[The rate of hepatitis B virus resistance to adefovir dipivoxil (ADV) and the evolution of hepatitis B virus in lamivudine-resistant chronic hepatitis B patients with ADV monotherapy].
OBJECTIVE
To study the resistant rate of hepatitis B virus (HBV) to ADV and the dynamic evolution of HBV in lamivudine (Lam)-resistant chronic hepatitis B (CHB) patients.


METHODS
Twenty-three Lam-resistant CHB patients were assigned to a 10mg/d ADV monotherapy for 68-116 weeks. The baseline and different time point blood samples after ADV monotherapy were analyzed for ADV-resistant mutations using direct sequencing of PCR products; the evolution of HBV mutations was examined by clonal analysis of serial samples from one patient infected with ADV-associated resistant HBV strains.


RESULTS
The cumulative incidence of genotypic ADV resistance at weeks 48 and 96 was 4.3% and 10.5% respectively respectively. The evolution analysis of HBV mutant strains in an ADV-resistant CHB patient showed that the proportion of YMDD mutants gradually decreased with rtA181S mutants increasing over time after ADV monotherapy, and that rtA181S+N236T mutants became the predominant strains during prolonged ADV monotherapy. The addition of Lam to the ongoing ADV treatment had poorer antiviral response in the patient with rtA181S or rtA181S+N236T mutant infection; one clone with multi-drug resistant mutations was selected during Lam and ADV combination therapy.


CONCLUSIONS
Increased risk of adefovir resistance and selection of multi-drug resistant mutations are associated with long-term ADV monotherapy in patients with Lam-resistant chronic hepatitis B.
Qin
Yan-li
YL
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Zhang
Ji-ming
JM
Huang
Yu-xian
YX
Mao
Ri-cheng
RC
Yin
You-kuan
YK
Zhang
Wan-qin
WQ
Zhang
Qing-bo
QB
Wu
Xiang-hui
XH
Weng
Xin-hua
XH
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D019143:Evolution, Molecular; D005260:Female; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*
D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil