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ADEFOVIR TREATMENT OF PATIENTS WITH LAMIVUDINE RESISTANCE: PREDICTIVE ROLE OF EARLY VIRAL KINETICS
S Pritchett, D Wong, C Yim, T Mazzuli, EJ Heathcote
BACKGROUND: Adefovir (ADV) is currently the drug of choice for treatment of Lamivudine-resistant (LAM-R) chronic Hepatitis B (CHB). However, ADV may not always suppress HBV in this setting.
AIMS: To identify factors that predict adequate i.e. undetectable HBV DNA (<60 IU/mL) response to ADV in the treatment of LAM-R CHB.
METHODS: A retrospective study of CHB with genotypic or phenotypic LAM-R treated with ADV 10mg daily in an Add To or Switch To/Add Back Lam treatment strategy. Adequate response to ADV was defined as undetectable HBV DNA (<200copies/mL or <60IU/mL) at 1 yr. Factors evaluated included HBeAg status, treatment strategy, baseline (just prior to starting ADV) HBV DNA level, whether ADV was added at phenotypic or genotypic resistance, and rapid HBV DNA decline at 6 months, defined as >50% logarithmic decline from baseline HBV DNA. A multivariate analysis was performed both for all patients and for the subset with cirrhosis.
RESULTS: Only 45 of 95 (47%) patients achieved undetectable HBV DNA at 1 yr. In multivariate analysis, only baseline HBV DNA level and >50% log decline in HBV DNA at 6 months predicted achieving undetectable HBV DNA at 1 yr. Although patients with a baseline HBV DNA >7 log IU/mL were only 12% (95% CI: 3% to 43%) as likely to achieve an undetectable HBV DNA at 1 yr compared to patients with HBV DNA <7 log IU/mL, this effect continued above and below this cutoff. For each 1 log IU/mL increase in baseline HBV DNA a patient was only 40% (95% CI: 25% to 64%) as likely to attain an undetectable HBV DNA at 1 yr. Patients who at 6 months had >50% logarithmic decline in baseline HBV DNA were 25.4 (95% CI: 3.1 to 206.1) times more likely to reach undetectability at 1 yr. These same factors significantly predicted response at 1 yr even when only patients with cirrhosis were evaluated. Of the 4 patients with ADV resistance up to 1 year, 3 were patients with a <50% log decline in baseline HBV DNA at 6 months.
CONCLUSIONS: ADV should be started at the first emergence of LAM-R when HBV DNA is lowest to maximize the probability of achieving an adequate response. As ADV resistance was only observed in patients who’s HBV DNA did not decline by >50% by 6 months, this may be the optimal time to change anti-viral therapy.