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Significant
and Sustained Efficacy of Adefovir Dipivoxil after Four Years
of Treatment in Chronic Hepatitis B Patients with Lamivudine-Resistant
HBV and HIV Co-Infection
Adefovir/ADV (Hepsera)
has demonstrated efficacy and safety in a broad range of chronic
hepatitis B (CHB) populations, including treatment-naive and
lamivudine- (Epivir-HBV)-resistant/ LAM-R patients. The aim
of the current study was to evaluate 4 years of treatment
with ADV in HIV patients coinfected with LAM-R HBV.
ADV (10mg qd) was added to the pre-existing anti-retroviral
therapy including LAM (150 mg bid). Patients were seen every
4 weeks in the first year and every 12 weeks thereafter. At
each visit, serum HBV DNA (Roche Amplicor MonitorTM), ALT,
HBV serology, plasma HIV RNA (LLQ 2.3 log10 copies/mL)
and CD4 were assessed.
Results
Of the 35 patients enrolled in the initial one-year study,
22 have now completed 192 weeks of ADV treatment. Results
of serum HBV DNA and ALT are summarized below in Table
1.
One patient had a rebound in serum HBV DNA (³1 log10
copies/mL from treatment nadir).
No adefovir-associated mutations were identified at conserved
sites in the HBV DNA polymerase (rtN236T and rtA181V) or in
the HIV RT (K65R and K70E) for up to 144 weeks. Week 192 genotyping
is in progress.
Of 3 patients who lost HBeAg at week 48, 2 had seroconversion
(HBeAg-/anti-HBe+); seroconversion has remained durable at
week 192. No evidence of nephrotoxicity or serious adverse
events related to ADV occurred throughout 192 weeks.
HIV RNA and CD4 count remained stable.
Conclusions
Long-term treatment up to four years with ADV was well tolerated
and resulted in significant and sustained reductions in serum
HBV DNA and ALT in this ongoing study. No adefovir-associated
HBV resistance mutations have been identified up to 144 weeks.
The magnitude of reduction in serum HBV DNA and ALT continues
to increase with treatment duration.
TABLE 1
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Week 48
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Week 96
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Week 144
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Week 192
|
| |
(n=35)
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(n=30)
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(n=28)
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(n=22)***
|
|
Median Change from BL in Serum HBV DNA* (log10 copies/mL)
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-3.97**
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-4.80**
|
-5.55**
|
-5.62**
|
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HBV DNA < 1000 copies/mL
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2 (6%)
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8 (27%)
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13 (46%)
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13 (59%)
|
|
Median Serum ALT* (IU/L)
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53**
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46**
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31**
|
32**
|
|
ALT Normalization (%)
|
19%
|
37%
|
64%
|
67%
|
|
Median Change from BL in Serum ALT* (IU/L)
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-16.0 (p=0.04)
|
-44.5 (p=0.02)
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-46.0**
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-48.0**
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*
vs. baseline ** p<0.001 by Wilcoxon Signed-Rank Test
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05/17/04
Reference
Yves Benhamou and others.
Significant
and Sustained Efficacy of Adefovir Dipivoxil (ADV) After Four
Years of Treatment in Chronic Hepatitis B (CHB) Patients with
Lamivudine-Resistant (LAM-R) HBV And HIV Co-Infection. Abstract
1.
Digestive Disease Week 2004. May 15-20. New Orleans, LA.
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