Pharmacokinetics and Safety of Darunavir/Ritonavir in HIV-Infected Pregnant Women.
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.
Institute of Translational Medicine, University of Liverpool, and Royal Liverpool University Hospital, Liverpool, UK.
Saye
S
Khoo
Pharmaco-Toxicology Department, APHP, Bichat-Claude Bernard Hospital, Paris, France.
Gilles
G
Peytavin
Radboud University Medical Centre, Nijmegen, The Netherlands.
David
D
Burger
Institute of Translational Medicine, University of Liverpool, and Royal Liverpool University Hospital, Liverpool, UK.
Andrew
A
Hill
Janssen Scientific Affairs, Titusville, New Jersey, USA.
Kimberley
K
Brown
Janssen EMEA, Neuss, Germany.
Christiane
C
Moecklinghoff
Janssen, Tilburg, The Netherlands.
Charles
C
La Porte
Janssen EMEA, Issy-les-Moulineaux, France.
Maria Blanca
MB
Hadacek
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D000069454:Darunavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D019438:Ritonavir; D000069454:Darunavir