A short course of add‐on adefovir dipivoxil treatment in lamivudine‐resistant chronic hepatitis B patients

Abstract

The aims of the study were to investigate the efficacy of rescue therapy with lamivudine (LAM) and adefovir (ADV) combination for 6 months followed by ADV monotherapy in lamivudine-resistant chronic hepatitis B (LAM-R CHB) patients, and to analyze the frequency of ADV resistance mutant development in such patients. A total of 170 consecutive LAM-R CHB patients (male/female: 130/ 40, mean age: 42.9 ± 13.4 years) with viral breakthrough under LAM therapy were analyzed. A total of 68 had HBeAg-positive. Patients received rescue therapy with LAM [100 mg (qd)]+ADV [10 mg (qd)] for 6 months after which LAM was discontinued. HBV-DNA was assessed with the HBV-DNA 3.0 bDNA assay. ADV-resistant mutations were identified by sequencing the reverse transcriptase region. The median duration of rescue therapy was 24 months. Cumulative probability of becoming HBV-DNA undetectable was 33.8%, 59.6% and 68.2% after 24, 48 and 96 weeks of treatment, respectively. These figures were 43.2%, 58.0% and 73.1% for ALT normalization. Among 68 HBeAg-positive CHB patients, 10 patients had an e-antigen seroconversion. Low baseline HBV-DNA level (<10 7 copies/mL) was a significant predictor of response to ADV treatment (P < 0.01). Cumulative probability of ADV resistance was 1.2%, 15.1% and 37.3% at 12, 24 and 36 months of therapy, respectively. By multivariate analysis, baseline high viral load and primary nonresponse to treatment at week 24 predicted ADV resistance. The data indicate that a time limited add-on strategy does not provide benefit over the switch strategy with respect emergence of ADV resistant mutants in LAM-R CHB patients.

British HIV Association guidelines for the management of coinfection with HIV‐1 and hepatitis B or C virus 2010

“…This also applies to nucleos(t)ide therapy where primary nonresponse is defined as a o1 log 10 IU/mL drop in HBV DNA level from baseline at 3 months, and response is defined as an undetectable HBV DNA by real-time polymerase chain reaction (PCR) assay within 48 weeks of therapy. Partial virological response is defined as a 41 log 10 IU/mL drop in HBV DNA but detectable HBV DNA by real-time PCR assay [101,102]. In HIV-uninfected patients, a partial virological response should lead to a decision about modifying therapy at 24 weeks of therapy for lamivudine and telbivudine (which have a low barrier to resistance) and at 48 weeks for entecavir, adefovir and tenofovir (which have a high barrier to resistance) [102].…”

“…Partial virological response is defined as a 41 log 10 IU/mL drop in HBV DNA but detectable HBV DNA by real-time PCR assay [101,102]. In HIV-uninfected patients, a partial virological response should lead to a decision about modifying therapy at 24 weeks of therapy for lamivudine and telbivudine (which have a low barrier to resistance) and at 48 weeks for entecavir, adefovir and tenofovir (which have a high barrier to resistance) [102]. How this should be applied in coinfected patients is uncertain.…”

“…defined as a confirmed increase of 41 log 10 IU/mL above nadir HBV DNA level on therapy, means either nonadherence or resistance [102]. The lower limit of detection of the assays used to monitor HBV DNA should be 10-15 IU/mL and this level should also be the aim of treatment [103].…”

“…The ideal outcome of treatment is HBe seroconversion in patients who are HBeAg positive and HBs seroconversion (very rare) in all patients [102]. Once HBV DNA is undetectable, HBeAg and eAb in HBeAg-positive patients and HBsAg in all patients should be tested every 12-24 weeks to pick up seroconversion.…”

“…It should be noted that there is no HBV DNA level at which seroconversion from HBeAg positive to negative is completely predictable [105]. Spontaneous or treatment-induced seroconversion from HBsAg positive to negative is associated with ongoing undetectable HBV DNA but, in patients who convert from HBeAg positive to negative, HBV DNA may still be detectable at low levels [102,106].…”