Sustained virological and biochemical responses to lamivudine and adefovir dipivoxil combination in a chronic hepatitis B infection despite mutations conferring resistance to both drugs

Sylvie Larrat¹ , Marie-Noëlle Hilleret² , Raphaele Germi¹ , Julien Lupo¹ , Sandrine Nicod¹ , Jean-Pierre Zarski² , Jean-Marie Seigneurin¹ and Patrice Morand¹

¹Laboratoire de Virologie moléculaire et structurale, CHU de Grenoble BP 217, 38043 Grenoble cedex 09, France

²Département d'hépatogastroentérologie, CHU de Grenoble BP 217, 38043 Grenoble cedex 09, France

author email corresponding author email

Comparative Hepatology 2008, 7:3doi:10.1186/1476-5926-7-3


Published:	12 March 2008

Abstract

Background

Sequential monotherapies of nucleotide analogs used in chronic hepatitis B treatment can lead to the selection of a resistance mutation to each antiviral drug.

Case presentation

A patient with chronic hepatitis B was successively treated with lamivudine monotherapy, lamivudine-adefovir dual therapy, adefovir monotherapy and again with an adefovir-lamivudine dual therapy. Lamivudine-associated mutations (rtL180M and rtM204V/I) followed by adefovir-associated mutations (rtN236T and rtA181V) emerged during the two monotherapy regimens. Despite the presence of rtM204V/I, rtA181V, and rtN236T mutations at the beginning of the second dual therapy, sustained biochemical and virological responses have been observed thus far after 23 months.

Conclusion

This case illustrates that rtM204V/I, rtA181V, and rtN236T resistance mutations can coexist in a patient but do not preclude the recycling of lamivudine and adefovir in combination therapy, when no other therapeutic choices are available.