Selection and counterselection of the rtI233V adefovir resistance mutation during antiviral therapy.
Recently, we reported on three patients with chronic hepatitis B virus (HBV) infection for whom adefovir (ADF) therapy virologically failed, most likely due to a preexisting rtI233V HBV polymerase mutation. Here, we describe two further patients with chronic HBV infection who were found to develop the rtI233V mutation after initiation of ADF therapy. These patients represent the first cases known so far in which the rtI233V ADF resistance mutation evolved under persistent HBV replication during HBV therapy with ADF. Interestingly, one of the previously described patients, who was initially successfully switched from ADF to tenofovir (TDF) and became virologically suppressed subsequently, experienced a moderate but remarkable rebound of HBV viremia after switching from TDF to entecavir, due to the emergence of renal toxicity. Thus, we provide evidence for the selection and counterselection of the rtI233V ADF resistance mutation during antiviral therapy.
Schildgen
Oliver
O
Institut für Pathologie, Kliniken der Stadt Köln, Cologne, Germany.
Olotu
Cynthia
C
Funk
Anneke
A
Zöllner
Bernhard
B
Helm
Martin
M
Rockstroh
Jürgen Kurt
JK
Sirma
Hüseyin
H
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D012641:Selection, Genetic; D016415:Sequence Alignment; D000068698:Tenofovir; D017211:Treatment Failure; D014766:Viremia; D055815:Young Adult
D000998:Antiviral Agents; D063065:Organophosphonates; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine