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Department of Pediatrics, Children's Hospital at Albany Medical Center, Albany, New York
On behalf of all of the authors of "Pharmacokinetics and Safety of Stavudine in HIV-Infected Pregnant Women and Their Infants: Pediatric AIDS Clinical Trials Group Protocol 332" [1], I would like to respond to Blanche's correspondence [2] by pointing out that our study was a phase 1 study and, as such, was designed to preliminarily address the pharmacokinetics and safety of stavudine (d4T) during pregnancy. Thus, we agree that, as a phase 1 study, it did not address the issue of safety in large numbers of women and infants, and we did not imply that it did. Also, we did not conclude that d4T is safe but rather that it was well tolerated by all of the pregnant women in our study who received it. The laboratory toxicities seen in the infants were fully described, and the roles played by in utero exposure to d4T and/or lamivudine or by neonatal exposure to zidovudine were discussed as probable causes of the toxicities; in these infants, the toxicities resolved without requiring treatment. The infants received only single doses of d4T at weeks 1 and 6. We did not describe d4T as being well tolerated by the infants; rather, we pointed out the observed toxicities and noted that they may have been secondary to in utero drug exposure. The study was not designed to assess mitochondrial toxicity in this small number of infants; however, the issue of the potential mitochondrial toxicity of d4T was included in the Discussion, and we concluded that d4T should be used with caution during pregnancy, especially if combined with didanosine. It is clear that additional studies with larger numbers of pregnant women are necessary to fully understand the safety profile of d4T in pregnant women and their infants and that long-term follow-up of infants exposed in utero to antiretroviral drugs is required to assess any late adverse outcomes of such exposure.
References
1. Wade NA, Unadkat JD, Huang S, et al. Pharmacokinetics and safety of stavudine in HIV-infected pregnant women and their infants: Pediatric AIDS Clinical Trials Group Protocol 332. J Infect Dis 2004; 190:216774. First citation in article
2. Blanche S. Safety of stavudine during pregnancy . J Infect Dis 2005; 191:15678 (in this issue). First citation in article