Presentations in Hepatology

16 Jul
2010

Manns and colleagues presented results of a pooled analysis evaluating the efficacy of tenofovir disoproxil fumarate (TDF; Viread, Gilead) in patients with suboptimal response to adefovir dipivoxil (ADV; Hepsera, Gilead). The analysis included patients enrolled across 3 clinical trials: Study 102 (in hepatitis B e antigen [HBeAg]-neg-ative patients), Study 103 (in HBeAg-positive patients), and Study 106 (in ADV-refractory chronic hepatitis B patients). The current analysis focused on patients with a suboptimal response to ADV, defined as 48 weeks of ADV exposure prior to enrolling in Studies 102 and 103 with a hepatitis B virus (HBV) DNA level of at least 69 IU/mL (>400 copies/mL) or with 24-96 weeks of

ADV exposure in Study 106 with an HBV DNA level of at least 172 IU/mL (>1,000 copies/mL). Of the 160 patients evaluated, 65% were HBeAg-positive; 54% were white, and 34% were Asian; the mean HBV DNA level was 7.66 log10 copies/mL; and the mean alanine aminotransferase (ALT) was 122.4 U/L. Mean prior ADV duration was 53 weeks; 23% of patients had received prior lamivudine (LAM). Resistance to ADV and LAM was detected in 7.5% and 4.4% of patients, respectively. At Week 96 after starting TDF, viral suppression was attained by 75% of patients without ADV or LAM resistance, 10 of 12 (83%) patients with ADV resistance, and 6 of 7 patients (86%) with LAM resistance, in a missing/switch=failure analysis. Mean ALT at Week 96 in these subgroups was 39 U/L, 31 U/L, and 25 U/L, respectively. The overall median HBV DNA level was 29 IU/mL (169 copies/mL). HBeAg loss occurred in 10% of patients by Year 1 and 15% by Year 2. HBeAg seroconversion occurred in 7% and 10% of patients, respectively. In regard to safety, TDF-related serious adverse events occurred in 2 patients (1.3%) and grade 3/4 laboratory abnormalities were reported in 13.8%. No patients discontinued therapy due to adverse events. Although 34 patients had HBV DNA levels greater than 400 copies/mL (>69 IU/mL) after receiving up to 96 weeks of TDF, no TDF-associated resistance was detected.
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