of HIV Positive Patients with Chronic Hepatitis B Who Are Not Eligible for Antiretroviral
are limited data on how best to treat chronic
hepatitis B patients coinfected with HIV. The issue is complicated by the
fact that some agents used to treat hepatitis B
and some antiretroviral drugs for
HIV are active against both viruses, and using them inappropriately can lead
to drug resistance.
entecavir (Baraclude) has been recommended
for the treatment of hepatitis B in coinfected patients who did not require antiretroviral
therapy. Recently, however, it was demonstrated that entecavir
does have anti-HIV activity and can promote emergence of drug-resistant HIV.
Sasadeusz and colleagues have recommended avoiding entecavir as a single agent
for chronic hepatitis B in HIV-HBV coinfected patients . Their findings reflect
those of other recent reports concerning entecavir use in the treatment of chronic
hepatitis B in HIV-infected patients . They showed the significant anti-HIV
effect of entecavir and its ability to select for the M184V lamivudine-resistant
mutation in HIV [1,2].
a letter to the editor published in the November 30, 2008 issue of AIDS,
French researchers noted a drop in HIV viral load and the selection of the M184V
mutation during entecavir monotherapy in 4 HIV positive men. These patients had
HBeAg positive chronic hepatitis B and did not require combination antiretroviral
therapy, according to recent guidelines .
are edited excerpts from the French group's report:
At baseline the patients had a median age of 41 years, a median HBV DNA level
of 7.2 log10 IU/mL, and a median HIV RNA level of 3.6 log10 copies/mL.
2 patients were naive to lamivudine
(Epivir-HBV) and 2 were lamivudine-experienced; the latter 2 patients started
lamivudine prior to acquiring HIV infection.
The median duration of entecavir monotherapy was 12 months and the median change
in HBV DNA from baseline was -4.4 log10 IU/mL.
The median change in HIV viral load was -0.33 log10 copies/mL.
2 patients (1 lamivudine-experienced and 1 naive) acquired the M184V mutation
at months 9 and 10, respectively.
From baseline, these 2 patients had HIV viral load changes of -0.89 and -0.51
log10 copies/mL, respectively.
Sasadeusz and colleagues , the French researchers recommended avoiding entecavir
as a single agent for chronic hepatitis B in HIV-HBV coinfected patients.
then should clinicians manage chronic hepatitis B in patients who do not require
According to guidelines from the European AIDS Clinical
Society (EACS) , the 4 French patients should have received HBV therapy based
on 3 of them having an HBV DNA level greater than 6.0 log10 IU/mL and Metavir
fibrosis score greater than F3. However, they did not require antiretroviral therapy
because of high CD4 cell counts (547-1033 cells/mm3) and low HIV viral load (3.0-4.2
log10 copies/mL), wrote the French authors.
"In patients with a CD4
cell count less than 500 [cells/mm3]," they continued, "the best option,
according to current recommendations, is to consider earlier initiation of combination
antiretroviral therapy, including 2 drugs with dual anti-HBV and HIV activity."
Along these lines, the current U.S.
antiretroviral therapy guidelines recommend that all HIV-HBV coinfected patients
who require treatment for hepatitis B should receive a full HAART regimen that
includes dually active agents.
However, the French authors stated, "Recommending
the same strategy in patients with CD4 cell counts greater than 500 cells/[cells/mm3]
is questionable," especially if their HIV viral load is less than 100,000
interferon (Pegasys or PegIntron) may be an option for HBeAg positive patients
with HBV genotype A, elevated alanine transaminase (ALT), and/or low HBV DNA,
according to the EACS guidelines .
But unlike HBV monoinfection, data
on the use of pegylated interferon in HIV-HBV coinfected patients are scarce,
according to the authors.
"Two of our patients were placed on pegylated
interferon alfa-2a [Pegasys] before initiation of entecavir," they wrote.
"Pegylated interferon was discontinued after 7 months in one patient because
of depression. The other patient was treated with pegylated interferon for 48
weeks and achieved HBeAg seroconversion upon treatment, which was not sustained
after treatment discontinuation."
