Monitoring of therapy in patients with chronic hepatitis B virus.
OBJECTIVE
The aims of this study were to evaluate therapy with lamivudine (LAM) and adefovir dipivoxil (ADV) monotherapy in chronic hepatitis B virus (HBV)-infected patients with frequent measurements of DNA levels, to characterize HBV genotypes, and to determine the emergence of nucleos(t)ide analogue mutants before and during the therapy by direct-sequencing the reverse transcriptase region and by INNO-LiPA HBV DR v3.


METHODS
A total of 15 chronic HBV patients were analysed: 11 were treated with ADV and four were treated with LAM.


RESULTS
Viral genotype was determined, showing the presence of genotype D (73%) in 11 patients and genotype A (27%) in four patients. In the viral response to treatment, three patients developed substitutions at rtM204I associated with LAM resistance and one of these patients presented rtM204V/I plus rtL180M mutation. In contrast, of the 11 patients treated with ADV, three patients developed mutations (rtN236T; rtA181V; rtA181V plus rtN236T). With regard to this case, the same results were observed by INNO-LiPA HBV DR v3 and direct sequencing, but by direct sequencing we detected an extra mutation rtQ215S that was present in two patients: one patient who was on treatment with LAM had an rtQ215S mutation in addition to an rtM204I, and the second patient treated with ADV had rtA181V.


CONCLUSIONS
Direct sequence analysis is an essential tool to optimize therapeutic management of HBV chronic infection in clinical practice to choose the appropriate nucleos(t)ide analogues and to detect extra mutations that are not included in the commercial kit.
Arrese
Elisabete
E
Department of Immunology, Pharmacy Faculty, University of the Basque Country, Vitoria-Gasteiz, Spain. eli.arrese@ehu.es
Basaras
Miren
M
Blanco
Sonia
S
Ruiz
Pablo
P
Cisterna
Ramon
R
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D016903:Drug Monitoring; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D017354:Point Mutation; D017422:Sequence Analysis, DNA
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil