835 
3-Year Treatment with Adefovir Dipivoxil in Chronic Hepatitis B Patients with Lamivudine-resistant HBV/HIV Co-infection, Results in Significant and Sustained Clinical Improvement
Y Benhamou*1, V Thibault1, V Calvez1, P Vig2, M A Valantin1, P Guyon1, C Katlama1, B Lu2, C G Chang2, G Currie2, C L Brosgart2, and T Poynard1
1Hosp. Pitié-Salpêtrière, Paris, France and 2Gilead Sci., Inc., Foster City, CA, USA
Background: Adefovir dipivoxil (ADV), 10 mg, has shown efficacy and safety in a
broad range of populations with chronic hepatitis B over 48 to 96 weeks,
including treatment-naive and Lamivudine-resistant (LAM-R) HBV patients. This
study reports the first 3-year long-term safety and efficacy data with ADV in patients with LAM-R HBV, co-infected with
HIV.
Methods:
Patients failing LAM received 3 years of ADV
added to pre-existing anti-retroviral therapy including LAM. Patients were seen
every 4 weeks for 48 weeks and then every 12 weeks. At each visit, serum ALT, serum HBV DNA
(Roche Amplicor PCR), HBV
serological markers, plasma HIV RNA (Roche HIV Monitor LLQ 2.3 log10
copies/mL) and CD4 count were evaluated.
Results:
Of the 35 patients enrolled, 28 completed
144 weeks of ADV. Median serum HBV
DNA declined from baseline 8.75
(Q1-Q3, 8.41 to 8.93) log10 copies/mL by 3.98 (3.48 to 4.79), 4.81
(3.86 to 5.31), and 5.45 (3.94 to 6.15) log10
copies/mL at weeks 48, 96, and 144, respectively (p <0.0001). Thirteen patients (46%) achieved undetectable serum
HBV DNA levels (£ 3 log10 copies/mL) at week 144. In 3 patients
cessation of lamivudine had no effect on HBV DNA
levels. One patient had a rebound in serum HBV DNA
(confirmed ³1 log10 copies/mL
increase from nadir) while on ADV
therapy. No HBV or HIV resistance mutations associated with ADV were identified up to week 96. Week 144
resistance surveillance is ongoing. Median ALT
was reduced by 16, 44.5, and 46 IU/L and ALT
normalized in 19%, 37%, and 64% after 48, 96 and 144 weeks, respectively. No
serious adverse events related to ADV
occurred throughout the study period and there were no significant changes in
HIV RNA throughout the study. No serum creatinine elevations related to ADV were seen. CD4 cell counts and serum HIV RNA
levels remained stable throughout the study
Conclusions: Long-term treatment
with ADV (10 mg once daily) was
well tolerated and resulted in significant and sustained reduction in serum HBV
DNA and ALT
over 3 years of therapy, with the magnitude increasing with treatment duration
and there was no loss of suppression. No HBV- or HIV-resistance mutations
associated to ADV were identified.
Keywords: Adefovir Dipivoxil; HBV and HIV Co-Infection; Lamivudine-resistant
