Lamivudine-resistance mutations can be selected even at very low levels of
hepatitis B viraemia
Valentina Svichera1, Claudia Alteria1, Caterina Gorib, Romina Salpinia, Fabbio
Marcuccillia, Ada Bertolia, Roberta Longoc, Martina Bernassolac, Valentina
Gallinarod, Sara Romanoc, Michela Viscac, Antonella Ursittic, Marcello Feasie,
Valeria Michelif, Mario Angelicoa, Giovanni Cassolae, Giustino Parrutig, Guido
Gubertinif, Giuseppe Maria De Sanctisd, Francesca Ceccherini-Silbersteina,
Giuseppina Cappielloc, Alberto Spanòc, Carlo Federico Pernoa
Received 21 January 2010; accepted 27 April 2010. published online 21 June
2010.
Corrected Proof
Abstract
Objective
To investigate lamivudine (LAM)-resistance profiles of hepatitis B virus (HBV)
at the early stages of virological breakthrough (serum HBV-DNA 12–345IU/ml)
or when HBV-DNA is undetectable.
Methods
Sixty-four HBV-mono-infected patients were enrolled: 25 had virological
breakthrough with serum HBV-DNA ranging from 12 to 345IU/ml during first-line
LAM-monotherapy; 24 were on LAM-monotherapy, and 15 were on LAM+adefovir
dipivoxil (ADV) with undetectable serum HBV-DNA (<12IU/ml).
Results
HBV-reverse transcriptase was successfully sequenced in 22 (88.0%) LAM-treated
patients with HBV-DNA between 12 and 345IU/ml, and in 12 (30.8%) patients
receiving LAM (±ADV) with HBV-DNA<12IU/ml.
Drug-resistance mutations were observed in 17 (77.2%) LAM-treated patients
with virological breakthrough: 8 M204V, 7 M204I, 1 M204I/V, and 1 A181T. One
or ≥2 compensatory mutations were found in 10 (58.8%) and in 4 (23.5%)
patients.
Drug-resistance mutations were present also in patients with undetectable
serum HBV-DNA: M204I was detected in 2 patients receiving LAM-monotherapy, and
V84M in 1 patient receiving LAM+ADV.
Conclusion
Overall findings support the existence of drug-resistance mutations even at
very low levels of viral replication. The persistence of low-level HBV
replication and consequent drug-resistance emergence should be considered when
choosing therapeutic strategies.
a University of Rome “Tor Vergata”, Italy
b I.N.M.I. “L. Spallanzani”, Rome, Italy
c “S. Pertini” Hospital, Rome, Italy
d University of Rome “La Sapienza”, Italy
e “Galliera” Hospital, Genoa, Italy
f “L. Sacco” Hospital, Milan, Italy
g “Spirito Santo” Hospital, Pescara, Italy
Corresponding author at: Department of Experimental Medicine, University of
Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy. Tel.: +39 06
72596566; fax: +39 06 72596039.