Regarding the use of 10 mg adefovir
(Hepsera) for hepatitis B treatment, there is a theoretical risk of inducing
HIV resistance mutations. (A higher dose of adefovir was once studied as an anti-HIV
drug, but was abandoned due to toxicity concerns.)
"Recent data suggest
that this risk is negligible," wrote the authors . Still, they emphasized,
"Adefovir should not be used alone." They cited data from studies of
HBV monoinfected patients showing that the risk of selecting an HBV resistance
mutation when using adefovir monotherapy reaches 29% by year 5 .
(Tyzeka) could also be considered , although the authors acknowledged that,
"The absence of [telbivudine] anti-HIV activity remains to be confirmed."
In contrast to EACS guidelines, the French authors believe that telbivudine
should not be used as monotherapy, because in HBV monoinfected patients the risk
of HBV resistance mutations is 18% in HBeAg positive and 7% in HBeAg negative
patients at year 2 [7,8].
"One acceptable option may be the use of
an adefovir-telbivudine combination in these patients," the authors suggested.
conclusion, the authors wrote, "Entecavir monotherapy should be avoided in
HBV-HIV coinfected patients. In those who are not eligible for combination antiretroviral
therapy, earlier initiation of combination antiretroviral therapy, which includes
two drugs with dual activity against HBV and HIV, can be considered."
strategy is, however, questionable in patients with CD4 cell counts more than
500 [cells/mm3], and especially in those patients with low HIV viral load and
no other comorbidities where pegylated interferon or a combination of potent nucleos(t)ide
analogues such as adefovir and telbivudine may be of interest. Additional data
concerning the safety of this combination are needed."
des Maladies Infectieuses et du Voyageur, CH de Tourcoing, Tourcoing, France;
Laboratoire de Virologie, CHRU de Lille, Lille, France ; Laboratoire de Virologie,
Centre Hospitalier de La Timone, France ; Service d'Hépatologie, Hôpital
Saint-Joseph, Marseille, France.
on Entecavir at AASLD 2008
Articles on Entecavir Posted on HIV and Hepatitis.com
Castel, L Bocket, C Tamalet, and others. How should chronic hepatitis B virus
infection be managed in HIV-hepatitis B virus-coinfected patients not eligible
for concomitant antiretroviral therapy? [Correspondence]. AIDS 22(18):
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J Sasadeusz and others. The anti-HIV activity of entecavir: a multicentre evaluation
of lamivudine-naive patients. AIDS 22: 947-955. 2008.
MA MacMahon and others. The HBV drug entecavir effects on HIV-1 replication and
resistance. New England Journal of Medicine 356: 2641-2721. 2007.
N Clumeck and others (EACS Executive Committee). European AIDS Clinical Society
(EACS) guidelines for the clinical management and treatment of HIV-infected adults.
HIV Medicine 9: 65-71. 2008.
JA Sheldon and others. Risk of selecting K65R in antiretroviral-naive HIV-infected
individuals with chronic hepatitis B treated with adefovir. AIDS 9: 2036-2038.
5. S Locarnini
and others. Incidence and predictors of emergence of adefovir resistant HBV during
four years of adefovir dipivoxil (ADV) therapy for patients with chronic hepatitis
B (CHB). Journal of Hepatology 42: A36. 2005
CL Lai and others. Two-year results from the GLOBE trial in patients with hepatitis
B: greater clinical and antiviral efficacy for telbivudine (LdT) vs. lamivudine.
Hepatology 44(S1): 222A. 2006.
DN Standring and others. HBV resistance determination from the telbivudine GLOBE
registration trial. Journal of Hepatology 44(Suppl 2): S191. 2006.
SJ Matthews. Telbivudine for the management of chronic hepatitis B virus infection.
Clinical Therapy 29: 2635-2653. 2007.
/ Nucleotide Reverse Transcriptase Inhibitors
(including Fusion Inhibitors)
(efavirenz + emtricitabine + tenofovir) Combivir
(zidovudine + lamivudine)Trizivir
(abacavir + zidovudine + lamivudine)Truvada
(tenofovir + emtricitabine)|