Pharmacokinetic (PK) changes during pregnancy can reduce serum levels of many protease inhibitors, posing a risk of virologic failure. The optimal dosages of several protease inhibitors for pregnant women are not known. A recent study evaluated the PK parameters as well as the efficacy and safety of two dosages of ritonavir-boosted atazanavir (ATV/r) in pregnant women.
Women in the second and third trimesters of pregnancy were treated with ATV/r at the standard dosage of 300/100 mg once daily (n = 20) or at a higher dosage of 400/100 mg once daily (n = 21); all were also given zidovudine + lamivudine. PK data were compared with historical results from studies of nonpregnant adults (presumably mostly men). During the third trimester, the mean ATV AUC was 21% lower in women who received ATV/r 300/100 mg than in nonpregnant adults, and the mean Cmax was 27% lower. However, the mean Cmin was equivalent to that in nonpregnant adults. In women who received ATV/r 400/100 mg, the mean AUC and Cmax and were virtually the same as those in nonpregnant adults, but the mean Cmin was 39% higher. Bilirubin elevations were more common in women on the higher dosage of ATV, and in their infants (though the bilirubin levels in the infants appeared to decrease sharply in the first 2 weeks of life, as would be expected in neonatal jaundice). Women in both treatment groups maintained virologic suppression to <50 copies/mL (1 patient had a single blip to 59 copies/mL), and none of the infants was HIV infected.
| Clinical Bottom Line|
In this small study, ATV/r at 300/100 mg daily in the third trimester of pregnancy (given with zidovudine + lamivudine) appeared to maintain adequate Cmin in most women, and it was effective in both suppressing maternal HIV viremia and preventing HIV transmission to infants. These data will help in determining the appropriate dosage of ATV/r for pregnant women. It should be noted that, in this study as in others, there appeared to be significant individual variation in PK parameters, and some women may require higher dosages than others.
ATV/r is designated by the U.S. Public Health Service Task Force perinatal guidelines as an alternative agent for use in HIV-infected pregnant women. Atazanavir is in FDA Pregnancy Category B.
- Conradie F, Zorilla C, Josipovic D, et al; AI424182 Study Group. The safety, efficacy, and steady state pharmacokinetics of atazanavir/ritonavir (ATV/r) once daily given in combination with twice daily AZT/3TC during pregnancy: results of study AI424182. In: Program and abstracts of the 5th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; July 19-22, 2009; Cape Town, South Africa. Abstract LBPEB06.