Relationship between Levels of Indinavir in Hair and Virologic Response to Highly Active Antiretroviral Therapy

15 October 2002 | Volume 137 Issue 8 | Pages 656-659

Background: Suboptimal levels of antiretroviral drugs result in virologic failure in HIV-infected patients treated with highly active antiretroviral therapy (HAART).

Objective: To assess the relationship between levels of indinavir in hair and virologic outcome.

Design: Cross-sectional study.

Setting: 7 AIDS clinics in France.

Patients: 89 HIV-infected patients who received HAART that included indinavir.

Measurements: Patients were classified as responders or nonresponders on the basis of viremia at the time of hair collection. In nonresponders, levels of indinavir in hair and resistance mutations in the protease gene were assessed at baseline and at the time of indinavir measurement.

Results: Mean indinavir levels (±SD) were significantly higher in the 65 responders than in the 24 nonresponders (24.4 ± 16 µg/g vs. 12.9 ± 8.6 µg/g) (P < 0.001). Nonresponders with intermediate levels of indinavir in hair had more mutations in the protease gene than did nonresponders with low levels of indinavir in hair.

Conclusion: Indinavir levels in hair are associated with virologic outcome in patients receiving HAART.

Editors' Notes Context Current methods for monitoring adherence to and the pharmacokinetics of highly active antiretroviral therapy (HAART) are inefficient and inaccurate. Patient reports tend to overestimate adherence, and blood levels reflect only the medication doses given most recently. A preliminary study suggested that indinavir levels in hair samples were higher in HIV-infected patients who responded to HAART than they were in nonresponders. Contribution This study confirms that indinavir levels in hair are higher in responders to HAART than in nonresponders. Intermediate levels of indinavir in hair were associated with drug-resistant variants of the virus. Implications Measurement of hair levels of antiretroviral drugs deserves further evaluation to establish its role in monitoring HIV-infected patients receiving HAART. –The Editors

 

Author and Article Information

From Geneva University Hospital and Laboratoire de Virologie, Geneva, Switzerland; Hôpital Paul-Brousse, Villejuif, France; Hôpital de la Croix Rousse, Lyons, France; Hôpital Bichat, Hôpital Rothschild, Hôpital Pitié-Salpêtrière, and Hôpital de la Croix Saint-Simon, Paris, France; Hôpital Raymond-Poincaré, Garches, France; and Hôpital du Bocage, Dijon, France.

Acknowledgments: The authors thank Huguette Berthé for technical assistance and Sylvie Cotigny for HIV genotyping. They also thank Dr. Firouzé Bani-Sadr, Professor Dominique Peyramond, Professor Henri Portier, and Professor Willy Rozenbaum for the referral of patients, and Professor Bernard Hirschel, Professor Luc Perrin, and Dr. Laurent Kaiser for critical review of the manuscript.

Grant Support: By GIPIT (Groupe d'Investigation en Pathologie Infectieuse et Tropicale) and in part by an unrestricted grant from Merck Sharp & Dohme, Paris, France.

Requests for Single Reprints: Louis Bernard, MD, Division of Infectious Diseases, Geneva University Hospital, rue Micheli-du-Crest, CH 1211 Geneva, Switzerland; e-mail, louis.bernard{at}hcuge.ch.

Current Author Addresses: Dr. Bernard: Division of Infectious Diseases, Rue Micheli-du-Crest, CH 1211 Geneva, Switzerland.

Dr. Vuagnat: INSERM U472 Epidémiologie et Biostatistiques, Hôpital Paul-Brousse, 91400 Villejuif, France.

Dr. Peytavin: Service de Toxicologie et Pharmacologie, Hôpital Bichat, 75019 Paris, France.

Dr. Hallouin: Laboratoire de Virologie, Rue Micheli-du-Crest, Genève, Switzerland.

Dr. Bouhour: Service des Maladies Infectieuses, Hôpital de la Croix Rousse, 69000, Lyons, France.

Dr. Nguyen: Service des Maladies Infectieuses, Hôpital Rothschild, 75012 Paris, France.

Dr. Vildé: Service des Maladies Infectieuses, Hôpital Bichat, 75019 Paris, France.

Dr. Bricaire: Service des Maladies Infectieuses, Hôpital Pitié-Salpêtrière, 75013 Paris, France.

Dr. Raguin: Service des Maladies Infectieuses, Hôpital de la Croix Saint-Simon, 75020 Paris, France.

Drs. de Truchis, Ghez, and Perronne: Service des Maladies Infectieuses et Tropicales, Hôpital Raymond-Poincaré, Faculté de Médecine Paris-Ouest, 92380 Garches, France.

Dr. Duong: Service des Maladies Infectieuses, Hôpital du Bocage, Dijon, France.

Author Contributions: Conception and design: L. Bernard, M.-C. Hallouin.

Analysis and interpretation of the data: L. Bernard, A. Vuagnat, G. Peytavin, M.-C. Hallouin, D. Ghez.

Drafting of the article: L. Bernard, A. Vuagnat, D. Ghez, C. Perronne.

Critical revision of the article for important intellectual content: L. Bernard, M.-C. Hallouin, D. Ghez, C. Perronne.

Final approval of the article: L. Bernard, P. de Truchis, C. Perronne.

Provision of study materials or patients: L. Bernard, D. Bouhour, T.H. Nguyen, J.L. Vildé, F. Bricaire, G. Raguin, M. Duong.

Statistical expertise: A. Vuagnat.

Obtaining of funding: P. de Truchis, C. Perronne.

Administrative, technical, or logistic support: I. Peytavin, M.-C. Hallouin, D. Bouhour, T.H. Nguyen, J.L. Vildé, F. Bricaire, G. Raguin, P. de Truchis, M. Duong.

Collection and assembly of data: L. Bernard, G. Peytavin, M.-C. Hallouin.