Factors affecting antiretroviral pharmacokinetics in HIV-infected women with virologic suppression on combination antiretroviral therapy: a cross-sectional study

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• 作者：Mona Rafik Loutfy (22) (23)
  Sharon Lynn Walmsley (23) (24)
  Marina Barbara Klein (22)
  Janet Raboud (23) (24)
  Alice Lin-in Tseng (24) (24)
  Sandra Lauren Blitz (24)
  Neora Pick (22) (23)
  Brian Conway (24)
  Jonathan Benjamin Angel (22) (23)
  Anita Rochelle Rachlis (23) (24)
  Kevin Gough (22) (23)
  Jeff Cohen (23)
  David Haase (22) (24)
  David Burdge (22) (23)
  Fiona Mary Smaill (24)
  Alexandra de Pokomandy (22) (22)
  Hugues Loemba (22) (23)
  Sylvie Trottier (24)
  Charles Jean la Porte (22) (23)
  
• 关键词：HIV ; Women ; Antiretroviral therapy ; Pharmacokinetics
• 刊名：BMC Infectious Diseases
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：13
• 期：1
• 全文大小：262KB
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  49. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/256/prepub
  
• 作者单位：Mona Rafik Loutfy (22) (23)
  Sharon Lynn Walmsley (23) (24)
  Marina Barbara Klein (22)
  Janet Raboud (23) (24)
  Alice Lin-in Tseng (24) (24)
  Sandra Lauren Blitz (24)
  Neora Pick (22) (23)
  Brian Conway (24)
  Jonathan Benjamin Angel (22) (23)
  Anita Rochelle Rachlis (23) (24)
  Kevin Gough (22) (23)
  Jeff Cohen (23)
  David Haase (22) (24)
  David Burdge (22) (23)
  Fiona Mary Smaill (24)
  Alexandra de Pokomandy (22) (22)
  Hugues Loemba (22) (23)
  Sylvie Trottier (24)
  Charles Jean la Porte (22) (23)
  
  22. Centre Hospitalier De L’Universite De Montreal, Hopital Notre-Dame, Montreal, Québec, Canada
  23. University of Ottawa Health Services, Ottawa, Ontario, Canada
  24. Centre Hospitalier Universitaire de Quebec -pavillon CHUL, Quebec, Quebec, Canada
  

文摘

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) Cmin 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 Cmin and Cmax were drawn weekly for 3 weeks. The ratio of each individual’s median Cmin 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 Cmin 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 Cmin 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 Cmin. No significant correlates for Cmax were found. Conclusions Compared to historical control data, Cmin in the women enrolled was significantly higher whereas Cmax was significantly lower. Antiretroviral Cmin ratios were highly variable within and between participants. There were no clinically relevant correlates of drug concentrations. Trial registration NCT00433979