Adefovir rapidly suppresses hepatitis B in HBeAg‐negative patients developing genotypic resistance to lamivudine†

Abstract

Progression of hepatitis B in patients with lamivudine-resistant strains is slowed down by adefovir dipivoxil (ADV). Whether the time point of ADV administration (genotypic vs. phenotypic resistance) influences the outcome of therapy is unknown. We compared the outcome of ADV therapy in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients with genotypic and phenotypic resistance to lamivudine. Ten milligrams of ADV was administered daily for 2 years to 46 HBeAg-negative patients at the time of phenotypic resistance (group A, >6 log 10 copies/mL of hepatitis B virus [HBV] DNA and high alanine aminotransferase [ALT] levels) and 28 patients at the time of genotypic resistance (group B, 3-6 log 10 copies/mL of HBV-DNA and normal ALT). HBV DNA was assessed every 2 months using Versant 3.0 assay, and lamivudine resistance was confirmed via INNO-LiPA assay in all patients. By month 3, HBV DNA tested negative in all patients from group B compared with only 20 (46%) in group A (P < .0001). The 2-year rates of virological response were 100% in the former patients and 78% in the latter ones (P < .0001). ALT levels remained persistently normal in all group B patients, whereas in group A patients they normalized at rates of 50% at month 6 (P < .0001), 72% at month 12 (P < .01), and 93% at month 24. None of the patients developed ADV resistance or ADV-related side effects. In conclusion, to optimize antiviral treatment in HBeAg-negative patients selecting resistant strains to lamivudine, ADV should be added to lamivudine as soon as genotypic resistance is detected. (HEPATOLOGY 2005;42:1414-1419

Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B

“…Adding adefovir to ongoing lamivudine for patients who have developed lamivudine resistance has been recommended as a strategy to reduce the subsequent emergence of adefovir resistance [25,46]. This strategy is most efficacious in patients with low HBV DNA levels and requires continued resistance surveillance [47,48]. Studies evaluating the combination of entecavir with adefovir in lamivudine-resistant patients are currently in progress.…”

Efficacy and Safety of Tenofovir Disoproxil Furmarate for Patients with Lamivudine-Resistant Hepatitis B Virus Infection

“…Two patients (2.6%) among 77 HBeAg-positive patients achieved HBeAg loss at 12 are responsible for LAM resistance [7] . Adefovir dipivoxil (ADV) has an antiviral efficacy in wild-type and LAM-resistant HBV, however, suboptimal viral response is frequent [8] . ADV-resistant mutations occur more frequently in patients with LAM-resistant HBV infection than in treatment-naïve patients [9] .…”

Patterns of managing chronic hepatitis B treatment-related drug resistance: a survey of physicians in Mainland China, South Korea, Taiwan, and Thailand

“…Therefore, a key limitation of this study is the inability to differentiate between what these interviewed physicians ''believe they do'' or would ''like to do'' under ideal circumstances versus what they ''actually do'' in clinical practice. For example, a majority of the physicians expressed the desire to prevent antiviral resistance beginning with their choice of initial treatment; yet, lamivudine is the antiviral most often prescribed in these four Asian geographies despite its high resistance rate and the likelihood of developing cross-resistance with other antivirals [6,11,12]. Additional research using patient level information would enable a deeper understanding of the challenge that antiviral resistance presents in the management of CHB.…”