Pharmacokinetics and Safety of Darunavir/Ritonavir in HIV-Infected Pregnant Women

Abstract

The dosage of darunavir/ritonavir is 800/100 mg once daily for treatment-naive patients or treatment-experienced patients with no prior darunavir resistance associated mutations, and 600/100 mg twice daily for treatment-experienced patients with one or more darunavir resistance associated mutations. Results from the five available pharmacokinetic studies show reductions in total darunavir plasma concentrations of between 20-50% during the third trimester of pregnancy. The unbound darunavir concentrations have been measured only in subsets of patients in two of the five pharmacokinetic studies. The unbound concentrations were 11% higher during pregnancy in one study of the 600/100 mg twice-daily dosage, and 13-38% lower during pregnancy for the 800/100 mg once-daily dosage. Ratios of darunavir concentration in cord blood compared to maternal plasma are in the range of 0.11-0.18, suggesting that darunavir does not have high trans-placental penetration. Despite the decrease in exposure, the darunavir/ritonavir 800/100 mg once-daily regimen in HIV-positive pregnant women in combination with background antiretroviral therapy has been effective in preventing mother-to-child transmission in the studies included in this review. Among the 137 infants born across the five studies, there was one case of mother-to-child transmission, which was in a mother taking the 600/100 mg twice-daily dose but who had documented poor adherence to treatment.