title: Reduced indinavir exposure during pregnancy.
abstract: OBJECTIVE
  To describe the pharmacokinetics and safety of indinavir boosted with ritonavir (IDV/r) during the second and third trimesters of pregnancy and in the post-partum period.
  
  
  METHODS
  IMPAACT P1026s is an on-going, prospective, non-blinded study of antiretroviral pharmacokinetics (PK) in HIV-infected pregnant women with a Thai cohort receiving IDV/r 400/100 mg twice daily during pregnancy through to 6-12 weeks post-partum as part of clinical care. Steady-state PK profiles were performed during the second (optional) and third trimesters and at 6-12 weeks post-partum. PK targets were the estimated 10(th) percentile IDV AUC (12.9 μg ml(-1)h) in non-pregnant historical Thai adults and a trough concentration of 0.1 μg ml(-1), the suggested minimum target.
  
  
  RESULTS
  Twenty-six pregnant women were enrolled; thirteen entered during the second trimester. Median (range) age was 29.8 (18.9-40.8) years and weight 60.5 (50.0-85.0) kg at the third trimester PK visit. The 90% confidence limits for the geometric mean ratio of the indinavir AUC(0,12 h) and Cmax during the second trimester and post-partum (ante : post ratios) were 0.58 (0.49, 0.68) and 0.73 (0.59, 0.91), respectively; third trimester/post-partum AUC(0,12 h) and Cmax ratios were 0.60 (0.53, 0.68) and 0.63 (0.55, 0.72), respectively. IDV/r was well tolerated and 21/26 women had a HIV-1 viral load < 40 copies ml(-1) at delivery. All 26 infants were confirmed HIV negative.
  
  
  CONCLUSIONS
  Indinavir exposure during the second and third trimesters was significantly reduced compared with post-partum and ∼30% of women failed to achieve a target trough concentration. Increasing the dose of IDV/r during pregnancy to 600/100 mg twice daily may be preferable to ensure adequate drug concentrations.
authors.affiliation: Program for HIV Prevention and Treatment (IRD URI 174), Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Harvard School of Public Health, Boston, MA, USA; Institut de Recherché pour le Développement (IRD), UMI 174-PHPT, Marseille, France.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.forename: Brookie M
authors.initials: BM
authors.lastname: Best
authors.forename: Jullapong
authors.initials: J
authors.lastname: Achalapong
authors.forename: Alice
authors.initials: A
authors.lastname: Stek
authors.forename: Jiajia
authors.initials: J
authors.lastname: Wang
authors.forename: Nantasak
authors.initials: N
authors.lastname: Chotivanich
authors.forename: Prapap
authors.initials: P
authors.lastname: Yuthavisuthi
authors.forename: Pornnapa
authors.initials: P
authors.lastname: Suriyachai
authors.forename: Sinart
authors.initials: S
authors.lastname: Prommas
authors.forename: David E
authors.initials: DE
authors.lastname: Shapiro
authors.forename: D Heather
authors.initials: DH
authors.lastname: Watts
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Smith
authors.forename: Edmund
authors.initials: E
authors.lastname: Capparelli
authors.forename: Regis
authors.initials: R
authors.lastname: Kreitchmann
authors.forename: Mark
authors.initials: M
authors.lastname: Mirochnick
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000635:transmission; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D049590:Postpartum Period; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir; D019438:Ritonavir
keywords: HIV; antiretrovirals; pregnancy; prevention of mother-to-child transmission