Tenofovir monotherapy is effective in hepatitis B patients with antiviral treatment failure to adefovir in the absence of adefovir-resistant mutations.
OBJECTIVE
We sought to identify mutations associated with treatment failure to adefovir (ADV) and to determine virologic response to tenofovir (TDF) alone and in combination with emtricitabine (FTC) in these patients.


METHODS
Serum samples prior to and after the change in treatment to TDF/TDF+FTC from 13 patients were analyzed by direct sequencing and clonal analysis.


RESULTS
ADV-resistant mutations, rtA181V and rtN236T, were detected on direct sequencing in 3 of 8 patients who had virologic breakthrough. Among patients with suboptimal virologic response, rtA181T, rtI233V, and rtN236T were present on clonal analysis in 3 patients. Ten patients received TDF, 8 achieved virologic response. One had ADV-resistance at baseline and persistence of ADV-resistant mutations during TDF treatment, addition of FTC resulted in a further decrease in HBV DNA. Another patient had no ADV-resistance at baseline, and selection of ADV-resistant mutations during TDF treatment. All 3 patients who received TDF+FTC had undetectable HBV DNA within 3-12 months including 2 who had ADV-resistance at baseline.


CONCLUSIONS
TDF monotherapy is effective for patients with virologic breakthrough or suboptimal response to ADV, but combination therapy with a nucleoside analogue should be considered in patients with ADV-resistance. No novel mutations were detected.
Tan
Jessica
J
Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI 48109-0362, USA.
Degertekin
Bulent
B
Wong
Stephen N
SN
Husain
Munira
M
Oberhelman
Kelly
K
Lok
Anna S F
AS
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D006509:Hepatitis B / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D063065:Organophosphonates / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D000068698:Tenofovir; D017211:Treatment Failure; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; C053001:adefovir; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine