Lamivudine-resistance mutations can be selected even at very low levels of hepatitis B viraemia.
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.


CONCLUSIONS
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.
Svicher
Valentina
V
University of Rome Tor Vergata, Italy.
Alteri
Claudia
C
Gori
Caterina
C
Salpini
Romina
R
Marcuccilli
Fabbio
F
Bertoli
Ada
A
Longo
Roberta
R
Bernassola
Martina
M
Gallinaro
Valentina
V
Romano
Sara
S
Visca
Michela
M
Ursitti
Antonella
A
Feasi
Marcello
M
Micheli
Valeria
V
Angelico
Mario
M
Cassola
Giovanni
G
Parruti
Giustino
G
Gubertini
Guido
G
De Sanctis
Giuseppe Maria
GM
Ceccherini-Silberstein
Francesca
F
Cappiello
Giuseppina
G
Spanò
Alberto
A
Perno
Carlo Federico
CF
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology*; D004279:DNA, Viral; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000494:pharmacology; D019562:Viral Load; D014766:Viremia
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil