The use of a darunavir/ritonavir once-daily regimen in two pregnant women

Purpose of the study

Darunavir (DRV) is a second generation protease inhibitor (PI), first licensed for use in 2006. It is indicated for use in a treatment experienced population and is effective in vitro against both wild type and PI-resistant HIV. As a relatively new drug there is little published information on the pharmacokinetics of darunavir in pregnancy. Here we examine the pharmacokinetics of darunavir/ritonavir [DRV/r 800/100mg once daily (OD)] in two women, over the course of pregnancy and postpartum.

Methods

A prospective open labelled study was established to enrol HIV positive pregnant women on DRV/r as part of their routine maternity care. DRV plasma trough concentrations were determined in the first (T1) and/or second (T2) and/or third (T3) trimester using a validated HPLC-MS/MS methodology with a limit quantification of 16 ng/ml. Postpartum (PP) sampling was also performed.

Summary of results

To date two women have been recruited. Both were black African and initiated treatment prior to pregnancy. Each woman was virally suppressed (HIV RNA <50 cpm) throughout pregnancy and had CD4 cell counts >300 cells/mm³ (range 341-470). Patient 1 had a TDM sample drawn in each trimester and at PP. DRV concentrations in T1 [3790ng/ml], T2 [1285ng/ml] and T3 [1773ng/ml] were considerably (27-75%) lower relative to concentrations at PP [5227ng/ml]. Patient 2 had TDM samples taken in T2 and PP only. Again a considerably lower (~72%) DRV concentration was noted at T2 compared with PP. In both cases, DRV concentrations in pregnancy and postpartum were above the accepted minimum effective concentration for wt virus (MEC; 550 ng/ml, based on in vitro studies).

Conclusions

In the two cases examined, DRV/r (800/100mg, OD) was effective at achieving adequate therapeutic drug levels (>550ng/ml) during pregnancy. However, reduced DRV plasma concentrations in the second/third trimesters, highlights the need for TDM in this population, and warrants further study of pregnancy-associated changes in DRV pharmacokinetics.