Clonal analysis of the quasispecies of antiviral― resistant HBV genomes in patients with entecavir resistance during rescue treatment and successful treatment of entecavir resistance with tenofovir

• Published in: Antiviral therapy 2013-01, Vol.18 (1), p.77-85
• Main Authors: KARATAYLI, Ersin, IDILMAN, Ramazan, KARATAYLI, Senem C, CEVIK, Emrah, YAKUT, Mustafa, SEVEN, Gülseren, KABACAM, Gökhan, MITHAT BOZDAYI, A, YURDAYDIN, Cihan
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; Adenine - therapeutic use; Adult; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Biological and medical sciences; Data processing; DNA; Drug Resistance, Viral - drug effects; Drug Resistance, Viral - genetics; Drug Therapy, Combination; Female; Genome, Viral - drug effects; Genome, Viral - genetics; Genomes; Guanine - analogs & derivatives; Guanine - pharmacology; Guanine - therapeutic use; Hepatitis B virus; Hepatitis B virus - classification; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - virology; Humans; Lamivudine; Lamivudine - therapeutic use; Male; Medical sciences; Middle Aged; Mutation; Organophosphonates - pharmacology; Organophosphonates - therapeutic use; Pharmacology. Drug treatments; Tenofovir; Treatment Outcome; Young Adult
• ISSN: 1359-6535; 2040-2058
• DOI: 10.3851/IMP2294

Clonal analysis of quasispecies of resistant HBV genomes in patients with entecavir (ETV) resistance receiving lamivudine (3TC) plus adefovir (ADV) rescue therapy has never been performed. A sample of 10 patients with ETV resistance who were switched to 3TC+ADV treatment were analysed for changes in viral quasispecies. Serum samples at baseline, and at months 3 and 6 of 3TC+ADV treatment could be clonally analysed in 7 of 10 patients; 3-82 clones per sample (total 1,068 clones, mean 63) were sequenced. 3TC+ADV therapy led to a modest decline in HBV DNA. Almost all clones had L180M and M204V 3TC resistance mutations before and during combination therapy. All clones had ≥1 of the S202G, T184F, T184A, T184L, T184I and M250V ETV resistance mutations. The percentages of detected clones bearing 3TC (rtL180M and rtM204V) and ETV mutations did not change with rescue 3TC+ADV therapy. In 7 of 8 patients with detectable HBV DNA (median 5.17 log(10) copies/ml) after a median 24 months of ADV therapy, HBV DNA became undetectable with 3TC plus tenofovir after 6 months of treatment. In patients with ETV resistance tenofovir is effective. Clonal analysis data indicate no selection of specific HBV mutants during rescue 3TC+ADV.