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Combination Therapy in HBV: will it improve response?
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"Ninety-Six--Week Efficacy of Combination Therapy with Lamivudine and Tenofovir in Patients Coinfected with HIV-1 and Wild-Type Hepatitis B Virus"
Clinical Infectious Diseases Oct 2004;39:1062-1064
F. Bani-Sadr,1a P. Palmer,2 C. Scieux,2 and J. M. Molina1
1Service des Maladies Infectieuses et Tropicales and 2Laboratoire de Virologie, Hôpital Saint Louis, Paris, France
ABSTRACT: We describe 6 patients who were coinfected with human immunodeficiency virus (HIV) type 1 and wild-type hepatitis B virus (HBV), in whom complete and sustained antiviral activity against wild-type HBV strains was attained during 96 weeks of combination therapy with lamivudine and tenofovir. The use of combination therapy with lamivudine and tenofovir for the treatment of HBV infection is very 'promising' in the treatment of HIV/HBV coinfection.
Note from Jules Levin: There has been very little study data of combination therapy for HBV. This study is small & not controlled but there is hope that combination therapy will be more successful, yet it has not been established or studied. Here are two studies that have been conducted with combination therapy. This first shows no benefit combining LDT+Lamivudine, except a reduction in lamivudine resistance:
http://www.natap.org/2004/EASL/easl_10.htm
This study looks at Pegasys+lamivudine:
http://www.natap.org/2004/HBV/091604_01.htm
And this is a review of the Medical Management of HBV, noting that in the author's opinion combination therapy will be the way to approach treatment but research hasn't identified a combination yet:
http://www.natap.org/2004/HBV/092004_05.htm
ARTICLE TEXT
The main goal of the treatment of hepatitis B virus (HBV) infection is the sustained suppression of HBV replication, because suppression is associated with a normalization of transaminase levels and improvement in histologic findings. Lamivudine inhibits HBV replication in >80% of HIV/HBV--coinfected patients. However, HBV resistance to lamivudine is seen in 50% and 90% of patients after 2 and 4 years of continuous therapy, respectively. Therefore, the use of combination therapy should be more effective than the use of monotherapy in reducing the viral load and in decreasing the emergence of resistance. Tenofovir is a nucleotide reverse-transcriptase inhibitor with excellent activity in vitro and in vivo against wild-type HBV and lamivudine-resistant HBV. In the present pilot study, we prospectively evaluated the long-term anti-HBV activity of the combination of lamivudine and tenofovir as part of HAART for all HIV-1--infected patients who were chronically coinfected with wild-type HBV and who were followed during treatment at our institution from May 2001 through January 2002.
Five men and 1 woman with a median age of 44 years were included in the study. One patient was a former injection drug user, and 5 had acquired HIV infection and HBV infection through homosexual contacts. One patient was also anti-HCV positive. Four patients had Centers for Disease Control and Prevention (CDC; Atlanta, GA) HIV stage C disease. One patient presented with jaundice and ascites. At baseline, the median CD4 lymphocyte count was 56 cells/mm3 (range, 31--260 cells/mm3), and the median plasma HIV RNA level was 5.56 log10 copies/mL (range, 5--6.35 log10 copies/mL). The median alanine aminotransferase (ALT) level was 60.5 IU/L (range, 11--130 IU/L). The median HBV DNA level was 4.45 log10 copies/mL (range, 3.43--7.6 log10 copies/mL). Hepatitis B core antibody was isolated from 1 patient. Three patients were hepatitis B e antigen (HBeAg) positive. The patients received various combinations of antiretroviral therapies for HIV-1 infection, in addition to receiving lamivudine and tenofovir (2 patients received indinavir boosted with a low dose of ritonavir, 1 patient received saquinavir boosted with a low dose of ritonavir, 1 received abacavir, and 2 received efavirenz). All patients completed at least 96 weeks of treatment. By weeks 48 and 96, serum HBV DNA concentrations were undetectable by PCR (Roche Amplicor; lower limit of detection, <200 copies/mL) in 5 of 6 and in 6 of 6 patients, respectively. The decreased HBV DNA load was associated with an increased ALT level in 2 patients (ALT levels were increased 3.7-fold and 14.7-fold, respectively, by week 12). Antiretroviral treatment was maintained, and ALT levels returned to the normal range (normal value, <40 IU/L). Two patients cleared hepatitis B surface antigen (HBsAg) at week 36, and 1 patient (the patient with a history of liver decompensation) presented with HBsAg seroconversion (anti-HBs) at week 48. This patient did not present with a relapse of liver decompensation. Two patients presented with HBeAg seroconversion (anti-HBe) at weeks 36 and 56, respectively.
Hepatitis B is a potentially controllable disease that occurs very frequently among HIV-infected patients. The success of the use of lamivudine for the treatment of HBV infection has been hampered by the development of resistance during long-term use. The results of this prospective pilot study show that complete and sustained antiviral activity against wild-type HBV strains in HIV-1--infected patients was achieved during 96 weeks of combination therapy with lamivudine and tenofovir. The restoration of immunity (median CD4 lymphocyte count at week 96 was 355 cells/mm3 [range, 185--510 cells/mm3]) may also have played its part, contributing, in particular, to the high level of serological response (HBe seroconversion in 2 patients, HBs seroconversion in 1 patient, and loss of HBsAg in 2 patients). Therefore, the use of combination therapy (i.e., therapy with lamivudine and tenofovir) for HBV infection as part of HAART is very promising in the treatment of HIV/HBV coinfection. Although these results are very encouraging, further studies that include larger numbers of patients are needed.
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