Overview of Antiretroviral Therapy for Patients with HIV-HBV Coinfection Due
to similar transmission routes, coinfection with HIV and hepatitis B virus (HBV)
is common worldwide. In the U.S. and Europe, it is estimated that more than half
of HIV positive men who have sex with men have evidence of past HBV infection,
and 7%-10% have chronic hepatitis B. In
the October 11, 2006 issue of Clinical Infectious Diseases, Vivian Levy
from Stanford University and Robert Grant from the University of California at
San Francisco presented an overview of the natural history and treatment of hepatitis
B in HIV-HBV coinfected patients. "HIV
infection modifies the course of HBV infection by increasing rates of chronicity,
prolonging HBV viremia, and increasing liver-related morbidity," they wrote.
HIV-infected
adults with acute HBV infection are less likely to eliminate the virus compared
with HIV negative adults (23% vs 4%). Without hepatitis B treatment, HIV-HBV coinfected
patients have higher HBV DNA levels and a longer duration of viremia, but may
have lower transaminase (liver enzyme) levels compared with HBV monoinfected patients.
HIV-HBV coinfected individuals also have a higher rate of liver-related morbidity
than persons with either virus alone. Treatment
for hepatitis B is indicated for patients with evidence of progressive liver disease.
The currently approved therapies are lamivudine (Epivir-HBV),
adefovir (Hepsera), entecavir
(Baraclude), conventional
interferon, and pegylated interferon-alpha
2a (Pegasys). Tenofovir DF (Viread) and emtricitabine
(Emtriva) are currently under study as therapies for HBV. As
is the case with HIV, treatment for HBV is limited by the emergence of drug-resistant
virus. However, nucleotide analogs (adefovir and tenofovir) appear to select for
HBV resistance less commonly than nucleoside analogs (lamivudine and emtricitabine). "Lamivudine
or emtricitabine monotherapy readily selects resistant strains in the YMDD motif
of the polymerase gene," the authors wrote. "Adefovir monotherapy has
moderate effectiveness in HIV-HBV coinfected patients who have YMDD mutations." Lamivudine,
adefovir, tenofovir, and emtricitabine all have activity against both HBV and
HIV. When any of these drugs are discontinued in a patient with hepatitis B, sudden
increases in liver enzymes ("flares") may occur. "To
minimize the emergence of HIV and/or HBV resistance, as well as the emergence
of liver enzyme flares, the treatment of both infections should be coordinated,"
according to Levy and Grant. Whether
to treat hepatitis B in coinfected patients -- and whether HIV or HBV should be
treated first -- is an individualized decision based on a variety of factors,
including the need for combination antiretroviral therapy for HIV, severity of
liver disease, likelihood of treatment response, and potential adverse events.
Since coinfected patients tend to experience more rapid liver disease progression
than those with HBV alone, regular monitoring of liver fibrosis is indicated. "Although
clear evidence is lacking that suppression of HBV replication before the commencement
of combination antiretroviral therapy prevents immune reconstitution flares,"
the authors wrote, "we concur with others who recommend using combination
therapy with lamivudine (or emtricitabine) and tenofovir in the combination antiretroviral
regimen for all HIV-HBV coinfected patients with active HBV replication, especially
those with cirrhosis."
They continued, "If HBV treatment can
be deferred until combination antiretroviral therapy for HIV infection is needed,
the combination of tenofovir plus lamivudine or emtricitabine provides potent
HBV therapy and a solid backbone for HIV combination antiretroviral therapy, and
it likely decreases the emergence of HBV resistance." 10/10/06 Reference
V
Levy, R M Grant. Antiretroviral Therapy for Hepatitis B Virus-HIV-Coinfected Patients:
Promises and Pitfalls. Clinical Infectious Diseases 43(7): 904-910. October
1, 2006. | 
