Safety and efficacy of adefovir dipivoxil in patients infected with lamivudine-resistant hepatitis B and HIV-1 * Yves Benhamou 1, * , Vincent Thibault 2 , Pamela Vig 4 , Vincent Calvez 2 , Anne-Genevieve Marcelin 2 , Marie-He ´le `ne Fievet 3 , Graeme Currie 4 , Chuy G. Chang 4 , Lu Biao 4 , Shelly Xiong 4 , Carol Brosgart 4 , Thierry Poynard 1 1 Groupe Hospitalier Pitie-Salpetriere, Service de d’He ´pato-Gastroente ´rologie, Paris, France 2 Groupe Hospitalier Pitie-Salpetriere, Laboratoire Institutions:de Virologie, Paris, France 3 Groupe Hospitalier Pitie-Salpetriere, Service de Pharmacie, Paris, France 4 Gilead Sciences, Foster City, Foster City, California, CA, USA See Editorial, pages 1–3 Background/Aims: Adefovir dipivoxil (10 mg once-daily) was added to antiretroviral therapy including lamivudine in 35 HIV/HBV co-infected patients. Methods: Parameters evaluated included alanine aminotransferase (ALT), HBV DNA and serological markers, HIV- 1 RNA, and CD4C cell count. Results: Twenty-nine patients (83%) completed 144 weeks. Serum HBV DNA declined from a baseline 9.76 log10 copies/mL (median) to 4.68, 5.24, and 5.90 log10 copies/mL at weeks 48, 96, and 144, respectively (P!0.0001 at all time points). Seven patients (25%) achieved HBV DNA!2.3 log10 copies/mL. No adefovir-associated resistance mutations in HBV DNA polymerase or HIV-1 reverse transcriptase were detected. ALT declined from 81 IU/L (median) at baseline by K16.0, K44.5, and K46.0 IU/L at week 48, 96 and 144, respectively (PZ!0.05, respectively), and normalized in 71% of patients (20 of 28) by week 144. Two patients developed antibodies against HB ‘e’ antigen by week 48. No serious adverse events related to adefovir dipivoxil occurred during the study, and HIV-1 RNA and CD4C cell counts were stable. Conclusions: Treatment with adefovir dipivoxil for 144 weeks was well tolerated and resulted in significant and sustained reductions in HBV DNA and ALT in HIV/HBV co-infected patients. Efficacy increased with treatment duration, with no loss of viral suppression. q 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Keywords: Adefovir dipivoxil; Chronic hepatitis B; Human immunodeficiency virus; Lamivudine-resistance; Clinical trial 1. Introduction Chronic infection with hepatitis B virus (HBV) affects approximately 400 million people worldwide [1]. Individuals with chronic HBV are at increased risk of liver cirrhosis and hepatocellular carcinoma (HCC) [2]. Among human immunodeficiency virus type 1 (HIV-1)-infected individuals, the prevalence of chronic HBV infection is approximately 5–10% and is associated with a higher risk of cirrhosis [2,3]. The natural history of chronic hepatitis B is modified by HIV-1 co-infection with higher risk of development and persistence of chronic HBV [4,5]. Recent studies show HBV/HIV-1 infected patients have a signifi- cantly increased risk of death from liver disease [3,6]. Lamivudine is effective in reducing serum HBV levels in HIVC and HIV-chronic HBV patients. However, Journal of Hepatology 44 (2006) 62–67 www.elsevier.com/locate/jhep 0168-8278/$30.00 q 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jhep.2005.08.020 Received 16 March 2005; received in revised form 21 July 2005; accepted 5 August 2005; available online 23 September 2005 * The authors who have taken part in this study have declared a relationship with the manufacturers of the drugs involved and they received funding from the drug companies involved to carry out their research. * Corresponding author. E-mail address: ybenhamou@teaser.fr (Y. Benhamou).