title: Factors affecting antiretroviral pharmacokinetics in HIV-infected women with virologic suppression on combination antiretroviral therapy: a cross-sectional study.
abstract: BACKGROUND
  Although some studies show higher antiretroviral concentrations in women compared to men, data are limited. We conducted a cross-sectional study of HIV-positive women to determine if protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) C(min) and Cmax values were significantly different than historical general population (predominantly male) averages and to evaluate correlates of higher concentrations.
  
  
  METHODS
  HIV-positive women with virologic suppression (viral load < 50copies/mL) on their first antiretroviral regimen were enrolled. Timed blood samples for C(min) and Cmax were drawn weekly for 3 weeks. The ratio of each individual's median C(min) and Cmax to the published population mean values for their PI or NNRTI was calculated and assessed using Wilcoxon sign-rank. Intra- and inter-patient variability of antiretroviral drug levels was assessed using coefficient of variation and intra-class correlation. Linear regression was used to identify correlates of the square root-transformed C(min) and Cmax ratios.
  
  
  RESULTS
  Data from 82 women were analyzed. Their median age was 41 years (IQR=36-48) and duration of antiretrovirals was 20 months (IQR=9-45). Median antiretroviral C(min) and Cmax ratios were 1.21 (IQR=0.72-1.89, p=0.003) (highest ratios for nevirapine and lopinavir) and 0.82 (IQR=0.59-1.14, p=0.004), respectively. Nevirapine and efavirenz showed the least and unboosted atazanavir showed the most intra- and inter-patient variability. Higher CD4+ count correlated with higher C(min). No significant correlates for Cmax were found.
  
  
  CONCLUSIONS
  Compared to historical control data, C(min) in the women enrolled was significantly higher whereas Cmax was significantly lower. Antiretroviral C(min) ratios were highly variable within and between participants. There were no clinically relevant correlates of drug concentrations.
  
  
  BACKGROUND
  NCT00433979.
authors.affiliation: Women's College Research Institute, Women's College Hospital, 790 Bay Street, Room 736, Toronto, Ontario M5G 2N8, Canada. mona.loutfy@wchospital.ca
authors.forename: Mona Rafik
authors.initials: MR
authors.lastname: Loutfy
authors.forename: Sharon Lynn
authors.initials: SL
authors.lastname: Walmsley
authors.forename: Marina Barbara
authors.initials: MB
authors.lastname: Klein
authors.forename: Janet
authors.initials: J
authors.lastname: Raboud
authors.forename: Alice Lin-In
authors.initials: AL
authors.lastname: Tseng
authors.forename: Sandra Lauren
authors.initials: SL
authors.lastname: Blitz
authors.forename: Neora
authors.initials: N
authors.lastname: Pick
authors.forename: Brian
authors.initials: B
authors.lastname: Conway
authors.forename: Jonathan Benjamin
authors.initials: JB
authors.lastname: Angel
authors.forename: Anita Rochelle
authors.initials: AR
authors.lastname: Rachlis
authors.forename: Kevin
authors.initials: K
authors.lastname: Gough
authors.forename: Jeff
authors.initials: J
authors.lastname: Cohen
authors.forename: David
authors.initials: D
authors.lastname: Haase
authors.forename: David
authors.initials: D
authors.lastname: Burdge
authors.forename: Fiona Mary
authors.initials: FM
authors.lastname: Smaill
authors.forename: Alexandra
authors.initials: A
authors.lastname: de Pokomandy
authors.forename: Hugues
authors.initials: H
authors.lastname: Loemba
authors.forename: Sylvie
authors.initials: S
authors.lastname: Trottier
authors.forename: Charles Jean
authors.initials: CJ
authors.lastname: la Porte
mesh_terms: D000328:Adult; D000480:Alkynes; D044966:Anti-Retroviral Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D019829:Nevirapine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D009842:Oligopeptides / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D012307:Risk Factors; D019562:Viral Load
chemical_list: D000480:Alkynes; D044966:Anti-Retroviral Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019829:Nevirapine; C098320:efavirenz