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Antimicrobial Agents and Chemotherapy, June 2004, p. 2091-2096, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2091-2096.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Interactions between Atazanavir-Ritonavir and Tenofovir in Heavily Pretreated Human Immunodeficiency Virus-Infected Patients

Anne-Marie Taburet,1* Christophe Piketty,2 Corine Chazallon,3 Isabelle Vincent,1 Laurence Gérard,3 Vincent Calvez,4 Francois Clavel,5 Jean-Pierre Aboulker,3 Pierre-Marie Girard,6 and the ANRS Protocol 107 Puzzle 2 Investigators{dagger}

Clinical Pharmacy Department, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris,1 Department of Immunology, Hôpital Georges Pompidou, Assistance Publique-Hôpitaux de Paris,2 Department of Virology, Hôpital Pitié Salpétrière, Assistance Publique-Hôpitaux de Paris,4 Department of Infectious Diseases Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris,5 Department of Virology, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris,6 INSERM SC10, Villejuif, France3

Received 22 November 2003/ Returned for modification 24 December 2003/ Accepted 10 February 2004

The aim of the present study was to assess the pharmacokinetic behavior of atazanavir-ritonavir when it is coadministered with tenofovir disoproxil fumarate (DF) in human immunodeficiency virus (HIV)-infected patients. Eleven patients enrolled in Agence Nationale de Recherche sur le SIDA (National Agency for AIDS Research, Paris, France) trial 107 were included in this pharmacokinetic study. They received atazanavir at 300 mg and ritonavir at 100 mg once a day (QD) from day 1 to the end of study. For the first 2 weeks, their nucleoside analog reverse transcriptase inhibitor (NRTI) treatments remained unchanged. Tenofovir DF was administered QD from day 15 to the end of the study. Ongoing NRTIs were selected according to the reverse transcriptase genotype of the HIV isolates from each patient. The values of the pharmacokinetic parameters for atazanavir and ritonavir were measured before (day 14 [week 2]) and after (day 42 [week 6]) initiation of tenofovir DF and are reported for the 10 patients who completed the study. There was a significant decrease in the area under the concentration-time curve from 0 to 24 h (AUC0-24) for atazanavir with the addition of tenofovir DF (AUC0-24 ratio, 0.75; 90% confidence interval, 0.58 to 0.97; P = 0.05). There was a trend for a decrease in the minimum concentrations of atazanavir and ritonavir in plasma when they were combined with tenofovir, but none of the differences reached statistical significance. The median decreases in the HIV RNA loads at week 2 and week 6 were 0.1 and 0.2 log copies/ml, respectively. In summary, our data are consistent with the existence of a significant interaction between atazanavir and tenofovir DF.

* Corresponding author. Mailing address: Clinical Pharmacy, Hospital Bicêtre-Assistance Publique Hôpitaux de Paris, 78 rue du Général Leclerc, 94270 Kremlin Bicêtre, France. Phone: 33 1 45 21 29 57. Fax: 33 1 45 21 28 60. E-mail: anne-marie.taburet{at}bct.ap-hop-paris.fr.

{dagger} Contributing members of the ANRS Protocol 107 Puzzle 2 Investigators are listed in Acknowledgments.

Antimicrobial Agents and Chemotherapy, June 2004, p. 2091-2096, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2091-2096.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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