Clinical course of chronic hepatitis B patients receiving nucleos(t)ide analogues after virological breakthrough during monotherapy with lamivudine.
Little is known about the optimal management of patients with chronic hepatitis B (CHB) who develop drug resistance. The aim of this study was to investigate the effectiveness of different drug regimens in chronically HBV-infected patients. HBV viral load was determined using a bDNA assay and the substitutions in HBV-DNA were studied by polymerase sequencing test. The study involved 38 patients who experienced a therapeutic failure to lamivudine (LAM). The sequential treatments used were: LAM + adefovir (ADV), LAM + tenofovir (TDF), entecavir (ETV) monotherapy, ADV monotherapy and TDF monotherapy. Similar activity against HBV replication was observed with all drug regimens. Of the patients treated with LAM, 44% developed resistance mutations. The rt M204I mutation was observed more frequently. Sequential ADV add-on LAM and TDF therapy induced the appearance of resistance in 3/18 (16.6%) and in 1/8 (5.5%) treated patients, respectively. Genotype D was the most prevalent (78.9%), followed by genotype A (13%), genotype E (5.2%) and genotype C (2.6%). Our study showed that baseline serum HBV DNA is an important predictor of virologic response and that virologic breakthrough is significantly associated with the insurgence of genotypic resistance.
Institute of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, Italy.
Maria Antonia
MA
De Francesco
Franco
F
Gargiulo
Angiola
A
Spinetti
Serena
S
Zaltron
Cinzia
C
Giagulli
Francesca
F
Caccuri
Francesco
F
Castelli
Arnaldo
A
Caruso
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; 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; D012189:Retrospective Studies; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D014763:Viral Matrix Proteins; D055815:Young Adult
D000998:Antiviral Agents; D063065:Organophosphonates; D014763:Viral Matrix Proteins; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine