Background: According to a recent publication, there is insufficient information to assess the human teratogenic risk for the majority of drugs introduced in the U.S. in the last 20 years. The objective of this paper is to examine the human teratogenic risk of the HIV protease inhibitor VIRACEPT (nelfinavir mesylate), which was introduced in the U.S. in 1997.

Methods: This study uses a subset of the data from the Antiretroviral Pregnancy Registry (APR), which is designed to monitor prenatal exposures to antiretroviral therapy and detect a potential increase in the risk of birth defects. The APR uses a prospective exposure-registration cohort design in which healthcare providers register pregnant women with prenatal exposures to any antiretroviral therapy, report data on exposure throughout pregnancy, and provide birth outcome data. For this study, all pregnancies exposed to nelfinavir, used alone or in combination, were extracted from APR and analyzed. The prevalence of birth defects is compared to the CDC’s population-based surveillance system. Statistical inference is based on exact methods for binomial proportions. For all defects combined, a cohort of 200 is required to detect a doubling of risk compared to CDC’s expected prevalence, with 80% power and a Type I error rate of 5%. For specific defects, the power varies with the frequency of the defect in the population and the size of the exposed group.

Results: Through January 2002, the APR has monitored 757 live births exposed to nelfinavir. Among 256 first trimester exposures, there were 8 birth defects, for a prevalence of 3.1% (95% CI = 1.4, 6.1). This rate is not significantly different from the CDC’s system with a prevalence of 3.1 per 100 live births (95% CI = 3.1, 3.2). There is no consistent pattern among reported birth defects.

Conclusions: While few drugs introduced in the U.S. in the last 20 yrs have sufficient information to assess human teratogenic risk, for nelfinavir, sufficient numbers of first trimester exposures have been monitored to detect a 2-fold increase in the risk of overall birth defects. No such increase has been detected. The numbers are not sufficient to detect the risk of specific defects. While nelfinavir should only be used in pregnant women if the benefits outweigh the potential risk to the fetus, the findings from this study should provide some assurance. APR is ongoing; exposures to all antiretroviral therapies during pregnancy may be reported by calling 800-258-4263.