A dedicated specimen (i.e. no other tests to be performed) is required for this assay.
Do not use heparin tubes
Performed as requested. Result available within 10 working days.
This assay is designed to detect polymerase resistance by amplifying a 492 base pair fragment of the polymerase gene which is then sequenced and analysed for drug resistance associated mutations.
Lamivudine is an effective antiviral agent in the treatment of patients chronically infected with hepatitis B virus. It competitively inhibits viral reverse transcriptase and terminates proviral DNA chain extension, which leads to a marked decrease in HBV DNA levels, usually followed by improvements in alanine aminotransferase levels and liver histology. However, HBV strains with mutations in the conserved YMDD motif of the HBV polymerase gene emerge in an increasing proportion of patients after long-term mono-therapy with lamivudine.
Patients with resistance mutants characteristically develop HBV DNA breakthrough and rise in ALT. Addition of Adefovir dipivoxil (ADV) to the treatment regime is current practice.
In the majority of lamivudine-resistant isolates the mutations have been reported to occur within the YMDD motif of the viral polymerase, either as a single mutation M204I or as M204V concomitant with L180M.
Adefovir resistant virus has been reported and already detected in New Zealand. The mutations conferring ADV resistance are also found within the polymerase gene fragment amplified by the current assay. Specific mutations associated with ADV resistance are: A181T/V, Q215S and N236T.
This assay is designed to detect polymerase resistance by amplifying a 492 base pair fragment of the polymerase gene which is then sequenced and analysed for drug resistance associated mutations.
References
1. Bartholomew MM, Jansen RW, Jeffers LJ, Reddy KR, Johnson LC, Bunzendahl H, Condreay LD, Tzakis AG, Schiff ER, Brown NA. Hepatitis-B-virus resistance to lamivudine given for recurrent infection after orthotopic liver transplantation. Lancet 1997 Jan 4;349(9044):20
2. Zoulim F. Detection of hepatitis B virus resistance to antivirals. J Clin Virol. 2001 Jun;21(3):243-53. Review.
3. Angus P. et al. Resistance to Adefovir dipivoxil therapy associated with the selection of a novel mutation in the HBV polymerase. Gastroenterology 2003;125:292-297.
4. Brunelle, M et al Susceptibility to antivirals of a human HBV strain with mutations conferring resistance to both lamivudine and adefovir. Hepatology 2005 41(6):1391-1398.
For further information contact the laboratory (contact via Lablink: 22000 or (09) 307-8995 or 0800 522 7587) ,or:
the Virology team
virology@adhb.govt.nz
Separate the specimen within 4 hours and send frozen.