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Long-term hepatitis B virus dynamics in HIVhepatitis B virus-co-infected patients treated with tenofovir disoproxil fumarate

Lacombe, Karinea,b; Gozlan, Joëlc; Boelle, Pierre-Yvesa,d; Serfaty, Lawrencee; Zoulim, Fabienf; Valleron, Alain-Jacquesa,d; Girard, Pierre-Marieb

Basic Science

Background: The long-term impact of tenofovir disoproxil fumarate (TDF) on hepatitis B virus (HBV) replication has not yet been studied in HIV–HBV-co-infected patients.

Methods: We conducted a prospective study of HBV-DNA decay kinetics in 28 HIV–HBV-co-infected patients treated by TDF. HBV dynamics were studied using mixed linear models, and baseline factors affecting them were analysed using Cox models.

Results: The HBV-DNA load declined by a mean of 4.6 log copies/ml during follow-up (mean 71 weeks), and fell below the detection limit (200 copies/ml) in 21 patients. Inhibition of viral replication by TDF was associated with a decrease in alanine aminotransferase levels (125 versus 68 IU, P < 0.05). HBV-DNA decay was biphasic, with an rapid fall followed by a gradual decline. Baseline factors associated with a steeper first slope in the HBV-DNA decrease were high HBV load, positive hepatitis B e antigen (HBeAg) and YMDD mutations. Baseline factors increasing the time to reach an HBV-DNA level less than 200 copies/ml were high HBV load (150 days when HBV-DNA < 108 log, 316 days when HBV-DNA > 108 log) and positive HBeAg. Previous exposure to lamivudine or TDF–lamivudine did not modify HBV-DNA decrease under therapy in this population with a high prevalence of YMDD mutations.

Conclusion: The long-term decline in HBV DNA under TDF is biphasic and is primarily influenced by the initial HBV load. However, the clinical significance of such an association remains moderate, and TDF can be efficiently included in the highly active antiretroviral therapy regimen of HIV–HBV-co-infected patients, regardless of HBV strains and their degree of replication.

From the aInserm U707, Université Pierre et Marie Curie, 27 rue de Chaligny, 75571 Paris cedex 12, France

bService de Maladies Infectieuses et Tropicales

cService de Bactériologie-Virologie

dService de Santé Publique

eService d'Hépato-gastro-entérologie, Hôpital Saint-Antoine, AP-HP, 184 rue du Faubourg Saint-Antoine, 75012 Paris, France

fUnité Inserm 271, Institut Universitaire de France, 151 cours Albert Thomas, 69003 Lyon, France.

Received 20 October, 2004

Revised 5 January, 2005

Accepted 21 January, 2005

Correspondence to Karine Lacombe, Service de Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, AP-HP, 184 rue du Faubourg Saint-Antoine, 75012 Paris, France. Tel: +33 1 49 28 24 38; fax: +33 1 49 28 21 49; e-mail: karine.lacombe@sat.aphp.fr

© 2005 Lippincott Williams & Wilkins, Inc.