PURPOSE: to experimentally evaluate the diabetogenic effects of antiretroviral drugs on pregnant Wistar rats and the perinatal effects on the offspring. METHODS: adult female pregnant Wistar rats weighing 200-230 g were used. The antiretroviral drugs zidovudine (ZDV), lamivudine (3TC) and nelfinavir (NFV) were used alone and in association at daily doses of ten times the dose normally used in pregnant women, proportionally to the animal's body weight. Seven groups were studied, including the control. The experiment started on day 0 of pregnancy and the pregnant animals were sacrificed on day 21. The fetuses were counted and weighed. Blood determinations of glucose, insulin, glucagon and lactate were performed on day 21. The retroperitoneal adipose tissue was weighed. Data were analyzed statistically by Student's t-test. RESULTS: the groups treated with 3TC, ZDV + 3TC and ZDV + 3TC + NFV showed decreasing values of maternal daily body weight gain, retroperitoneal adipose tissue weight and weight of fetuses (control group: 6.2 g; 3TC group variation: 4.1-5.6 g). The serum lactate levels were also decreased when compared to the control in these groups (control group: 5.8 mmol/mL; 3TC group variations: 3.2-3.7 mmol/mL). All antiretroviral-treated groups showed a decreasing number of fetuses when compared to the control (control group: 14.7; drug group variation: 11.1-12.7). All treated groups also showed decreasing serum values of insulin (control group: 6.2 µIU/mL; drug group variation: 2.1 to 2.7 µIU/mL) and increasing serum levels of glucagon when compared to the control (control group: 88.2 pg/mL; drug group variation: 99.7 to 120.7 pg/mL). There was no statistical significance of glucose levels when comparing treated groups to the control. CONCLUSIONS: the antiretroviral drugs interfered in carbohydrate metabolism of pregnant rats and reduced the number of fetuses. 3TC caused less maternal body weight gain, decreased fetus weight and lactate and insulin levels and increased serum glucagon.
Antiretroviral drugs; Diabetes mellitus; HIV and pregnancy; Pregnancy outcome
