Sustained virological and biochemical responses to lamivudine and adefovir dipivoxil combination in a chronic hepatitis B infection despite mutations conferring resistance to both drugs.
Larrat S, Hilleret MN, Germi R, Lupo J, Nicod S, Zarski JP, Seigneurin JM, Morand P.
Laboratoire de Virologie moléculaire et structurale, CHU de Grenoble BP 217, 38043 Grenoble cedex 09, France. slarrat@chu-grenoble.fr.
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.
PMID: 18336716 [PubMed - in process]PMCID: PMC2322943