Reuters Health Information (2009-03-04): HBV polymerase resistance mutations may be antagonistic
HBV polymerase resistance mutations may be antagonistic
Last Updated: 2009-03-04 16:57:02 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Susceptibility of hepatitis B virus (HBV) previously resistant to lamivudine may be restored as resistance to adefovir develops, according to a report in the March Journal of Medical Virology.
"Most bacterial- and HIV-resistance is cumulative; newly acquired resistance comes on top of existing resistance," Dr. Hans L. Zaaijer from Academic Medical Center, University of Amsterdam, told Reuters Health. "Fortunately, it seems that HBV sometimes is forced to choose between resistance mechanisms."
Dr. Zaaijer and colleagues described the effect of lamivudine and adefovir combination in two patients who were resistant not only to lamivudine, but also to adefovir. They underwent serial monotherapy with lamivudine and then adefovir.
Complete virological breakthrough occurred in both patients during lamivudine monotherapy and then again during adefovir monotherapy, the authors report.
After lamivudine was ultimately added to adefovir, the adefovir resistance mutation persisted in both patients in all clones, but the lamivudine-related mutations did not return.
During combination therapy, the HBV-DNA level decreased 1000-fold despite the earlier virological breakthrough during lamivudine monotherapy, the researchers note.
"Apparently," the investigators say, "HBV resistance to different HBV polymerase inhibitors may be antagonistic; resistance to one drug may restore the susceptibility to another drug."
"Antagonistic HBV resistance mechanisms deserve further attention," the authors conclude. "If chronic hepatitis B is to be treated with a combination of drugs, a combination of drugs with antagonistic patterns of resistance seems superior to other combinations of HBV inhibitors."
"Prescribing lamivudine plus adefovir for patients who failed on serial monotherapy with these drugs is not advisable," Dr. Zaaijer explained. "Nowadays new potent HBV inhibitors, rarely inducing resistance, are available."
He added, "Regarding long-time suppression of HBV in naive patients, monotherapy with tenofovir or entecavir seems the way to go. Nevertheless, in the long-run it may become necessary again to know which antiviral combinations display antagonistic resistance."
J Med Virol 2009;81:413-416.