Addition
of Emtricitabine (Emtriva) Does Not Improve Response to Tenofovir (Viread) for
Chronic Hepatitis B By
Liz Highleyman
The
U.S. Food and Drug Administration approved tenofovir
(Viread) for the treatment
of chronic hepatitis B virus (HBV) infection in August 2008. Tenofovir
is also active against HIV, and is a component of 2 widely used fixed-dose
combination pills, Truvada (tenofovir/emtricitabine)
and Atripla (tenofovir/emtricitabine/efavirenz).
Emtricitabine (Emtriva) is structurally
related to lamivudine (3TC, Epivir).
Like tenofovir, these drugs are also active against both HBV
and HIV; lamivudine is approved for both
diseases, while emtricitabine at this time is only approved for HIV. As
described in a poster presented at the 44th Annual Meeting
of the European Association for the Study of the Liver (EASL 2009) last month
in Copenhagen, T. Berg and an international team of colleagues conducted Study
106, comparing the efficacy of tenofovir/emtricitabine combination therapy versus
tenofovir alone for the treatment of chronic hepatitis B.
The study included
105 chronic hepatitis B patients who had an incomplete virological response after
receiving adefovir (Hepsera) for
at least 24 but less than 96 weeks (mean of about 60 weeks); HBV viral load was
at least 1000 copies/mL. Most were men, about 40% each were Asian and white, and
the mean age was about 40 years; about 75% were hepatitis B "e" antigen
(HBeAg) positive. Patients with HIV
or hepatitis C virus (HCV) coinfection were not included.
About 60%
of the participants had at least 1 year of prior lamivudine experience. Sequencing
of baseline HBV genetic sequences showed that 13 patients had pre-existing lamivudine-associated
resistance mutations and 10 had adefovir-associated resistance mutations.
Participants
were randomly assigned to receive either 300 mg tenofovir plus 200 mg emtricitabine
once-daily using the Truvada pill or 300 mg once-daily tenofovir monotherapy.
Patients in both treatment arms could switch to open-label tenofovir/emtricitabine
after 24 weeks if they had persistent HBV viral load greater than 400 copies/mL.
Intention-to-treat analyses were conducted using both non-completer =
failure (NC=F) and non-completer or switch = failure (NC/S=F) criteria.
Results
9 patients in the tenofovir/emtricitabine arm and 16 in the tenofovir monotherapy
arm switched to open-label tenofovir/emtricitabine due to persistent viremia at
week 24.
At 96 weeks, in the NC=F analysis, 83% of patients originally assigned to the
tenofovir/emtricitabine arm and 89% originally assigned to tenofovir monotherapy
achieved HBV DNA < 400 copies/mL, not a statistically significant difference
(P = 0.52).
In the NC/S=F analysis, 75% of patients assigned to tenofovir/emtricitabine and
68% assigned to tenofovir alone achieved HBV DNA < 400 copies/mL, again not
a significant difference (P = 0.41).
Among patients with pre-existing adefovir resistance mutations, 100% in the tenofovir/emtricitabine
arm and 88% in the tenofovir monotherapy arm achieved HBV DNA < 400 copies/mL.
Among patients with pre-existing lamivudine resistance mutations, 100% in both
treatment arms achieved undetectable HBV DNA.
ALT was within normal limits in 77% of patients in the tenofovir/emtricitabine
arm and 65% in the tenofovir monotherapy arm.
15% of patients in the combination therapy arm and 13% in the tenofovir monotherapy
arm achieved HBeAg loss.
13% and 8%, respectively, experienced HBeAg seroconversion.
4% of patients in the tenofovir monotherapy arm -- but none in the combination
arm -- achieved hepatitis B surface antigen (HBsAg) loss.
For HBsAg seroconversion, the corresponding figures were 2% and none.
Combination therapy and tenofovir monotherapy were both well tolerated, with no
discontinuations due to adverse events.
15% of patients in the tenofovir/emtricitabine arm and 8% in the tenofovir monotherapy
arm experienced serious adverse events, but none were considered drug-related.
No serious kidney-related events were observed in either arm.
Based
on these findings, the investigators concluded, "Both treatment strategies
[tenofovir monotherapy and tenofovir/emtricitabine]…were equivalent through
96 weeks of follow-up in this heavily pretreated, highly viremic population."
They
continued, "There is a non significant trend favoring combination [therapy]
for antiviral efficacy when considering subjects who added [emtricitabine] or
switched from blinded [emtricitabine/tenofovir] to open-label as failures."
Finally,
they noted, "Virologic response was independent of pre-existing adefovir
or lamivudine-associated mutations."
Medizinische Klinik mit Schwerpunkt
Hepatologie & Gastroenterologie, Charite Campus Virchow-Klinikum; Praxis Dr.
Möller, Berlin, Germany; San Jose Gastroenterology, San Jose, CA; Office
of Sing Chan, MD, Flushing, NY; Hopital Beaujon, Clichy, France; Hospital Universitario
de Valme, Sevilla, Spain; Gilead Sciences, Durham, NC.
5/05/09 References
T
Berg, B Moller, H Trinh, and others. Tenofovir disoproxil fumarate (TDF) versus
emtricitabine plus TDF (FTC/TDF) for treatment of chronic hepatitis B (CHB) in
patients with persistent viral replication receiving adefovir dipivoxil. 44th
Annual Meeting of the European Association for the Study of the Liver (EASL 2009).
Copenhagen, Denmark. April 22-26, 2009. Abstract 903.
Evolution of Viral
Load and Genome Sequence in a Clinical Trial of Tenofovir/Emtricitabine Combination
versus Tenofovir Monotherapy for Patients with Previous Adefovir Dipivoxil Failure.
EASL 2009). Copenhagen, Denmark. April 22-26, 2009. EASL
2009 MAIN PAGE
EASL
2009 Conference Coverage
HIV and Hepatitis.com Highlights from EASL 2009
15th
Conference on Retroviruses and Opportunistic Infections (CROI 2009)
Coverage
by HIV and Hepatitis.com - February 8 - 11, 2009, Montreal
HIV and AIDS Treatment
News, Experimental News, FDA-approved News Highlights
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- Coverage by HIV and Hepatitis.com, February 8 - 11, 2009, Montreal
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