Stavudine is an anti-AIDS drug that is widely used in some countries to prevent HIV transmission from a pregnant woman to her foetus. However, a dose-dependent effect of Stavudine on early neurogenesis was demonstrated by mouse embryotoxicity studies. Exposure to Stavudine reduced the number of somites, yolk sac diameter and crown-rump length, and increased the rate of embryonic degeneration compared to controls. At the molecular level, it caused DNA damage, increased levels of phosphorylated-CHK1 and cleaved-Caspase-3, and decreased levels of nuclear antigen expression in proliferating cells. These changes suggest that Stavudine elicits a coordinated DNA damage response in embryos, inhibits cell proliferation and induces apoptosis. All of the above suggest that exposure to Stavudine interferes with embryonic development.

Earlier studies have also demonstrated that high doses of Stavudine can cause mild to moderate maternal hepatotoxicity and pancreatic toxicity at the morphological level in pregnant rats. However, there was no concomitant change in biochemical parameters, which is likely due to the functional reserve of these organs. In addition, Stavudine causes changes in maternal body weight, which has a detrimental effect on foetal weight. In summary, Stavudine is unlikely to be suitable for use in pregnant patients, but must be taken under medical supervision if required.

References:

[1] RUI-FANG AO . Stavudine exposure results in developmental abnormalities by causing DNA damage, inhibiting cell proliferation and inducing apoptosis in mouse embryos[J]. Toxicology, 2020. DOI:10.1016/j.tox.2020.152443.

[2] M U NAKAMURA. Effect of six antiretroviral drugs (delavirdine, stavudine, lamivudine, nelfinavir, amprenavir and lopinavir/ritonavir in association) on albino pregnant rats (Rattus norvegicus Albinus, Rodentia, Mammalia): biological assay.[J]. Ceska Gynekologie-Czech Gynaecology, 2014.

[3] REGINA LúCIA BRAGA BARRETO . Effects of chronic stavudine exposure on liver, pancreas and kidneys of pregnant rats and their fetuses: Morphological and biochemical aspects[J]. European journal of obstetrics, gynecology, and reproductive biology, 2006. DOI:10.1016/j.ejogrb.2005.12.027.