Premium
Changes in viral loads of lamivudine‐resistant mutants and evolution of HBV sequences during adefovir dipivoxil therapy
Author(s) -
Suzuki Fumitaka,
Kumada Hiromitsu,
Nakamura Hirotoshi
Publication year - 2006
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.20658
Subject(s) - adefovir , lamivudine , virology , hepatitis b virus , reverse transcriptase , hbeag , virus , viral load , biology , medicine , polymerase chain reaction , hbsag , genetics , gene
The addition of adefovir dipivoxil (ADV) to ongoing lamivudine therapy is effective against lamivudine‐resistant virus in patients with hepatitis B virus (HBV) infection. We studied 39 patients who received ADV added to lamivudine for breakthrough hepatitis. We determined early viral changes (12 weeks) in YMDD mutants (rtM204I [YIDD sequence], rtM204V [YVDD]) and rtL180M in all 39 patients as well as amino acid changes in the polymerase reverse transcriptase (rt) region and precore/core promoter mutations in 15 patients who received long‐term treatment (more than 1 year). Changes in rtM204I and rtL180M viral loads were greater than that of the rtM204V, albeit statistically insignificant. Moreover, the greatest change in viral load was seen for rtM204I without hepatitis B e antigen (HBeAg). The precore mutant was replaced with wild‐type virus in three of eight patients after 1 year of added ADV therapy. Compared to baseline with lamivudine therapy only, new amino acid mutations were seen in the rt region at baseline with ADV in seven patients. At 1 year after ADV coadministration, the YMDD motif was replaced with wild‐type (rt204M) in two patients, in whom mutations were fewer and of a different type. We conclude that the rtM204I may be more sensitive to ADV in vivo. ADV tended to select wild‐type virus from precore mutants. Moreover, viruses that were wild‐type in the rt region reappeared after 1 year of ADV coadministration in some patients. J. Med. Virol. 78:1025–1034, 2006. © 2006 Wiley‐Liss, Inc.