Nonhuman Primates: Pathologic and Clinical Findings. Vet Pathol 55:905-915
Mahaney, Michael C; Karere, Genesio M; Rainwater, David L et al. (2018) Diet-induced early-stage atherosclerosis in baboons: Lipoproteins, atherogenesis, and arterial compliance. J Med Primatol 47:3-17
Mangosing, Sara; Perminov, Ekaterina; Gonzalez, Olga et al. (2018) Uterine Tumors Resembling Ovarian Sex Cord Tumors in Four Baboons ( Papio spp.). Vet Pathol 55:753-758
Joganic, Jessica L; Willmore, Katherine E; Richtsmeier, Joan T et al. (2018) Additive genetic variation in the craniofacial skeleton of baboons (genus Papio) and its relationship to body and cranial size. Am J Phys Anthropol 165:269-285
Kumar, Shyamesh; Laurence, Hannah; Owston, Michael A et al. (2017) Natural pathology of the captive chimpanzee (Pan troglodytes): A 35-year review. J Med Primatol 46:271-290

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