1. 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.

2. 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.

3. 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.

4. 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.

5. 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
( to 2.59)
-44.50
( to )
-46.00
( to )
.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 )
38.50
(-1.79 to )
.111
.034
.05
Benhamou Y, et al. J Hepatol. 2006;44:62-67.

6. 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.

7. 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.