title: Assessing the risk of birth defects associated with exposure to highly active anti-retroviral therapy during organogenesis in rats.
abstract: The use of anti-retroviral drugs during pregnancy has increased since the demonstration of reduction of mother-to-child transmission of HIV with highly active antiretroviral therapy (HAART). The risk of HAART cannot be ruled out; data are generally limited or varied. This study intends to thoroughly assess the teratogenic effect of HAART on the organogenesis stage of fetal development using animal model. Pregnant rats were divided into 13 groups with 12 animals per group. The therapeutic doses of drug administration were done to simulate the treatment pattern in APIN HIV/AIDS Clinic of the University of Lagos Teaching Hospital, Nigeria (find detailed treatment groups in methodology). Six rats in each group were randomly selected and sacrificed on day 20 by cervical dislocation prior to day 21 of gestation and the foetuses were harvested through abdominal incision for physical examination. Blood samples were collected from the 1st filial rats of the remaining six animals for biochemical and haematological examination. The liver, kidney, heart and brain of all the sacrificed animals were used for histopathological examination. There were significant (P ≤ 0.05) low birth weights of the foetuses of the animals that were treated with HAART. Results also revealed a reduction (P ≤ 0.05) in the platelets counts, WBC and RBC of most treatment groups at the first filial generation. Significant (P ≤ 0.05) elevations in the levels of AST and UA in the foetuses of the animals treated with HAART were also observed. It can be concluded that administration of single and combined antiretrovirals have potential teratogenic effect.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Lagos, PMB 12003, Lagos-Nigeria. awodeleo@gmail.com
authors.forename: Olufunsho
authors.initials: O
authors.lastname: Awodele
authors.forename: Daniel
authors.initials: D
authors.lastname: Popoola
authors.forename: Paul
authors.initials: P
authors.lastname: Odunsi
authors.forename: Ralph
authors.initials: R
authors.lastname: Akinde
authors.forename: Alade
authors.initials: A
authors.lastname: Akintonwa
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D011247:Pregnancy; D051381:Rats; D000014:Abnormalities, Drug-Induced / Q000209:etiology; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D001772:Blood Cell Count; D000013:Congenital Abnormalities / Q000209:etiology; D047109:Fetal Development / Q000187:drug effects; D008431:Maternal-Fetal Exchange; D023421:Models, Animal; D038081:Organogenesis / Q000187:drug effects; D011919:Rats, Inbred Strains; D012306:Risk; D000831:Animals, Newborn; D001724:Birth Weight