Adefovir Suppresses HBV DNA Levels in Lamivudine-Resistant HIV/HBV Patients Slideset on: Benhamou Y, Thibault V, Vig P, et al. Safety and efficacy of adefovir dipivoxil in patients infected with lamivudine-resistant hepatitis B and HIV-1. J Hepatol. 2006;44:62-67.

Background 5% to 10% of HIV-infected individuals coinfected with HBV HIV-related immunosuppression increases HBV replication HIV/HBV coinfection increases chronic liver disease risk Lamivudine lowers HBV levels in HIV/HBV-coinfected patients, but HBV resistance to lamivudine common Results in viral rebound and progressive liver disease Adefovir previously shown to significantly improve clinical outcomes for lamivudine-resistant HBV patients Current study assessed safety and efficacy of adefovir in HIV/HBV-coinfected patients with HBV lamivudine resistance Benhamou Y, et al. J Hepatol. 2006;44:62-67.

Study Design Prospective, open-label pilot study Subset of patients enrolled in 48-week studies continued adefovir 10 mg/day for an additional 96 weeks in addition to lamivudine Inclusion criteria of original studies HIV/HBV coinfection Detectable HBV DNA ≥ 6 months prior to enrollment YMDD mutation in HBV polymerase gene Patients evaluated at 12-week intervals from Week 48 to Week 144 Benhamou Y, et al. J Hepatol. 2006;44:62-67.

Summary of Main Findings Total of 29 patients completed 144 weeks of adefovir therapy Patient responses for HBV DNA suppression, ALT normalization, and CD4+ cell count generally improved with increasing duration of adefovir therapy At 144 weeks 7 patients (25%) had HBV DNA < 2.3 log10 copies/mL 13 patients (37%) had HBV DNA < 3.0 log10 copies/mL HIV-1 RNA suppression remained unchanged Benhamou Y, et al. J Hepatol. 2006;44:62-67.

Main Findings Outcome, as Compared With Baseline Week 48 Week 96 HBV DNA Median change, log10 copies/mL (95% CI) -4.67 (-5.02 to -3.81) -5.47 (-5.91 to -4.90) -5.90 (-7.12 to -5.26) P value < .001 ALT Median change, IU/L (95% CI) -16.00 (-55.75 to 2.59) -44.50 (-73.36 to -14.11) -46.00 (-83.81 to -14.19) .04 .0023 < .0001 Normalization, % 14 48 68 .042 .002 CD4+ cell count Median change, cells/mm3 (95% CI) 30.00 (-1.58 to 99.71) 45.00 (5.54 to 110.74) 38.50 (-1.79 to 123.79) .111 .034 .05 Benhamou Y, et al. J Hepatol. 2006;44:62-67.

Other Outcomes No HBV adefovir resistance mutations (ie, N236T, A181V) observed in any patients with measurable HBV DNA No HIV-1 adefovir resistance mutations (ie, K65R, K70E) observed in any patients with measurable HIV-1 RNA Adefovir generally well tolerated with no report of any serious adverse events related to treatment Most common adverse event involved mild asthenia Benhamou Y, et al. J Hepatol. 2006;44:62-67.

Key Conclusions HIV/HBV-coinfected patients with lamivudine resistance receiving adefovir plus ongoing lamivudine for 144 weeks had significant and sustained reductions in HBV DNA and ALT levels Magnitude of viral and ALT suppression increased in accord with treatment duration No adefovir resistance mutations observed in either HBV polymerase or HIV-1 reverse transcriptase No grade 3/4 adverse events related to adefovir treatment reported Benhamou Y, et al. J Hepatol. 2006;44:62-67.