Stavudine effects on rat pregnancy outcome

Objective: Stavudine is an inhibitor of HIV reverse transcriptase and acts as a chain terminator during DNA synthesis. The aim of the study presented here was to evaluate the effects of stavudine during rat pregnancy. Methods: Female rats were randomly divided into four treatment groups: GI (treated with the drug vehicle); GII; GIII; and GIV (treated with 1, 3 or 9 mg/kg of stavudine, respectively) (n = 25 pregnant rats for every group). Rats were treated by gavage once daily. The treatment period extended from day 0 until the 20th day of pregnancy. Body weights were recorded weekly during this period. At term, the rats were sacrificed, and the implantation sites and number of fetuses and resorptions were recorded. The fetuses were evaluated for external abnormalities under a stereomicroscope. Results: No differences in body weight gain between the groups were observed. The mean number of implantations per dam in stavudine-treated groups was higher than in the control group (P < 0.05); however, only GIII presented an increase in the mean number of resorptions compared to the other groups (P < 0.01). The resorption/implantation rate was higher in the GII group and lower in the GIV group as compared to the other groups. Neither the mean fetal weights nor the placental weights differed significantly among the groups. No external anomalies were observed at dissection in rat fetuses, placentae or uteri. Conclusion: Rat pregnancy outcome seems to be affected by stavudine, mainly with respect to the mechanisms of intrauterine concept survival.