Factors affecting antiretroviral pharmacokinetics in HIV-infected women with virologic suppression on combination antiretroviral therapy: a cross-sectional study
1 Women’s College Research Institute, Women’s College Hospital, 790 Bay Street, Room 736, Toronto, Ontario M5G 2N8, Canada
2 Department of Medicine, University of Toronto, Toronto, Ontario, Canada
3 University Health Network, Toronto, Ontario, Canada
4 McGill University Health Centre, Montreal Chest Institute, Montreal, Quebec, Canada
5 Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
6 Department of Medicine, University of Toronto, Toronto, Ontario, Canada
7 Oak Tree Clinic, BC Women’s Hospital and Health Centre, Vancouver, British Columbia, Canada
8 Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
9 Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
10 Ottawa Hospital Research Institute, Toronto, Ontario, Canada
11 Department of Medicine, University of Ottawa, Toronto, Ontario, Canada
12 Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
13 Department of Medicine, St. Michael’s Hospital, Toronto, Ontario, Canada
14 Windsor Regional Hospital Metropolitan Campus, Windsor, Ontario, Canada
15 Department of Medicine, Division of Infectious Diseases, Dalhousie University, Halifax, Nova Scotia, Canada
16 Victoria General Hospital, Halifax, Nova Scotia, Canada
17 Faculty of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, British Columbia, Canada
18 Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
19 Centre Hospitalier De L’Universite De Montreal, Hopital Notre-Dame, Montreal, Québec, Canada
20 University of Ottawa Health Services, Ottawa, Ontario, Canada
21 Centre Hospitalier Universitaire de Quebec – pavillon CHUL, Quebec, Quebec, Canada
BMC Infectious Diseases 2013, 13:256 doi:10.1186/1471-2334-13-256Published: 3 June 2013
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.
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.
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.
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.