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发表于 2003-1-4 23:57
| Viread (Tenofovir) Expands Hepatitis B Treatment Options
By Mark Nelson, MD, and Brian Boyle, MD
August 2, 2002
Treatment of HBV would normally entail interferon or Epivir-HBV (lamivudine,
3TC) or a combination of the two. There are several advantages and
disadvantages to each of these approaches. The use of interferon is often
difficult due to the associated side-effects, whilst the usage of Epivir-HBV
is associated with increasing reports of viral resistance which may be as
high as >90 % at 4 years. New treatment modalities include the
pegylated-interferons, adefovir and Viread (tenofovir).
There were several reports at this conference regarding the use of Viread
for the treatment of HBV. Nelson (the author of this article) and colleagues
reported their experience at the Chelsea & Westminster Hospital with Viread in the treatment of co-infected individuals with HBV.
Twenty individuals, 15 with previous exposure to Epivir-HBV and with
evidence of HBV virological failure, were recruited to add or substitute Viread into their antiviral regimen. All 15 patients who had virological failure with Epivir-HBV continued this drug. Median ALT was 100 (range 20-386) IU/L and baseline HBV viral load was 5.8 x 108 (range 9.4 x 104-1.5 x 1010) copies/mL.
Reductions in HBV viral load and total suppression rates of the virus are
illustrated in Figures 1 and 2 below. By 24 weeks, 2 patients had
seroconverted from Hepatitis B e antigen (HBeAg) positive to e antibody
(HBeAb) positive.
Cooper and colleagues presented data on individuals enrolled in Gilead study 907 who were co-infected with HBV. Study 907 was a double-blind,
placebo-controlled trial of Viread once daily added to stable, but failing,
ARV therapy. Twelve individuals, 10 who received Viread and 2 placebo, were co-infected. All of the patients were male and the median serum HBV DNA was 8.69 log10 copies /mL and serum ALT prior to therapy was 81.5 IU/L. Eleven of the 12 patients were confirmed HBeAg positive and one patient had this data missing; all were Epivir-HBV experienced.
Genotypic analysis at baseline confirmed that 7 harboured mutations typical of Epivir-HBV resistance (i.e., the YMDD motif), whilst 5 had wild type virus.
After 24 weeks of therapy, the median change in serum HBV DNA from baseline
was -4.44 and -1.23 log10 copies/mL for the Viread and placebo receiving
patients, respectively. (P=0.04) This reduction was sustained to week 48,
with almost a 5 log10 copies/mL decrease at that point in the Viread
recipients. HBV DNA changes did not differ between those individuals who
had wild-type or confirmed Epivir-HBV resistance at baseline. At week 48, ALT had decreased from baseline by a median of 30 IU/L, but only 2 patients normalised their ALT. HBeAg seroconversion was observed in one individual receiving Viread.
Tubiana and associates reported their experience with Viread in Epivir-HBV
resistant individuals. Eleven individuals who were serum HBV DNA positive
and receiving Epivir 150mg twice daily as part of their current HIV
antiretroviral regimen had Viread 300mg once a day added to their current Epivir-containing regimen. All of the patients had HBV with confirmed Epivir-HBV resistance (i.e., the YMDD mutation), and 10 out of 11 were HBeAg positive. Median ALT at baseline was 80 IU/L. The median changes in serum HBV DNA concentration from baseline were -2.23, -2.27, -3.11 and -3.67 log10 copies/mL at weeks 4, 8, 12 and 16, respectively. There were no significant changes in mean serum ALT from baseline.
Dieterich and colleagues reported on 22 HIV/HBV co infected males who were receiving Epivir (150mg twice daily) and famciclovir (500mg twice daily) as part of their antiviral therapy. [B10533] These individuals had Viread 300mg once daily added to their antiretroviral therapy. Only 9 of the 22 patients were HBV DNA positive at the time of the addition of Viread. This led to a median increase in CD4+ T cell count from baseline of 78 cells/mm3 at week 8 and a decrease in HIV RNA from baseline of -2.33 log10 copies/mL at week 4 and -2.27 log10 copies/mL at week 8. Serum HBV DNA decreased compared to baseline by 2.86 log10 copies/mL at week 4, and 3.8 log10 copies/mL at week 8.
Two patients achieved HBV DNA levels of < 200 copies/mL at week 8. Again, there were no significant changes in mean AST or ALT.
Taken together these reports indicate that Viread has excellent activity
against HBV and that it is very well tolerated; in no individual was a grade
3 or 4 toxicity found as a result of the addition of Viread. The best
positioning of Viread in anti-HIV therapy will clearly be influenced by
whether a patient is HIV/HBV co-infected. Whether these individuals should
receive both Viread and Epivir or one in preference to the other is a matter
of ongoing clinical trials.
The failure to normalize ALT/AST is probably related to toxicity from other
antiviral agents, other drugs and other disease processes occurring in these individuals and not due to a potency problem with Viread.
08/02/02
References
M Nelson and others. Tenofovir in the treatment of individuals co-infected
with HIV and hepatitis B. Abstract B7302. Program and Abstracts of the XIV
International AIDS Conference. July 7-12, 2002. Barcelona, Spain.
D Cooper and others. Anti-Hepatitis B Virus (HBV) activity of Tenofovir
Disoproxil Fumarate (TDF) in Lamivudine (LAM) experienced HIV/HBV
co-infected
patients. Abstract B6015. Program and Abstracts of the XIV International
AIDS
Conference. July 7-12, 2002. Barcelona, Spain.
R Tubiana. Tenofovir Disoproxil Fumarate (TDF) suppresses
Lamivudine-Resistant
HBV replication in patients co-infected with HIV/HBV. Abstract C7527.
Program and Abstracts of the XIV International AIDS Conference. July 7-12,
2002.Barcelona, Spain.
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Z网友在本论坛英文版也曾经等出国这则消息)
