Effects of combined zidovudine/lopinavir/ritonavir therapy during rat pregnancy: morphological aspects.

PURPOSE: To evaluate the morphological aspects in rats subjected to an association of the antiretroviral drugs zidovudine/lopinavir/ritonavir in different doses administered throughout the gestational period.

MATERIALS AND

METHODS

Forty pregnant rats were randomly allocated into four groups: control (Ctrl) and experimental (Exp1, Exp2, and Exp3), which received zidovudine/lopinavir/ritonavir in the doses of 10/13.3/3.3, 30/39.9/9.9, and 90/119.7/29.7 mg/kg per day from the first to the 20th day of pregnancy, respectively. At term, the animals were euthanized and maternal and fetal organ samples were removed for morphological analysis.

RESULTS

No major changes were identified in the group treated with the lowest dosing compared with the control. In group Exp2, the authors found hepatocytes with eosinophilic cytoplasm, pyknotic nuclei, and vasodilation. The proximal convoluted tubules of maternal kidneys showed eosinophilic areas and hyperchromatic nuclei, as well as signs of vasodilation. In the group treated with the highest dose (Exp3); the morphological changes in the maternal kidneys and livers were similar and more pronounced than those found in Exp2. The maternal pancreas of groups Exp2 and Exp3 evidenced moderate and progressive signs of tissue damage. The morphological features of all fetal livers, kidneys, and pancreases were normal.

CONCLUSION

High doses of zidovudine/lopinavir/ritonavir association during the entire rat pregnancy period can cause definite morphological changes in maternal liver, kidneys, and pancreas. On the other hand, the corresponding fetal organs were not affected.