Darunavir Use During Pregnancy
In this phase 4 study women receiving DRV/r 600 mg/100 mg twice daily or 800 mg/100 mg once daily, or ATV/r 300 mg/100 mg once daily during pregnancy were enrolled. Plasma concentrations were obtained pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours in the third trimester and at least 2 weeks postpartum. Where possible a cord blood sample and matching maternal blood sample were taken at delivery. Plasma concentrations were determined using a validated UPLC method.
Women were a median of 33.5 years of age. Their background regimens were: TDF+3TC (n=12), AZT+3TC (n=4), ABC+3TC (n=3), AZT+3TC+TDF (n=3) and one woman received DRV/r monotherapy.
Data were available for 6 women receiving DRV/r 800/100 mg once daily (3 did not have postpartum concentrations) and 3 receiving 600/100 mg twice daily. For ATV/r 300/100 mg once daily, data were available for 13 women. Cord blood and maternal samples were available for 5 women receiving DRV/r and 7 ATV/r.
This study found exposure (AUCtau) during pregnancy to DRV, ATV and RTV was decreased by respectively 36%, 33% and 53% compared to post-partum. The investigators suggested that increased volume of distribution or decreased absorption could explain this. They added that as the half-life seems to be similar during and after pregnancy, increased elimination is less likely to be the reason.
They noted that concomitant use of tenofovir (used by 14 patients) did not appear to influence DRV or ATV exposure.
In this study 2/9 women receiving DRV had concentrations below the target concentration in the 3rd trimester.
The ratio of cord blood/maternal concentrations ranged from 0.11-0.67 (n=7) and was <0.76 for DRV (n=5).
All children were HIV-negative and no birth defects were reported.
Data from these studies suggest that twice daily dosing with darunavir 600mg/ritonavir 100 mg provides adequate drug exposure during pregnancy.
However, the data from the PANNA study on a small sample of women taking once daily darunavir 800mg/ritonavir 100mg and data from Capparelli et al presented at the Rome paediatric workshop last year show much lower trough concentrations, which in some cases are below that recommended to achieve viral suppression.4,5
Until more data are available twice-daily darunavir at the standard dose should be prescribed and TDM used to monitor the use of once daily darunavir during pregnancy.
This article was provided by HIV i-Base. It is a part of the publication HIV Treatment Bulletin. Visit HIV i-Base's website to find out more about their activities, publications and services.
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