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Open Access Research article

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

Mona Rafik Loutfy12*, Sharon Lynn Walmsley23, Marina Barbara Klein4, Janet Raboud35, Alice Lin-in Tseng36, Sandra Lauren Blitz3, Neora Pick78, Brian Conway9, Jonathan Benjamin Angel1011, Anita Rochelle Rachlis122, Kevin Gough132, Jeff Cohen14, David Haase1516, David Burdge177, Fiona Mary Smaill18, Alexandra de Pokomandy194, Hugues Loemba1020, Sylvie Trottier21 and Charles Jean la Porte1011

Author Affiliations

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

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BMC Infectious Diseases 2013, 13:256  doi:10.1186/1471-2334-13-256

Published: 3 June 2013

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) 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

Keywords:
HIV; Women; Antiretroviral therapy; Pharmacokinetics